Cong Nghe Bao Che Duoc Pham PDF

B Y T
CNG NGH
BO CH DC PHM
(DNG CHO O TO DC S I HC)
M S: .20.Z.09

NH XUT BN GIO DC
H NI 2007

Ch o bin son:
V KHOA HC V O TO B Y T
Ch bin:
PGS.TS. HONG MINH CHU
Page 1 of 255 Bo Y te - Cong nghe bao che duoc p
30/09/2009 file://C:\Windows\Temp\kgtcqomwpi\cong_nghe_bao_che_duoc_pham.htm
Tham gia bin son:
PGS. TS. HONG MINH CHU
PGS.TS. L QUAN NGHIM
TS. L HU
ThS. NGUYN NHT THNH
Tham gia t chc bn tho:
ThS. PH VN THM
TS. NGUYN MNH PHA

Li gii thiu

Thc hin mt s iu ca Lut Gio dc, B Gio dc v o to v B Y t ban hnh chng
trnh khung o to Dc s i hc. B Y t t chc bin son ti liu dy hc cc mn c s v
chuyn mn theo chng trnh trn nhm tng bc xy dng b sch t chun chuyn mn trong
cng tc o to nhn lc y t.
Sch CNG NGH BO CH DC PHM c bin son da trn chng trnh gio dc ca
Trng i hc Y Dc Thnh ph H Ch Minh trn c s chng trnh khung c ph duyt.
Sch c PGS.TS. Hong Minh Chu (Ch bin) v cc tc gi PGS.TS. L Quan Nghim, TS. L
Hu, ThS. Nguyn Nht Thnh bin son theo phng chm: Kin thc c bn, h thng; ni dung
chnh xc, khoa hc; cp nht cc tin b khoa hc, k thut hin i v thc tin Vit Nam.
Sch CNG NGH BO CH DC PHM c Hi ng chuyn mn thm nh sch v ti
liu dy hc chuyn ngnh o to Dc s i hc ca B Y t thm nh nm 2007. B Y t quyt
nh ban hnh ti liu dy hc t chun chuyn mn ca ngnh trong giai on hin nay. Trong thi
gian t 3 n 5 nm, sch phi c chnh l, b sung v cp nht.
B Y t chn thnh cm n cc tc gi v Hi ng chuyn mn thm nh gip hon thnh cun
Bn quyn thuc B Y t (V Khoa hc v o to)
874 2007/CXB/7 1918/GD M s: 7K727M7 DAI
sch; Cm n GS. L Quang Ton, PGS.TS. Hu Ngh c v phn bin, cun sch sm
hon thnh kp thi phc v cho cng tc o to nhn lc y t.
Ln u xut bn, chng ti mong nhn c kin ng gp ca ng nghip, cc bn sinh vin v
cc c gi ln xut bn sau sch c hon thin hn.

V KHOA HC V O TO B Y T

LI NI U

Thc hin ng li cng nghip ho v hin i ho t nc, cc ngnh cng ngh nc ta
v ang c nhiu tin b v cng hin ng k. Trong , cng ngh dc phm t s ng dng nhng
tin b khoa hc k thut ca nhiu ngnh nh cng ngh ho hc, cng ngh sinh hc, cng ngh c
kh, in, in t, tin hc... nghin cu pht trin, v ang c nhng ng gp nht nh. Tuy
nhin, cng ngh dc phm vn cn tn ti nhiu bt cp, cha p ng kp yu cu i hi ca kinh
t x hi hin nay v cho tng lai.
tin kp v ho nhp vi cc nc trong khu vc, ngoi mt quyt tm cao, i hi i ng khoa
hc c chuyn mn su, l thuyt i i vi thc t, mun vy phi ch trng cng tc o to. Chnh v
th, gp phn nh b vo s nghip cng nghip ho v hin i ho ngnh dc nc nh ni chung
v trong cng tc o to nhn lc dc ni ring, B mn Cng nghip Dc, Trng i hc Y Dc
Thnh ph H Ch Minh bin son cun Gio trnh cng ngh bo ch dc phm nhm cung cp
cho hc vin nhng thng tin, kin thc c s l thuyt chuyn khoa ct li nht, kt hp vi thc t i
hi ca ngnh dc.
Trong khun kh chng trnh khung ca B Y t, c s trao i, hi tho v chng trnh vi
Trng i hc Dc H Ni v tham kho chng trnh ca mt s trng nc ngoi c quan h
hp tc o to v nghin cu nh Trng i hc Mahidol Thi Lan, Trng i hc Paris Sud v
Trng i hc Bordeaux II CH Php, ni dung chnh ca gio trnh ny l cng ngh sn xut cc
dng thuc. Trc ht, dng thuc rn phn liu v dng thuc v (tit) trng c bin son.
Hy vng cun sch gp phn hu ch cho vic hc tp v nghin cu ca sinh vin dc, cng nh
bn c c nhu cu quan tm, tham kho khc.
Ln u tin xut bn, chc chn cun sch cn nhiu khim khuyt, cc tc gi mong nhn c s
gp ca bn ng nghip cng nh c gi ln ti bn sau c hon thin hn. Xin chn thnh
cm n.
TM. Cc tc gi

HNG DN S DNG SCH
Cun sch gm ba phn chnh, tng ng vi ba chng:
Chng 1: i cng v cng ngh bo ch dc phm cung cp cc thng tin, kin thc ti thiu
cn thit cho hc vin v nhng vn i cng chung i vi cng ngh bo ch dc phm, to c
s nng cao hiu bit, m rng tm nhn bao qut v l thuyt v thc t ca ngnh dc nc ta ni
ring v ca khu vc cng nh trn th gii ni chung. T , hc vin c th xc nh vai tr v nhim
v cho mnh trong hin ti v tng lai.
Chng 2: Cc qu trnh cng ngh c bn trong cng ngh bo ch dc phm gip cho hc vin
hiu bit v nhng qu trnh v thit b thng gp trong cng ngh bo ch thuc. Chng ny trnh
by cc nguyn l hot ng cng nh phm vi ng dng ca nhng trang thit b, my mc . Ngoi
ra, trong chng ny cng trnh by s lc v c l lm c s cho s tnh ton, la chn. T , cng
c hiu bit ca hc vin o to con ngi lm ch nhng trang thit b, my mc c s vt cht
hin i.
Chng 3: Cng ngh bo ch mt s dng thuc vi cng ngh mi kt hp ng dng nhng ph
gia truyn thng v hin i vo cc dng thuc vin nh vin nn, vin bao, vin nang. Bn cnh ,
dng thuc tim cng c trnh by trong chng ny.
Gio trnh ny c bin son theo khun mu chung ca Trng i hc Y Dc TP. H Ch
Minh, l s la chn, thng nht sau nhiu cuc hi tho v tp hun v chng trnh v vit gio trnh
trong d n nng cao cht lng dy v hc ca nh trng.
Trong mi chng cc bi c nh s th t tip theo bi ca chng trc. Trc khi nghin
cu hc tp hoc tham kho vo ni dung chnh ca bi, hc vin cn c mt ci nhn tng quan v xc
nh c mc tiu ca mnh vi mc tiu ca bi. thc hin mc tiu , cn phi c nhng ni
dung chnh vit trong sch, bng cch bm st mc lc v dn bi, hc vin s nhn ra c ni dung
ca bi cn c hay tham kho.
Sau qu trnh hc tp, nghin cu, hc vin c th t kim tra nh gi (lng gi) kt qu tip thu
nh phn cu hi lng gi c ghi cui mi bi.
Vi cch lm vic, hc tp, nghin cu nghim tc, hy vng s em li hiu qu xng ng cho hc
vin lm nn tng cho s vn dng sng to vo thc tin ngnh ngh.
CC TC GI

Ch bin
Hong Minh Chu
BNG NHNG CH VIT TT

Bi 1
S LC V S RA I V PHT TRIN
CNG NGH BO CH DC PHM
CND
SXT
CNBC
SXDP
CNHH
CNHD
CNSH
CNKS
HTCL
KTCL
HTBCL
THTSXT
CNBCDP
GPs/GxP
GMP
GLP
GSP
ISO
SOP
WHO
ASEAN
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Cng ngh dc
Sn xut thuc
Cng ngh bo ch
Sn xut dc phm
Cng ngh ho hc
Cng ngh ho dc
Cng ngh sinh hc
Cng ngh khng sinh
H thng cht lng
Kim tra cht lng
H thng m bo cht lng
Thc hnh tt sn xut thuc
Cng ngh bo ch dc phm
Good Practices Nhng thc hnh tt (GMP, GLP, GSP, v.v)
Good Manufacturing Practices Thc hnh tt sn xut thuc
Good Laboratory Practices Thc hnh tt phng kim nghim
Good Storage Practices Thc hnh tt bo qun thuc
International Standard Organization T chc tiu chun quc t
Standard Operational Procedures Quy trnh thao tc chun
World Health Organization T chc Y t Th gii
Hip hi cc nc ng Nam
CHNG 1
I CNG V CNG NGH BO CH DC
PHM

1.1. S ra i ca cng ngh bo ch dc
Thuc lun l mt nhu cu khng th thiu c trong i sng con ngi. Cng nh mi ngnh
khc, thuc i hi mt nn sn xut ngy cng cao v pht trin theo s pht trin v tin b ca loi
ngi.
Thi tin s, loi ngi bit dng thuc t thin nhin nh cy, c, l, thn, r, v cy cha
bnh, chng li bnh tt v sinh tn. Khi , ngi ta dng nhng nguyn liu cn ti, hoc c th phi
kh dnh. Dn dn, ngi ta bit dng nc thm t, ri bit un vi nc (sc) ly nc sc
dng l dng bo ch th s u tin ca dc phm.
Khi loi ngi bit ln men mt s thc vt cha bt, ng, ri bit ct ra ru (khong 1000 nm
trc cng nguyn), th cng t mt dng thuc th hai xut hin. l ru thuc, Ngnh bo
ch thuc cng ngh bo ch dc phm xut hin nh vy, t nhng dng th s n gin ban u
nh nc sc, ru thuc, cao thuc,
Tri qua my ngn nm lch s pht trin, tin b ca loi ngi, cng vi nhng cuc Cch mng
khoa hc k thut cng nh nhu cu ngy cng gia tng ca con ngi v phng v cha bnh, k thut
sn xut thuc cng ngy cng pht trin vi nhng dng thuc tinh t hn, phc tp hn. C th l cc
dng thuc vin, vin nn, vin bao, vin nang, thuc tc dng ko di, thuc tim, dch truyn,
l lch s ra i, tn ti v pht trin ca cng ngh bo ch cc dng thuc ni ring v ca nn
sn xut thuc ni chung.
MC TIU
1. Trnh by c s cn thit ca cng ngh bo ch dc phm.
2. K ra v phn tch c nhng yu t quan trng thc y s pht trin nn cng ngh bo
ch dc phm (yu t dn s, yu t bnh tt, yu t KHKTCN).
3. Trnh by c hai vai tr quan trng ca cng ngh dc phm sn xut thuc.
4. Phc ha c mt khung cnh sn xut thuc cha bnh Vit Nam trong cc thi k lch s
trc v sau nm 1975.

S 1.1. V tr, vai tr ca cng ngh bo ch dc phm i vi sc khe con ngi
1.2. S pht trin tt yu ca cng ngh bo ch dc phm
S pht trin ca cng ngh bo ch dc phm i lin vi s pht trin v tin b chung ca nhn
loi, n p ng nhu cu v thuc phng, chn on v cha bnh ngy cng gia tng ca ton cu.
Nhng yu t quan trng thc y cng ngh bo ch pht trin l:
* S gia tng dn s
Theo qu dn s Lin Hip Quc (UNFPA) cng b trong nhng nm gn y dn s th gii c s
tng vt, mang tnh cht bng n.
Mt khi dn s tng, nhu cu v thuc cng phi tng theo. Mc s dng thuc bnh qun u
ngi, c 10 nm li tng gp i. Vit Nam, ch trong 5 nm, t 1990 1995 mc s dng thuc
tng gp 10 ln. (Tuy nhin, trn th gii, mc tiu th ang c s chnh lch ln gia cc nc pht
trin v cc nc ang pht trin. Ngi dn cc nc cng nghip s dng dc phm bnh qun gp
30 ln nc ang pht trin. tng quc gia cng c tnh trng tng t v thc trng ngi dng
thuc thnh th v nng thn).
* S gia tng v bnh tt
Chng loi bnh tng, bnh ngy cng nguy him hn do vi trng khng thuc, do iu tr khng
ng phc hoc khng thuc, do thin tai v nhng l do khc V d bnh st rt, bnh lao vn
cn l cn bnh e do hng triu ngi trn th gii. Cn bnh th k AIDS, mi him ho ca ton cu
v cc bnh do virus khc.
* S pht trin ca cc ngnh KHCN khc: Cng nghip dc da trn s pht trin ca cng
nghip ho dc (bao trm l cng nghip ho hc), sn xut nguyn liu cung cp cho cng ngh bo
ch cc dng thuc. Cng nghip ho dc c th i t tng hp ho hc ra cc cht hoc chit tch cc
cht tinh khit t nguyn liu thin nhin, cy, con (thc vt, ng vt). S pht trin ca cng ngh bo
ch thuc cn c b tr bi s cung cp nguyn liu ngy cng phong ph ca cng nghip thuc
khng sinh v cng nghip sinh hc. Bn cnh , Cng ngh bo ch cc dng thuc cn c s h
tr tch cc ca tin b khoa hc k thut t nhiu ngnh, nh in t, c kh, ho hc
* Li nhun cng l mt ng c thc y cng ngh bo ch thuc pht trin, ng thi ng
gp tch cc cho nn kinh t x hi
i i vi vai tr sn xut, cung ng thuc cho y t phc v cng tc chm sc v bo v sc khe
con ngi, cng ngh bo ch thuc cn ng gp mt phn khng nh v tch cc cho nn kinh t x
hi.
1.3. Vi nt v tnh hnh bo ch thuc Vit Nam
Trc Cch mng thng Tm nm 1945: Cha c sn xut cng nghip, ch yu l ngun t Php
quc, c chng l pha ch theo n, c gng bo ch mt vi dng thuc m, thuc nc, vi
phng tin hon ton th cng cc bnh vin hoc hiu thuc t nhn, tnh cht hon ton l thuc.
Sau Cch mng thng Tm nm 1945, thi k khng chin chng thc dn Php (19451954):
p ng yu cu ca chin tranh v quc, cng ngh bo ch thuc lm ra nhng loi thuc phc v
chin trng, cc loi thuc thng thng cho nhn dn nh thuc cm, st, ho, tiu chy,, mt vi
vaccin c bn, thuc st rt, Nhng xng bo ch mang tnh chuyn nghip nh Xng Qun dc
XF14, LK10, LK34, LK5, ln lt ra i. Tuy c s trang thit b vn cn rt th s, t to, sn xut
tiu th cng, nhng y chnh l tin cho nn sn xut thuc mang tnh cng nghip sau ny. Thi
gian ny nc ta sn xut ra c mt s thuc nh Calci chlorid dc dng pha tim, Ether m,
Chloroform m, chit c Long no, Morphin, Strychnin, Cafein pha tim,
Thi k 19551975: Sau hip nh Geneve 1954, t nc tm chia lm hai min:
Min Bc hon ton gii phng, yu cu t ra cho ton ngnh l bo m nhng thuc ch yu cho
nhn dn, phn u sn xut trong nc nhng th thuc thng thng nht, thng nht tn dc v
ng dc. C s tp trung u tin c quy m ln, c kh ho, thit b tng i hin i lc by gi
l X nghip Dc phm Trung ng 1 (XNDPTW1), X nghip Dc phm Trung ng 2
(XNDPTW2), v bt u xy dng x nghip a phng cc tnh, phn u cc tnh thnh u c x
nghip dc phm (XNDP) xy dng b mn Cng nghip Dc ti Trng i hc Dc H Ni.
Min Nam cn nm trong ch thc dn kiu mi, cng nghip dc pht trin theo li t bn, c
nhng c s bo ch sn xut ln, c thit b hin i, nhng cng c nhiu c s sn xut th cng,
thit b chp v, Vo giai on ny, c khong trn 120 vin bo ch ln nh, nhng nguyn vt liu
hon ton ph thuc nc ngoi.
T sau 1975: Nc nh thng nht, ngnh Dc thng nht ch o, phng hng t Nam ti Bc,
tn dng mi c s vt cht, trang thit b bo ch sn xut tt c nhng thuc no c th sn xut c
vi mi ngun nguyn liu c th c c. Pha Nam tp hp v thnh lp XNDPTW 21, 22, 23, 24,
25, 26 v Lin vin bo ch 7. Sau sp xp li nh sau: XNDPTW 24, 25, 26 mt s x nghip thuc
a phng qun l nh XNDP 29, XNDP 32, XN Mebiphar, Pha Bc, cc XNDPTW1,
XNDPTW2, XNDPTW3, v mi tnh, thnh hu ht u c cc c s sn xut thuc ln, nh, Ch
trng xy dng ngnh dc tin ln chnh quy hin i cng nh Chnh sch quc gia v thuc Vit
Nam (1996) ch ra: M rng ging dy cc Trng i hc, xy dng v cng c i ng cn b,
c i hc nc ngoi, B Y t cng quyt nh thnh lp B mn Cng nghip Dc ti trng
i hc Y Dc TP. H Ch Minh (Quyt nh s 1899/BYTQ).
GMP c cp ti t 1984, bng nhiu cuc hi tho, tp hun v GMP.
Chnh sch quc gia v thuc c Chnh ph ban hnh t 2061996, theo c yu cu Cng
nghip Dc phi cung ng 70% nhu cu thuc cho nhn dn trong nc, phi phn u t tiu
chun GMP, ban hnh Quyt nh ca B Y t s 1516 ngy 991996 v vic trin khai p dng cc
nguyn tc tiu chun GMP ca Hip hi cc nc ng Nam , gi tt l ASEAN GMP, v Thng t
hng dn thc hin vic trin khai p dng cc nguyn tc ASEAN GMP ca B Y t s 12/BYTTT
ngy 1291996. Tt c cc doanh nghip sn xut dc phm phi GMP ho chm nht l vo nm
2005. T 2005 p dng WHO GMP.
T nhng nh hng ln v c bn ca chnh sch thuc quc gia, vi nhng i hi bc xc ca
ngnh Dc, nc ta xy dng quy hoch tng th u t pht trin ngnh Dc Vit Nam thi k
1996 2010, bao gm:
1. Nghin cu quy hoch pht trin cng nghip ho dc giai on 1996 2010
2. Nghin cu quy hoch u t pht trin cng nghip khng sinh
3. Quy hoch sn xut, pht trin dc liu v cc vng dc liu Vit Nam
4. Quy hoch sn xut, pht trin cng nghip bao b dc giai on 1996 2010
5. Quy hoch sn xut, pht trin cng nghip bo ch giai on 1996 2010
6. Quy hoch sn xut, pht trin v phn b cng nghip dc giai on 1996 2010
7. .
Nhn chung, trong mt thi gian kh di, t c ch bao cp chuyn sang c ch th trng, cng
ngh bo ch dc phm ni ring v cng nghip dc Vit Nam ni chung cn nhiu lng tng, mc
d cng c nhng ng gp nht nh, nhng hu nh khng c mt chin lc lu di. n nay, ngnh
Dc c nhng nh hng chin lc pht trin, m ra l trnh pht trin ca cng ngh bo ch
dc phm, phc v c lc nhu cu v thuc trong nc v xut khu.

TI LIU THAM KHO
1. L Quang Ton, KT ho dc, NXB Y hc H Ni, 1971.
2. Hong nh Cu, Y X hi hc Bi ging CK2 H Dc H Ni, 1985.
3. B Y t, Chnh sch Quc gia v thuc, H Ni, 1996.
4. B Y t, Chin lc pht trin KHCN ngnh Y t n nm 2020, H Ni, 1998.

CU HI LNG GI * TR LI NGN:
1. Yu t thc y s pht trin cng ngh bo ch dc phm
a) S gia tng dn s b)
c) S pht trin ca KH CN d)
2. S biu din vai tr CND trong s nghip Y t, bo v v chm sc sc kho con ngi:

a) b)
c) d) ...
3. Vi nt v tnh hnh sn xut thuc Vit Nam (ghi ngn gn mt n hai dng)
a) Trc Cch mng thng Tm 1945:
b) Sau Cch mng thng Tm 1945 (Khng chin chng thc dn Php):
c) Thi k 1955 1975:
d) T sau 1975:

Bi 2
QU TRNH NGHIN CU,
BO CH SN XUT THUC RA TH TRNG
2.1. Qu trnh nghin cu, bo ch sn xut thuc mi
MC TIU
1. V li c v gii thch s tng qut qu trnh nghin cu mt thuc mi ra th trng.
2. Nu c mc tiu ca giai on nghin cu, bo ch v giai on sn xut.
3. Trnh by c nhng yu cu cn thit xy dng mt cng thc bo ch thuc.
4. K c 4 ni dung chnh ca mt h s xin php sn xut thuc v cc ni dung chnh trong
h s dc phm.
5. Trnh by c nhng bc c bn nghin cu, bo ch sn xut mt thuc generic ra th
trng.
6. K c tm tt cc bc tin hnh xy dng tiu chun mt thuc generic.
2.1.1. S tng qut
C th tng qut ho qu trnh nghin cu, bo ch sn xut mt thuc mi ra th trng nh sau:

S 2.1. S tng qut qu trnh nghin cu sn xut mt thuc mi.
Ghi ch: NVL: Nguyn vt liu: CPT: Ch phm thuc ; SXTNM: Sn xut thuc nguyn mu;
NC(CT,QT): Nghin cu (Cng thc, Quy trnh); SXCN: Sn xut cng nghip.
2.1.2. Giai on nghin cu, bo ch thuc nguyn mu
Mc tiu ca giai on ny l tm ra c mt cng thc bo ch sn xut tt nht, ph hp vi
nhng iu kin kinh t k thut, t bo ch thuc nguyn mu th lm sng v xin php sn
xut a ra th trng.
Ngi sn xut ni chung, ngi dc s ni ring lun lun c gng nghin cu sn xut ra nhng
thuc c cht lng, hiu qu, an ton. Mun vy, phi xem xt rt k lng nhng thnh t ca cht
lng. Nhng thnh t c rt nhiu. i vi mt thuc mi, a ra c th trng, cn phi c s
nghin cu, la chn:
ng a thuc vo c th (ng s dng).
Dng bo ch thch hp.
T dc v cht ph gia.
Nguyn liu bao b ng gi.
Quy trnh sn xut.
Kim tra.
Quy trnh ng gi, bo qun...
S la chn khng th thc hin c nu thiu s hiu bit v hot cht cng nh ton b nhng g
v kh nng, lin quan n hot cht. Trong sn xut thuc, vic xy dng cng thc cho mt dng bo
ch ca mt thuc mi cha hot cht c hot tnh tr liu l rt quan trng. xy dng cng thc ny
phi c s kt hp cht ch gia nhng c s nghin cu v pht trin sn xut vi nhng phng th
nghim kim tra. Trc ht phi hiu bit v hot cht, tip l xy dng c cng thc cho dng
bo ch sn xut sau ny.
2.1.2.1. Nhng hiu bit v hot cht
Mun xy dng c cng thc cho mt thuc mi vi hot cht c tnh tr liu, iu quan tm u
tin, nh l im xut pht tin hnh nhng cng vic v sau, l hot cht (dc cht). Hot cht
l i tng nghin cu ca nhiu nh khoa hc: ho hc, c cht hc v dc l hc,... Nh nghin
cu bo ch sn xut thuc phi xem xt rt ra nhng nhn nh, nhng mc tiu quan st c c
th s dng vo cng vic nghin cu ca mnh. Nhng tnh cht ho l ca hot cht cn c bit r
nh trnh by trong bng 2.1.
Bng 2.1. Nhng tnh cht ca hot cht cn bit chc chn
trc khi cp nghin cu mt dng ch phm
a) Tnh cht vt l
Tnh tan ca hot cht l mt thuc tnh rt quan trng. Phi hiu bit chc chn v s ho tan trong
nc ca hot cht, bi v n s cho hng la chn dng thuc s dng (dng a vo c th) v n
ng vai tr ln trong tnh sinh kh dng. Quan trng hn na l nhng s hiu bit v kh nng ho tan
ca hot cht trong nc nhng pH khc nhau v phi bit n phn phi nh th no ty thuc vo pH
hay ty thuc vo s tham gia ca hai pha: nc v du.
b) Tnh cht ho hc
Tnh cht ho hc rt quan trng trong nghin cu n nh ca thuc.
Phi bit hot cht chu nh hng ca nhit khc nhau nh th no.
Phi bit nh hng ca m ra sao.
nh hng ca oxy khng kh.
nh hng ca nh sng,...
V phi bit c sn phm phn hy cui cng c th xc nh sau nhng th nghim v s n
nh, xc nh tui th hay thi hn dng thuc.
bit c nhng iu phi tin hnh th nghim trong nhng iu kin nhit , m, nh
sng v c oxy, t d on c gii hn s dng thuc (tui th ca thuc) trong iu kin bo
qun bnh thng trn th trng.
Mt cng vic nghin cu rt phc tp khc na l nhng nghin cu nhn bit nhng tng k ca
Tnh cht ho l S phn ca hot cht trong c th
Tnh cht cm quan
Tnh cht vt l: Kh nng ho tan
Tnh cht ho hc:
Thuc v dc
+ S phn phi
+ Sinh chuyn ho
+ Thi tr
Hot tnh tr liu (tc dng iu tr)
+ Ni tc dng
+ C ch
+ Tc dng ph
Sinh kh dng
Tnh n nh
v
Tng k

Nhit
m
Oxy khng kh
nh sng
Cc tc nhn khc
hot cht vi nhng thnh phn khc trong thuc v hot tnh ca n trong mi trng sinh hc.
c) S phn ca hot cht trong c th
Nhng yu t lin quan ti s phn ca hot cht trong c th thng c kho st bi cc nh
nghin cu dc l v hon tt bi cc thy thuc lm sng.
Nghin cu dc ng hc, trc tin ch ra cho chng ta v s phn phi ca hot cht, sinh
chuyn ho trong c th, ri s thi tr (thanh thi) ca n.
gip cho tc dng iu tr mt cch hu hiu, chng ta phi c gng tm hiu, bit nhiu v kh
nng v ni tc dng, c ch tc dng ca hot cht.
Mt nghin cu khng th thiu l gii hn tr liu, ngha l tm ra c khong cch gia liu
iu tr v liu m xut hin tc dng ph hay c hi.
Nh bo ch, sn xut phi nghin cu bit hot cht xm nhp vo c th nh th no, trc
ht phi nghin cu sinh kh dng ca n.
Trc khi nghin cu cng thc, cn c mt d kin v cch thc thc hin, nhm mc tiu t
c mt m hnh ti u sinh kh dng xc nh. Nhng yu t mong mun l:
S thm ko di trong c th.
Xc nh nhng nh (hp thu) nng trong mu.
2.1.2.2. Cng thc
Nghin cu xy dng (thit lp) cng thc cho mt thuc mi, nh bo ch sn xut thuc thng
phi quan tm ti: hot cht, ng a thuc vo c th, dng ch phm, nhng t dc, bao b ng
gi, quy trnh sn xut v kim tra.
a) Hot cht c th tn ti nhiu dng khc nhau. S la chn ty thuc vo cch dng v nhng
nghin cu v s n nh, ho tan v sinh kh dng ca thuc.
b) ng a thuc vo c th
La chn ng a thuc vo c th ph thuc:
Sinh kh dng ca hot cht.
Tc tc dng mong mun, thi gian iu tr v s liu trong ngy.
Loi bnh nhn nhng la tui v th trng khc nhau (s sinh, tr em, ngi ln, ngi gi,...)
cng nh tnh trng, bt u hay ti pht, nh hay bnh vin, iu tr lu ng hay khng,...
ng ung l ng thng dng nht, p dng c cho nhiu hot cht.
c) Dng thuc, la chn dng ch phm ty thuc vo ng dng thuc. Mt s dng ch phm
thng c nghin cu, s dng nh tm tt bng 2.2.
Bng 2.2. Dng ch phm thng dng
* ng ung:
Vin nn v vin nang l dng thuc rn phn liu thun tin cho bo qun, vn chuyn v iu tr
lu ng, thun tin cho sn xut cng nghip vi s lng ln.
Dng dung dch, hn dch nc cng l dng thuc thng dng. Di dng a liu, thun tin dng
cho mt s chng loi bnh nht nh.
* ng dng ngoi ung: Khng nhiu, thng l dng ng tim di dng dung dch nc.
Nu l bt tim, a phn c ng trong l, nhng c mt cu hi t ra cho vn bo qun.
d) Nhng cht t dc v nhng cht ph gia
i vi nhng cht ny, yu cu quan trng nht l tr v mt ho hc, khng c tc dng ph.
bit c ti a s m bo v mt cht t dc hoc cht ph gia no , ngi ta s phi nghin cu
thnh phn ho hc, tinh khit,...
S la chn ngy nay rt d dng nh da vo Dc in, hoc nhng ti liu nghin cu ca cc
nh nghin cu cng nghip dc tng hp, gm c: Tn, tn khoa hc, cng thc ho hc (cng thc
nguyn, cng thc cu to), trng lng phn t, tnh cht vt l,... V khng th thiu nhng kt qu
nghin cu ca nh bo ch sn xut thuc, chng hn nh trn chy ca n,...
Nh bo ch sn xut quan tm ti yu t nh hng n sinh kh dng ca thuc, la chn t dc
vi c tnh cho php, iu khin c tc gii phng hot cht. T , nh hng s dng t dc
vo nhng mc tiu nghin cu khc nhau hay vo nhng i tng c th khc nhau.
e) Bao b ng gi l mt thnh phn khng th thiu c ca mt dng thuc, c vai tr:
Bo v dc phm (Trnh cc s thay i ca kh hu, nh sng, cc ngun gy nhim v cc va
chm khi vn chuyn).
To gi tr thng mi cho mt hng (hp dn khch hng, tin s dng, xc nh v cung cp
nhng thng tin cn thit sm nht,...)
Cn ch nhng nguyn liu bao b ng gi tip xc trc tip vi thuc (bao b ng gi u tin),
cn la chn theo hng nhng nguyn liu c ghi trong danh mc ca cc Dc in.
Nhng th nghim quan trng cho php xc nh thi gian ko di s dng (hn dng) mt thuc
ng dng Dng thuc sn xut chnh
Ung Vin nn, nang, dung dch hay nh dch nc
Ngoi ng tiu ho Dung dch nc
ng trc trng n
ng sinh dc Vin nn, dung dch, trng,...
Mt Dung dch nc,...
O.R.L (Tai mi hng) Dung dch nc, bt,...
Ngoi da M, dung dch, thuc dn,
phi thc hin trong iu kin c bao b xc nh.
2.1.3. Giai on xin giy php sn xut thuc a ra th trng
H s hon chnh xin giy php sn xut thuc a ra th trng, yu cu c 4 phn chnh:
1. Phn thuc v dc (bo ch, phn tch, kim nghim,...)
2. Phn thuc v c tnh.
3. Phn thuc v dc l.
4. Phn thuc v lm sng.
H s dc thng gm c:
Thnh phn, s lng v cht lng.
M t quy trnh sn xut.
Kim tra nguyn liu u vo v bao b.
Kim tra trn sn phm trung gian, bn thnh phm v thnh phm.
M t nhng iu kin bo qun v cch dng.
Trng hp c bit cn c gii thch ngi dng c s la chn ng v chnh xc. Km theo h
s phi c nhng nghin cu v tnh n nh, v dc ng hc, sinh kh dng, phm vi iu tr cng
nh nhng iu lut bt buc v k thut v kinh t.
Mt im rt quan trng cn lu l nhng th nghim lm sng khng th lm li c theo li c.
Nhng th nghim trn ngi l hiu lc mt ln cho tt c vi nhng n v ca l thuc nguyn mu.
Theo thi quen (li c), mi l sn xut, nhng th nghim thay th bng nhng th nghim ho l cho
php xc nhn cht lng ca thuc.
H s lm theo Quy ch ng k thuc, ban hnh km theo quyt nh B Y t.
2.1.4. Giai on sn xut v kim tra
Mc tiu ca giai on ny l ti sn xut quy m cng nghip ra nhng thuc c cht lng ph
hp vi cht lng ca l nguyn mu (l ng k sn xut).
Ngoi ra, t c mc tiu trn, quy trnh sn xut cn phi la chn theo nhng mc tiu
nh, cng cn ty thuc vo c nguyn liu s dng.
Mi mt cng on phi c nhng thng s k thut quyt nh, thuc sn xut ra m bo cht
lng ton din. Mun vy cn phi kim tra cht ch, t nguyn liu u, sn phm trung gian, n sn
phm cui cng bng nhng thit b chnh xc c tin cy cao, c s thm nh,... (kim tra cht
lng).
Kim tra s ng nht gia cc l sn xut da trn tnh n nh ca thuc v trn tnh sinh kh
dng ca hot cht,...
Tm li giai on ny cn phi thc hin nghim ngt mi tiu chun, mi yu cu ca GMP nhm
m bo cht lng thuc n nh a ra th trng.
Qu trnh nghin cu mt thuc mi ra th trng i hi nhiu thi gian v kinh ph kh ln. Trc
y, k t khi bt u nghin cu tm ra c hot cht c tc dng n khi sn xut c thnh
phm bn ra th trng, thng phi mt 10 15 nm v tiu tn khong hng trm triu USD. Ngy
nay, thi gian ny c th rt ngn li.
2.2. Qu trnh nghin cu, bo ch sn xut mt thuc generic ra th trng
Thuc generic l mt thuc c cng thc ging nh thuc nguyn thy c quyn c mt hay
nhiu hng bo ch khc nhau sn xut khi tnh c quyn khai thc khng cn na.
Thc t, khi mt hng bo ch nghin cu thnh cng mt hot cht mi, cng hiu cao i vi mt
bnh no , th ch nhn xin ng k bn quyn sng ch trnh b sao chp, v c khi h phi b ra
c trm triu USD M trong nghin cu, nht l vi nhng khng sinh. Nhng sau mt thi gian sn
xut c quyn (v d nh 17 nm Php, 15 nm M), thuc y tr thnh cng cng v tt c cc
hng bo ch trn th gii u c th sn xut m khng phi tr bn quyn sng ch.
Qu trnh nghin cu sn xut mt thuc generic ra th trng khng mt nhiu thi gian v tn km
bng nghin cu sn xut mt thuc mi, c th qua nhng bc nh sau.
2.2.1. Nghin cu tm kim, la chn cng thc ti u
Trc ht, nh nghin cu phi c mt tng, a ra mt d kin mc tiu t ti: dng ch phm,
hnh thc, mu m, tiu chun, v.v
Thc hin tng , cn phi:
Thu thp ti liu xung quanh mc tiu: ti liu trong nc, nc ngoi, v hot cht, v dng ch
phm cha hot cht , v cc cht ph gia, v cc bao b ch phm ,... tt c cc ti liu c th phc
v c nhiu nht cho mc tiu nghin cu ca mnh.
Tm hiu th trng, quan st thc t, nhng ch phm c,... trnh nhi li, t hc tp,
cng c tng v d kin,...
Tm kim ngun nguyn vt liu cho sn xut c cht lng, s lng n nh, gi c ph hp,...
v ph hp vi iu kin kinh t k thut hin c.
D kin cng thc da trn nhng cng thc truyn thng/kinh in hoc nhng ti liu mi nht.
Th nghim trn cc cng thc la chn ra mt cng thc tt nht, cc thng s k thut ti u
nhm m bo cht lng thuc ph hp vi cc iu kin:
+ K thut: Cht lng n nh vi ngun nguyn vt liu hin c, c th sn xut c lu di.
+ V y hc: Gii p c nhng cu hi:
1) Thuc c tc dng khng? 2) C tc dng ph khng? 3) Dung np tt khng? 4) Thuc c tnh
sinh kh dng,... Ch yu phi kim tra kh nng gii phng hot cht ( ho tan) ca thuc sn xut ra
theo cng thc , v an ton ca thuc.
+ V th trng: Ngi tiu dng chp nhn dng ch phm, s dng thun tin, d dng, khng
nhm ln,...
+ V kinh t: Gi c thch hp, hiu qu kinh t,...
2.2.2. Th nghim v xy dng tiu chun ch phm
Sau khi la chn c mt cng thc tt nht ph hp vi nhng iu kin kinh t k thut, s
sn xut th nghim t n s n nh v cht lng v sn xut ra thuc nguyn mu (thuc ny s
gi km theo h s xin giy php ng k sn xut), v ng thi, tin hnh xy dng tiu chun.
Xy dng tiu chun ch phm:
Yu cu k thut
Cng thc: phi ghi y tn hot cht, t dc,... s lng v cht lng (theo tiu chun no,...).
Nguyn vt liu: s lng, cht lng,... (ghi theo hng dn GMP).
Phng php th: Nhn xt cm quan.
+ nh tnh.
+ nh lng.
Thuyt minh tiu chun
+ nh tnh: phng php, tiu chun, cch tin hnh,...
+ nh lng: phng php, m t cch tin hnh, kt qu,...
Ch : chnh xc, tin cy ca phng php
n nh ca thuc:
Phng php xc nh n nh. M t cch tin hnh. Kt qu, x l v bin lun,
Kt lun: Phi khng nh nhng cng vic thc hin l c tnh khoa hc v chnh xc vi tin cy
cao, c x l thng k hay theo phn mm no ca my tnh,... Ch km theo nhng ti liu gc
(photo), cc bn tnh ton c th...
2.2.3. Gi mu n c quan kim nghim
Gi mu thuc n c quan kim nghim, km theo cc ti liu lin quan n dc phm , bao
gm:
Nhng tiu chun xy dng v ngh.
Nhng h s ti liu cn thit km theo (theo yu cu ca mt hng).
2.2.4. Xy dng quy trnh sn xut (son tho)
Thc hin theo mu hng dn ca c quan qun l (Cc Dc B Y t).
2.2.5. Tp hp, son tho h s xin ng k sn xut
Theo iu khon quy nh i vi thuc sn xut trong nc, trong bn Quy ch ng k thuc ban
hnh km theo quyt nh ca B Y t.
2.2.6. Sn xut v kim tra cht lng
Sn xut v kim tra cht lng thc hin theo GMP.

TI LIU THAM KHO
1. Hong Minh Chu, Sn xut Thuc Cng nghip Dc, Bi ging cho Dc s v CT3, i hc
Y Dc, TP.HCM, 1997).
2. LE HIR, Abrgs de Pharmacie galenique, R.F.Paris, 2000.
3. Quy ch ng k thuc ban hnh km theo quyt nh ca B Y t.

CU HI LNG GI * TR LI NGN:
1. Qu trnh nghin cu sn xut thuc mi ra th trng:
S tng qut: (V li s xng c)
2. Mc tiu ca giai on nghin cu v sn xut th ra thuc nguyn mu: Mc tiu ca giai on
ny l nghin cu tm ra c (a) tt nht (ph hp iu kin kinh t x hi), t (b)
a th lm sng
3. giai on nghin cu v sn xut th thuc nguyn mu, nhng thnh t quan trng cn nghin
cu la chn:
a)
b) ng a thuc vo c th (ng s dng)
c)
d) Nhng cht ph gia (t dc)
d)
f) Quy trnh sn xut
g)
h) Quy trnh ng gi
i)
4. Nhng hiu bit v hot cht (3 ghi nh quan trng)
a) Tnh cht (a)
b) Tnh cht (b)
c) Tnh cht (c)
5. Trong tnh cht vt l ca hot cht phi bit chc chn:
a) Tnh (a)
b) Hiu bit v kh nng (b) nhng pH khc nhau
6. Cc hiu bit v nhng nh hng ln hot cht gip cho s nghin cu n nh thuc l:
nh hng ca nhit khc nhau
a) nh hng ca (a)
nh hng ca oxy khng kh
b) nh hng ca (b)
7. Gip cho nghin cu n nh thuc cn:
a) Phi bit sn phm (a)........ cui cng
b) Bit nhng (b) ca hot cht vi nhng thnh phn
khc trong thuc
8. S phn ca thuc trong c th Nhng nghin cu lin quan:
a) Nghin cu (a)
b) Ni tc dng,(b)... tc dng
c) Gii hn (c), ngha l tm ra c khong cch gia liu
iu tr v liu m xut hin tc dng ph hay c hi.
9. Nh bo ch sn xut phi nghin cu bit hot cht
Xm nhp (a) nh th no, trc ht phi nghin cu....... (b) ca thuc.
10. Nghin cu thit lp mt cng thc cho thuc mi, nh bo ch sn xut thng quan tm n:
a) Hot cht
b) vo c th
c) Dng bo ch ch phm
d) Nhng cht
e) Bao b ng gi
f)
g) Kim tra

Bi 3
H THNG QUN L CHT LNG
CC GxP P DNG TRONG SN XUT DC PHM
MC TIU
1. Trnh by c mt s khi nim c bn v cc GxP (GMP, GLP, GSP), ISO; s cn thit,
mc tiu v vai tr trong cc c s sn xut thuc.
2. Gii thch c mi quan h m bo cht lng (BCL), GMP v kim tra cht lng
(KTCL).
3. Phn tch c 5 yu t, 3 nguyn tc v 10 yu cu c bn ca GxP.
4. K c 17 chuyn mc ca WHO GMP v phn tch tm tt theo 5 yu t v cc nguyn tc

CC KHI NIM C BN
1. CHT LNG
1.1. Khi nim v sn phm v cht lng ni chung
* Sn phm l kt qu ca cc hot ng v ca cc qu trnh ch nh v khng ch nh, gm sn
phm vt cht thun tu, phi vt cht, gm c dch v, phn cng v phn mm.
* Cht lng l mt tp hp cc c tnh vn c p ng cc yu cu (nhu cu hay mong i
c cng b, ngm hiu hay bt buc).
1.2. Cht lng thuc
L tng hp cc tnh cht c trng ca thuc, th hin mc ph hp nhng yu cu nh
trc trong iu kin xc nh v kinh t k thut x hi, c th hin bi cc yu cu sau y:
C hiu lc phng bnh, cha bnh.
Khng c hoc t c tc dng ph c hi.
n nh v cht lng trong thi gian xc nh.
Tin dng, d bo qun.
Hnh thc hp dn.
1.3. c im v yu cu v thuc
Thuc l hng ho c bit lun c hai mt li v hi.
Thuc l nhng dng bo ch c nhiu thnh phn to nn, c tc dng dc lc.
Thuc l mt loi sn phm c hm lng cht xm v cng ngh cao.
Cht lng thuc khng d dng nhn bit c bng cm quan.
Thuc phi gn lin vi thng tin v sn phm.
Yu cu: cht lng, hiu qu, an ton v kinh t.
2. QUN L CHT LNG l cc hot ng c phi hp nh hng v kim sot mt t chc
v cht lng. Vic nh hng v kim sot cht lng ni chung bao gm lp chnh sch cht lng
v mc tiu cht lng, hoch nh cht lng, kim sot cht lng, m bo cht lng v ci tin
cht lng
3. KIM SOT CHT LNG (QC) l s dng cc k thut phn tch v tin hnh cc hot ng
c bn ca cc GxP.
5. Lin h v k ra c mt s c s sn xut thuc Vit Nam vn dng cc GxP v t tiu
chun GMP (hoc c ba: GMP, GLP v GSP).
tho mn cc yu cu ca cht lng.
Kim sot cht lng nhm vo vic gim st qu trnh v loi tr cc nguyn nhn khng ph hp
tt c cc giai on thng qua vic nh gi cht lng so vi yu cu ra. Mt s hot ng ca
kim sot cht lng v m bo cht lng c mi quan h tng tc.
4. M BO CHT LNG (QA) l mt khi nim rng bao gm ton b cc vn ring l hay
tng hp nh hng n cht lng sn phm, k c cc nguyn liu. m bo cht lng l tng th
cc k hoch c thc hin nhm mc tiu m bo cc nguyn liu v cc dc phm t cht lng
yu cu s dng.
Ni cch khc, m bo cht lng l ton b k hoch, bao gm c GMP, c tin hnh theo trnh
t, m bo dc phm ph hp cng dng ca n.
5. MI TNG QUAN GIA M BO CHT LNG, GMP V KIM TRA CHT
LNG THUC
H thng m bo cht lng thuc l mt h thng bao trm tt c nhng yu t, nhng bin php
c thc hin nhm m bo cc thuc sn xut ra u t cht lng ng k. Nh vy h thng
ny c lin quan n tt c cc khu, cc giai on, t c nhn n tp th c nh hng n cht lng
thuc. H thng m bo cht lng thuc phi m bo rng:
* Sn phm c thit k phi m bo cc yu cu GMP, GLP, GSP.
* Cc thao tc v kim tra cht lng phi tun theo GMP (cc SOP).
* Trch nhim qun l phi c nu r trong phn m t cng vic (phn nh).
* Cn b tr cung ng v s dng ng nguyn liu, bao b.
* Kim tra nguyn liu u vo, sn phm trung gian, bn thnh phm, quy trnh sn xut.
* Thnh phm c pha ch ng cch v kim tra theo cc quy trnh nh (bo m sn xut v
kim tra cht lng trc khi xut xng).
* Sn phm ch c xut xng/bn khi c chng nhn ca ngi c thm quyn theo quy nh
trong giy php.
* C k hoch bo qun, phn phi v qun l sn phm duy tr cht lng trong thi gian hn
dng ca thuc.
* C mt quy trnh thanh tra/t thanh tra v cht lng thng xuyn nh gi c hiu qu v
tnh kh dng ca h thng m bo cht lng (t chc thc hin t thanh tra v gim st cht lng)
Tm li: H thng m bo cht lng c th c hnh dung biu din theo s 3.1 sau:

S 3.1. Mi quan h gia H thng m bo cht lng, GMP v kim tra cht lng

CC NGUYN TC THC HNH TT (GxP) P DNG
TRONG CC C S SN XUT THUC (CNDP SXT)
Thc hnh tt sn xut thuc GMP (Good Manufacturing Practice)
Thc hnh tt phng kim nghim thuc GLP (Good Laloratory Practice)
Thc hnh tt bo qun thuc GSP (Good Storage Practice)
1. NM YU T C BN CA CC GxP (CN GI 5 M)
Con ngi (Man M1)
Nguyn vt liu (Material M2)
Mi trng, c s sn xut (Millieu M3)
Trang thit b (Machine M4)
Ti liu quy trnh, phng php,... (Method M5)

S 3.2. Nm yu t c bn ca GxP
1.1. Con ngi (M1)
L mt trong nhng yu t quan trng hng u, i hi:
v s lng, tiu chun
C thc v thi quyt tm thc hin GMP
m bo c nhng yu t trn i vi con ngi, cn c s o to, c hun luyn thng
xuyn, c k hoch v chng trnh c th.
1.2. Nguyn vt liu (M2)
Ch c nguyn liu tt mi cho sn phm tt. Nguyn vt liu bao gm:
Hot cht, cc cht ph gia, t dc, nguyn vt liu bao b ng gi (ng gi trong, ng gi
ngoi),...
1.3. Mi trng, c s vt cht (M3)
a im, mi trng, thit k, xy dng ng chc nng,... m bo cp v sinh theo yu cu.
1.4. Trang thit b (M4)
Phi c trang b ph hp thc hnh tt theo yu cu: v s lng, chng loi, ng b,...
ng v vt liu, thit k, ch to, cht lng tt. t ng v tr, s dng thun tin, d v sinh, an
ton,...
1.5. Ti liu (quy trnh, phng php tin hnh,) (M5)
H thng ti liu ph hp theo tinh thn Vit ra nhng g lm, lm theo nhng g vit v cc
kt qu ghi vo h s, phi c y quy trnh, phng php tin hnh, kim tra, ni chung phi c
y cc ti liu thc hnh.
2. BA NGUYN TC C BN CA CC GxP
1. Vit nhng g cn lm (cc hng dn, quy trnh, thao tc chunSOP,)
2. Lm theo nhng g vit
3. Ghi kt qu vo h s (h s ho)
3. MI YU CU C BN CA CC GxP
1. Vit cc quy trnh (cc SOP)
2. Thc hin theo cc quy trnh
3. H s ho cng vic lm
4. Thm nh
5. S dng trang thit b thch hp
6. Bo tr trang thit b
7. Hun luyn, o to
8. Sch s, trt t, v sinh, ngn np
9. Cnh gic cht lng
10. T thanh tra.
4. SN PHM CA CC GxP
Sn phm ca GMP l thuc (dc phm) vi nhng yu cu: cht lng, hiu qu, an ton v
kinh t.
Sn phm ca GLP l nhng phiu kim nghim vi nhng yu cu: trung thc, khch quan, chnh
xc v tin cy.
Sn phm ca GSP l nhng hng ho vi 4 yu cu c bn: bo qun ng iu kin (yu cu ca
thuc), phn loi sp xp hp l (theo ng cc nguyn tc ba d, FIFO, FEFO), qun l cht ch h
thng (HSTL) v cht lng m bo (khng b bin i).
Sn phm ca c ba GPs l sn phm thuc tho mn ngi tiu dng.
5. NI DUNG C TH CA CC GxP
Vit Nam ang p dng WHO GMP, GLP v GSP do B Y t ban hnh.

THC HNH TT SN XUT THUC
(GOOD MANUFACTURING PRACTICE GMP)

1. M U
1.1. Yu cu khch quan v ch quan
* Nhu cu v thuc cng ngy cng tng:
V s lng:
+ Dn s ngy cng tng (theo qu dn s Lin hip quc UNFPA cng b nhng nm gn y
dn s th gii tng vt mang tnh cht bng n) nm 1987 th gii c 5 t ngi, 1998 c 6 t ngi,
theo d bo c ny n nm 2050 th gii s c 9,4 t ngi v 10,4 t vo nm 2100,... Vit Nam,
nm 1945 ta mi c 25 triu ng bo Nam Vit n 10/10/2002 theo thng k c 80 triu dn,...).
+ Bnh tt nhiu, cc bnh nhim khun, cc bnh ti pht,... cn bnh th k (HIV/AIDS), v cc
bnh do virus khc,
V cht lng, ngi tiu dng i hi (PIES): Tinh khit (P: Pure), ng (I: Correctly Identifed),
Hiu qu (E: Effective) v An ton (S: Safe).
* Nn sn xut thuc pht trin:
p ng nhu cu v thuc cho con ngi.
ng gp cho nn kinh t x hi.
ng dng nhng tin b k thut cng ngh mi ca cc ngnh nh: cng ngh ho dc, cng
ngh sinh hc, cng ngh cy thuc, cng ngh bao b v cc ngnh khc nh c kh, in t, tin hc,...
* Xu th hi nhp:
Xu th hng ti nn kinh t ton cu v xu th tiu chun ho, ng b ho cc lut l Quc t.
i vi thuc, vn cht lng l vn ton cu, c t ra mi quc gia, mi ni, mi lc. Mt
trong nhng h thng m bo cht lng c nhiu nc t ra v thi hnh l GMP.
* Vit Nam gia nhp khi ASEAN, tr thnh mt thnh vin ca WTO. hi nhp vo khi
ASEAN v Th gii, i vi ngnh Dc, B Y t ban hnh thng t s 12/BYT, ngy 12/9/1996 v
vic trin khai p dng nguyn tc, tiu chun ASEAN GMP, nhm mc ch tng bc a cng
nghip dc Vit Nam pht trin, nng cao cht lng thuc trong nc, phc v tt s nghip chm
sc sc khe nhn dn, to iu kin cho thuc Vit Nam ho nhp th trng thuc ca khu vc v th
gii... Phn u n ht ngy 31/12/2007, tt c cc c s sn xut thuc tn dc phi trin khai p
dng, t nguyn tc, tiu chun WHO GMP v n ht ngy 31/12/2010, tt c cc c s sn xut
thuc t dc liu phi t nguyn tc, tiu chun WHO GMP (theo quyt nh s 19 ngy 05/07/2005).
l mt yu cu cp thit ca ngnh Dc.
1.2. Gii thiu s lc GMP cc nc v khu vc
c nhiu nc ra v thc hin GMP t lu.
Hoa K l mt trong nhng quc gia u tin c gng qun l ngnh dc. Sau mt s s kin xy
ra lin quan ti sc khe con ngi, nm 1962, mt o lut v thc phm, thuc v m phm c C
quan qun l thc phm v dc phm Hoa K (FDA) thng qua, ra i nhng quy nh u tin v
GMP.
+ Nm 1963: GMP n bn ln th nht.
+ Nm 1975: Hng dn v thm nh ra i (sau v 11 ca t vong do thiu kim tra trong khi sn
xut thuc).
+ Nm 1976: Mt b GMP mi ra i, vi trng tm hng vo Thm nh v m bo cht lng
hn l kim tra cht lng.
+ Nm 1978: GMP n bn ln th hai.
+ Nm 1979: GMP tr thnh lut v yu cu cc nh sn xut phi c cc quy nh v thao tc chun
c ph duyt v cc h thng c thm nh.
+ Nm 1984, qua s kin Tylenol ngi ta phi xem xt li trong quy ch cc vn lin quan n
ng gi.
c: GMP n bn ln th nht t 1969.
Anh: + Nm 1971: GMP n bn ln th nht.
+ Nm 1977: GMP n bn ln th hai.
+ Nm 1983: GMP n bn ln th ba.
Php: Vn bn Thc hnh sn xut tt (Pratiques de Bonne Fabrication PBF) ban hnh u tin
vo 3/10/1978.
+ 1/10/1985 ban hnh ng ngha GMP.
+ Nm 1993 thc hin GMP EEC.
+ Nm 1995 BPF GMP xut bn ln th ba.
Cng ng chu u ECC: ban hnh ti liu hng dn v GMP chu u vo thng 1/1989.
T chc Y t th gii (WORLD HEALTH ORGANIZATION WHO):
* Nm 1967: ban hnh bn d tho Draft requirements for good manufacturing practice in the
manufacture and quality of drugs and pharmaceutical specialities.
* Nm 1968: ban hnh GMP nh l mt ph lc trong bo co ln th 22 ca WHO v sau c
a vo bn ph lc ca The International Pharmacopoeia. 1971.
* Nm 1969: ban hnh vn bn GMP nh l mt phn trong Certification Scheme on the Quality of
Pharmaceutical Products.
1975: chnh sa ban hnh li.
* Nm 1992: xut bn GMP c chnh sa v b sung. Xut bn Validation of analytical
procedures used in the examination of pharmaceutical materials.
* Nm 1999: xut bn Good manufacturing practices and inspection.
* Nm 2000: Guide to good manufacturing practice for medicinal plants.
* Nm 2003: xut bn ph lc 4 Good Manufacturing Practices for pharmaceuticals: main
principles trong lot bo co k thut ca WHO No.908.2003.
ASEAN: * 1984 xut bn u tin gm 2 phn.
* 1988 xut bn ln th hai.
* 1996 xut bn ln th ba.
Vit Nam: cp ti GMP t 1984 v t chc cc cuc hi tho, tp hun GMP vo nhng nm
tip sau 1987,... 1997,... ti H Ni, TP. H Ch Minh, Cn Th, v.v...
T 1996 bt u p dng ASEAN GMP. T nm 2005 p dng WHO GMP.
1.3. Mc tiu v vai tr ca GMP
Mc tiu ca GMP nhm m bo mt cch chc chn rng dc phm c sn xut ra mt cch
n nh, lun lun t cht lng nh nh sn (nh thuc nguyn mu ng k).
V tr v vai tr ca GMP l mt b phn ca cng tc nh gi cht lng nhm m bo cc sn
phm c sn xut v kim sot ng nht tiu chun cht lng ph hp vi mc ch s dng v
theo yu cu ca giy php lu hnh. Ni cch khc, GMP l mt yu t c bn ca m bo cht
lng, v n thc hin phng chm phng sai li hn cha sai li, to nim tin cho khch hng.
GMP l ton b nhng khuyn ngh cn thc hin cho php m bo cht lng ca mt thuc
xc nh trong iu kin tt nht. Nhng khuyn ngh ny m t nhng mc tiu khc nhau cn t ti
lin quan n cc ni dung nh t chc, con ngi, c s trang thit b,... cng nh cc cch kim tra
cn thit, kim tra t khu nguyn liu u vo n qu trnh sn xut, thnh phm, v.v... V cng ch ra
nhng phng tin cn thit m bo cht lng thuc a ra th trng
Theo Anh 1983, GMP l nhng hng dn nhm khuyn co cc bin php m cc nh sn xut nn
tun theo mi khi cn thit v ph hp, nhm m bo sn phm c tnh cht v cht lng nh
mong mun, t mc ch nh. Ni mt cch khc GMP gip cho nh sn xut: Sn xut ra nhng
thuc c cht lng n nh nh thuc ng k c cp giy php sn xut. Nhng thuc c cc
thuc tnh: Tinh khit (P), ng (I), hiu nghim (E) v an ton (S) (PIES).
1.4. im qua GMP ASEAN
Trn c s nm yu t v cc nguyn tc c bn ca GxP, ASEAN GMP c th ho ra 10 iu
khon v 4 ph lc nh sau:
+ 10 iu khon:
1. Cc iu khon chung 2. Nhn s
3. Nh xng 4. Thit b, dng c
5. Bin php v sinh v tiu chun v sinh 6. Sn xut
7. Kim tra cht lng 8. T thanh tra
9. X l khiu ni, thu hi v sn phm tr v. 10. Ti liu
+ 4 Ph lc l: 1/ Sn xut cc sn phm sinh hc.
2/ Sn xut cc cht kh Y hc.
3/ Sn xut bnh xt phn liu c p lc.
4/ Sn xut cc ch phm Y hc dn xut t mu ngi...
2. HNG DN THC HNH TT SN XUT THUC THEO KHUYN CO CA T
CHC Y T TH GII (WHO GMP WORLD HEALTH ORGANIZATION GOOD
MANUFACTURING PRACTICES)
Qua phn gii thiu, chng ta bit c cc nguyn tc chung, cc thut ng dng trong ti liu
ny v quan nim v qun l cht lng trong cng nghip dc. Trn c s nm yu t, nhng nguyn
tc v cc yu cu c bn ca GxP, WHO GMP ra nhng ni dung c th trong cc chng mc,
v d nh v con ngi ( mc 9, 10, 11: nhn s, o to, v sinh c nhn); v c s vt cht, nh
xng, mi trng c ghi mc 12; v my mc, trang thit b ghi mc 13; v nguyn vt liu
mc 14 (nguyn liu u vo, dc cht cc hot cht, t dc) v h s ti liu mc 15. GMP
WHO quan tm su sc ti sn xut v kim nghim theo hp ng c trnh by trong mc 2 v 7.
Thm nh qu trnh sn xut l vn d l l trong cc c s sn xut thuc, c ra mc 4 v
v sinh cht ch mc 3 v 11. C th theo trnh t sau:
WHO GMP Ni dung 17 iu khon
1. m bo cht lng (quality assurance)
2. Thc hnh tt sn xut thuc (GMP)
3. V sinh v iu kin v sinh (sanitation and hygiene)
4. nh gi v thm nh (qualification and validation)
5. Khiu ni (complaint)
6. Thu hi sn phm (product recalls)
7. Sn xut v kim nghim theo hp ng (contract production and analysis)
8. T thanh tra v thanh tra cht lng (selfinspection and quality audits)
9. Nhn s (personnel)
10. o to (training)
11. V sinh c nhn (personal hygiene)
12. Nh xng (premises)
13. Thit b (equipment)
14. Nguyn vt liu (materials)
15. H s ti liu (documentation)
16. Thc hnh tt trong sn xut thuc (good practices in production)
17. Thc hnh tt kim nghim (good practices in quality control)
Ngoi ra, cn c phn hng dn ph c iu chnh b sung nhm pht trin thm cc hng
dn mi trong tng lai. V d: GMP Nhng dc phm chuyn bit nh dc phm tit trng, cc
sinh phm, dc phm th lm sng trn ngi, dc tho. Tt c cc ti liu ny c th truy cp trn
trang web WHO:
(http.www.who.int/medicines/organization/qsm/activities/qualityassurance/gmpcover/htmlo).
2.1. m bo cht lng
2.1.1. m bo cht lng: nh trnh by phn Cc khi nim c bn
2.1.2. H thng m bo cht lng ph hp cho sn xut dc phm: nh trnh by phn Cc khi
nim c bn
2.1.3. Nh sn xut phi chu trch nhim v cht lng sn phm m bo l chng ph hp vi
mc ch s dng, tun theo cc quy nh trong giy php lu hnh. Mc tiu cht lng c thc hin
ph thuc vo trch nhim cc nh qun l cao cp, cc phng ban trong cng ty, nh cung cp, phn
phi. C h thng m bo cht lng kt hp c GMP ln kim tra cht lng. Hot ng H thng
m bo cht lng phi c lu tr h s y v theo di. C nhn vin, c s vt cht nh
xng, my mc, trang thit b ph hp.
2.2. Thc hnh tt sn xut thuc (GMP)
GMP l mt phn ca m bo cht lng, gip m bo rng sn phm c sn xut ng nht
v kim sot theo ng cc tiu chun cht lng ph hp vi mc ch s dng ca chng, cng nh
theo ng cc quy nh ca giy php lu hnh.
Cc nguyn tc trong GMP trc ht hng ti vic gim thiu cc nguy c d xy ra trong qu
trnh sn xut dc phm (hai loi nguy c: nhim cho, ln do dn nhn sai) mang tnh phng nga. 10
yu cu/yu t c bn trong GMP phi c tn trng (xem thm phn Cc khi nim c bn).
2.3. Nguyn tc v sinh v thc hnh v sinh (NTVS v THVS)
Cc nguyn tc v thc hnh v sinh phi c thc hin nghim ngt trong qu trnh sn xut.
Phm vi thc hin: nhn vin, nh xng, my mc thit b, nguyn liu u vo, bt k th g c
th l ngun ly nhim i vi sn phm. C chng trnh tng th (trnh by chi tit tng mc, nh
mc 11: v sinh c nhn, mc 12: nh xng).
V d:
Bng 3.1. Tiu chun cp v sinh (ca WHO v ASEAN)
2.4. Thm nh
Thm nh l mt phn c bn trong GMP v cn phi c thc hin theo ng cng nh.
Cn lp ra cc quy trnh thao tc (SOP) v quy trnh sn xut da trn c s mt nghin cu thm nh
v phi c thm nh li theo nh k m bo rng cc quy trnh ny vn m bo cho kt qu
mong mun. Cn c bit lu n vic thm nh cc SOP trong pha ch, kim nghim v lm v sinh.
Thm nh l hnh ng nhm chng minh, bng cc phng tin thch hp, rng mi nguyn liu,
Cp < grade >
Hiu
sut lc
cui,%
S tiu phn ti a /
m
3
khng kh
S vsv
ti a /
1m
3

khng
kh
S ln thay i
khng kh / gi
WHO
US FED
STD
209E
ASEAN
0.5 5 > 5
A < LAF > 100 IA Trng 99.997 3.500 Khng < 1 Lung khng
kh nh hng
B 100 IB Trng 99.995 3.500 Khng 5 Min. 20
C 10.000 II Trng 99.95 350.000 2.000 100 Min. 20
D 100.000 III Xm 95.0 3.500.000 20.000 500 Min. 20
IV en 85.0 > > > 10 20
qu trnh, quy trnh, h thng, thit b c s dng trong sn xut hay kim tra, cho ra mt cch n
nh nhng kt qu nh mong mun. Thm nh quy trnh sn xut, cc quy trnh sn xut trng yu
phi c thm nh c trc v sau khi thc hin.
2.5. Khiu ni
2.5.1. Nguyn tc
Tt c cc khiu ni v cc thng tin khc lin quan n sn phm c kh nng b sai hng u phi
c xem xt theo cc quy trnh bng vn bn v cc bin php khc phc cn c thc hin.
2.5.2. Thc hnh
C 10 ni dung c th (xem c th ti liu tham kho) nh:
Phn cng ngi chu trch nhim x l cc khiu ni v quyt nh bin php khc phc.
C SOP m t bin php tin hnh, k c khi cn phai thu hi. Cn c bit ch n nhng khiu
ni v gi mo. Phi ghi thnh h s y chi tit bt k khiu ni no lin quan n sai hng sn
phm. Nhng khiu ni ny cn c iu tra thu o.
Tt c cc quyt nh v bin php x l v khiu ni u phi ghi vo h s.
H s v khiu ni cn c r sot thng xuyn tm ra nhng du hiu c bit hoc ti din
v c chng l thu hi nhng sn phm ang lu hnh.
Cn thng bo cho c quan c thm quyn,
2.6. Thu hi sn phm
2.6.1. Nguyn tc
Cn phi c mt h thng thu hi nhanh chng, hiu qu cc sn phm bit hoc nghi ng b sai
hng.
2.6.2. Thc hnh
C 7 ni dung (xem c th Ti liu tham kho) nh:
C mt ngi chu trch nhim iu hnh v phi hp vic thu hi.
C SOP c kim tra, cp nht thng xuyn gip cho t chc thu hi.
Cn hng dn iu kin bo qun nhng sn phm thu hi khu vc tch bit.
m bo sn sng cung cp h s phn phi sn phm cho ngi chu trch nhim.
Ghi h s tin trnh thu hi v c bo co cui cng.
Kim tra nh gi thng xuyn hiu qu k hoch thu hi.
2.7. Sn xut v kim nghim theo hp ng
2.7.1. Nguyn tc
Vic sn xut kim nghim theo hp ng cn c xc nh r rng, c s nht tr v c kim sot
nhm trnh nhng hiu lm c th dn ti vic sn phm, cng vic, hoc hot ng kim tra cht lng
khng t cht lng mong mun. Cn c mt vn bn hp ng gia hai bn, trong xc lp r
nhim v ca mi bn.
2.7.2. Quy nh chung
Tt c k hoch sn xut, kim nghim theo hp ng, k c nhng thay i d kin (k hoch, k
thut) u phi theo ng giy php lu hnh sn phm.
Phi cho php bn hp ng c th kim tra c s bn nhn hp ng.
Vic ph duyt xut hng cui cng phi do ngi c y quyn thc hin.
2.7.3. Quy nh c th
Cc yu cu c t ra nh sau:
Bn hp ng
+ Bn hp ng chu trch nhim nh gi nng lc bn nhn hp ng, kh nng thc hin, GMP,

+ Bn hp ng phi cung cp cho bn nhn hp ng tt c cc thng tin cn thit tin hnh cc
hot ng theo hp ng mt cch chnh xc theo ng giy php lu hnh v cc quy nh khc.
+ Bn hp ng phi m bo tt c sn phm v nguyn vt liu pha ch do bn nhn hp ng
giao u t tiu chun, v sn phm phi do ngi c y quyn k lnh xut.
Bn nhn hp ng
+ Bn nhn hp ng phi c nh xng, my mc, thit b, kin thc v kinh nghim cng nh
nhn vin nng lc thc hin tho ng cng vic do bn hp ng t ra. Ch c nhng c s c
giy php sn xut mi c thc hin sn xut, kim nghim theo hp ng.
+ Bn nhn hp ng khng c chuyn cho i tc th ba cng vic k theo hp ng khi
cha c bn hp ng thm nh v chp nhn.
+ Bn nhn hp ng phi trnh nhng vic lm bt li, nh hng n cht lng sn phm
v/hoc kim nghim cho bn hp ng.
2.8. T thanh tra v thanh tra cht lng
2.8.1. T thanh tra
V nguyn tc:
+ Mc ch ca t thanh tra l nh gi vic thc hnh cc nguyn tc GMP trong mi lnh vc
sn xut v kim tra cht lng. Chng trnh t thanh tra c thit lp pht hin ra nhng khim
khuyt trong thc hin GMP v khuyn ngh cc bin php khc phc cn thit.
+ T thanh tra cn tin hnh thng xuyn, ngoi ra c th tin hnh trong cc tnh hung c bit
(thu hi sn phm, sn phm b loi b, hoc nhn c thng bo v k hoch thanh tra ca c quan Y
t).
+ Ban t thanh tra gm nhng nhn vin c th nh gi khch quan vic thc hin GMP, tt c cc
khuyn ngh bin php khc phc phi c thc thi.
+ T thanh tra phi c ghi vo h s, v c chng trnh theo di hiu qu.
Thc hnh t thanh tra
Cc ni dung yu cu phi c (xem c th ti liu tham kho):
+ Danh mc t thanh tra: Phi c bn hng dn t thanh tra bao gm cc yu cu t thanh tra,
trong c th c cc cu hi v GMP. Danh mc t thanh tra ti thiu phi c (checklist) nh: nhn
vin, nh xng, k c khu vc dnh cho nhn vin; vic duy tu bo dng nh xng v my mc,
thit b; vic bo qun nguyn liu ban u v thnh phm, my mc thit b,
+ Ban t thanh tra, do lnh o ch nh mt Ban t thanh tra, tuyn ti ch, nhng chuyn gia
chuyn ngnh v am hiu GMP. Thnh vin c th trong hoc ngoi cng ty.
+ nh k t thanh tra, tn s ty thuc yu cu cng ty, ti thiu mi nm/1 ln.
+ Bo co t thanh tra, lp bn bo co sau khi kt thc t t thanh tra,
+ Bin php theo di, cn c mt chng trnh theo di c hiu qu.
2.8.2. Thanh tra v cht lng
+ Vic thanh tra cht lng bao gm ni dung kim tra v nh gi ton b hoc mt phn ca h
thng cht lng vi mc ch c th l hon thin h thng.
+ Vic thanh tra cht lng thng do cc chuyn gia bn ngoi v c lp hoc mt nhm do ban
lnh o cng ty ch nh.
+ Phm vi thanh tra cht lng c th m rng n cc nh phn phi v cc n v hp ng (xem
phn sn xut v kim nghim).
+ Thanh tra nh cung cp. B phn kim tra cht lng c trch nhim cng cc b phn lin quan
trong vic quyt nh ph duyt cc nh cung cp nguyn liu, Cc nh cung cp nguyn liu ny cn
c nh gi bng cc tiu chun quy nh trc khi duyt.
2.9. Nhn vin
Yu t con ngi l mt trong nm yu t c bn ca GMP
2.9.1. V nguyn tc
Vic thit lp v duy tr mt h thng m bo cht lng t yu cu sn xut cng nh kim tra
cht lng chnh xc ty thuc vo yu t con ngi. V vy, cn:
+ i ng nhn vin c trnh thc hin cc nhim v thuc phm vi trch nhim ca nh sn
xut. Trch nhim c nhn c ghi r trong bn m t cng vic.
+ Tt c nhn vin phi am hiu GMP.
2.9.2. Cc quy nh chung
+ nhn vin vi cc trnh chuyn mn, kinh nghim cn thit. Trch nhim mi ngi khng
nn qu nhiu. Tt c phi nm vng GMP.
+ C bn m t cng vic, ghi r trch nhim cho tng ngi, khng c phn cng cng vic
chng cho.
+ C bin php phng nhng ngi khng phn s ra vo khu vc sn xut.
2.9.3. V nhn vin ch cht
+ Nhn vin ch cht gm trng cc b phn (sn xut, kim nghim,) ngi c y quyn,
trch nhim khng th y thc.
+ Yu cu nhn vin ch cht phi c trnh khoa hc, kinh nghim p ng quy nh ca lut
php Quc gia. Trnh hc vn gm cc ngnh phi hp gia Ho hc, Vi sinh hc, Khoa hc v
Cng ngh dc, Dc l v c cht hc hoc ngnh khoa hc c lin quan khc.
+ V tr Trng b phn sn xut v Trng b phn kim nghim c mt s trch nhim chung
hoc cng thc hin lin quan n cht lng. Ty thuc tng quc gia, c th bao gm:
Ph duyt cc quy trnh bng vn bn v cc ti liu khc (c sa i).
Theo di v kim sot mi trng sn xut.
V sinh nh my.
Thm nh quy trnh sn xut v kim nh dng c phn tch.
o to, bao gm vic p dng v thc hnh nguyn tc m bo cht lng.
Ph duyt v theo di nh cung cp nguyn liu,
a) Trng b phn sn xut, c nhng trch nhim (6 iu c th xem Ti liu tham kho) nh:
m bo sn xut v bo qun sn phm theo ng h s,
Ph duyt cc hng dn sn xut k c kim tra trong sn xut.
m bo thm nh h s sn xut, v.v...
b) Trng b phn kim tra cht lng, c nhng trch nhim (9 iu c th xem ti liu tham
kho) nh:
Ph duyt hoc loi b cc nguyn liu, sn phm trung gian, bn thnh phm v thnh phm.
nh gi h s.
m bo thc hin tt c cc php th cn thit.
Ph duyt cc SOP ly mu, tiu chun cht lng, phng php phn tch v.v
2.10. o to
C 5 yu cu chnh:
1. Phi c k hoch v chng trnh o to bng vn bn cho tt c nhn vin.
2. Ngoi o to GMP, cn phi o to cho cc nhn vin mi nhng vn ph hp vi nhim v
c giao. o to lin tc, lu h s.
3. o to c bit i vi nhn vin lm vic nhng khu chuyn bit c nguy c tp nhim, c,
nguyn liu hot tnh cao.
4. Khng khch hng v nhn vin cha qua o to vo khu vc sn xut kim tra cht lng.
Nu khng trnh c th phi c thng bo trc, c bit v v sinh c nhn, trang phc v gim st
cht ch.
5. Chuyn vin c vn v nhn vin hp ng cng phi c o to v lu h s.
2.11. V sinh c nhn
8 yu cu c ra:
1. Tt c nhn vin phi c kim tra sc kho trc v trong khi lm vic.
2. Tt c nhn vin phi c o to v thc hnh v sinh c nhn. Tun th v sinh c nhn mc
cao. Cn c vn bn hng dn v quy nh thc hin ni quy ny (SOP).
3. Bt k ai c biu hin m au, vt thng h c th nh hng ti cht lng sn phm khng
c php x l nguyn liu u vo, bao b, sn phm,
4. Tt c nhn vin phi c hng dn v khuyn khch bo co vi ngi ph trch nhng du
hiu c cho l nh hng bt li n cht lng sn phm.
5. Nhn vin trnh dng tay tip xc trc tip nguyn liu, bao b, sn phm trung gian, bn thnh
phm v thnh phm.
6. Nhn vin phi mc trang phc lao ng (c m) ph hp cng vic.
7. Khng c ht thuc, n ung, thc phm trong khu vc sn xut, kim tra cht lng, bo
qun,
8. SOP v sinh c nhn, s dng trang phc bo h lao ng cho tt c mi ngi.
2.12. Nh xng
y l mt trong nm yu t c bn ca GMP.
2.12.1. Nguyn tc
Nh xng phi c b tr, thit k, xy dng, lp t v bo dng ph hp vi cc thao tc thc
hin trong khu vc sn xut.
2.12.2. Quy nh chung
1. Mt bng c b tr, thit k nhm gim thiu nhng ri ro sai st v d v sinh cng nh bo
dng trnh nhng bt li cho cht lng sn phm.
2. B tr trong mi trng c cc bin php bo v qu trnh sn xut gim thiu nguy c gy tp
nhim vi nguyn liu, sn phm.
3. Thit k v xy dng phi ph hp to iu kin m bo v sinh tt.
4. Thun tin cho cc hot ng bo dng, sa cha khng gy nguy hi n cht lng sn phm.
5. in, nh sng, nhit , m v vic thng gi phi ph hp, m bo khng nh hng bt li
ti dc phm trong qu trnh sn xut, bo qun, chnh xc ca my mc thit b.
6. Nh xng thit k v trang b m bo ngn nga cn trng v cc ng vt khc.
2.12.3. Quy nh c th mt s khu vc
a) Khu vc ph tr
Cc khu vc gii lao, v sinh phi b tr tch bit khi cc khu vc sn xut v kim nghim.
Phng thay v gi qun o, khu vc tm ra v v sinh phi thun tin v ph hp vi s lng
ngi s dng. Nh v sinh khng c thng trc tip vi khu vc sn xut v bo qun.
Xng bo tr nn tch khi khu vc sn xut (nu c iu kin).
Nh nui sc vt phi c cch ly tt khi cc khu vc khc.
b) Khu vc bo qun
khng gian v din tch bo qun c th t nhiu loi nguyn vt liu, sn phm khc nhau,
sn phm trung gian, bn thnh phm, sn phm bit tr, sn phm loi b, b tr v hay thu hi.
iu kin bo qun tt, kh ro, nhit , m,... C kim tra theo di.
Khu vc nhn v gi hng phi m bo khng b nh hng bi thi tit.
Khu vc bit tr phi ring bit, nh du ch dn, v.v
B tr khu vc ly mu nguyn liu ban u. Nu ly ngay khu vc bo qun th phi vn hnh
th no trnh nhim cho.
Nhng nguyn vt liu, sn phm loi b, thu hi phi bo qun khu ring.
C khu an ton bo qun nhng ho cht gy nghin, cc cht nguy him.
Bo qun an ton c bit cho cc vt liu bao b in sn,
c) Khu vc cn
Phi c khu vc cn ring cho cc nguyn liu ban u, thit k kim sot bi, v.v
d) Khu vc sn xut
B tr khp kn cho sn xut dc phm.
Sn xut sn phm khng phi dc phm th khng nn tin hnh trong cng mt nh xng.
Trong trng hp ngoi l, phi ht sc cn trng.
Nh xng phi c b tr hp thc, ni tip nhau theo trt t hp l tng ng vi trnh t hot
ng sn xut theo mc sch cn thit.
Khng gian rng cho sn xut lp t my mc thit b, nguyn liu theo trt t trnh ln ln.
Nhng ni nguyn vt liu, bao b, sn phm trung gian, bn thnh phm tip xc vi mi trng,
th b mt bn trong (tng, sn v trn) phi nhn v khng nt k.
Cc ng dn, mng n, cc im thng gi v cc dch v khc phi thit k lp t trnh nhng
hc cha bi, kh v sinh.
Cc ng thot nc ln, trnh chy ngc.
Khu vc v sinh phi c thng gi tt. nh sng, c bit, c th kim tra bng mt.
Khu vc ng gi phi thit k v b tr c bit trnh ln ln, nhim cho.
e) Khu vc kim tra cht lng
Khu vc kim tra cht lng phi tch bit khu vc v sinh. Nhng khu vc th nghim sc vt, vi
sinh vt, ng v phng x phi b tr bit lp nhau.
Phng kim nghim phi thit k ph hp cc hot ng d nh tin hnh, khng gian, trnh
nhim cho.
Vt liu xy dng phng kim nghim phi ph hp tnh cht cng vic, cc cht s dng trong
vic kim nghim.
B tr ring cho cc thit b phn tch trnh nh hng do in t, rung, m, cc yu t ngoi
cnh khc, hoc nu cn th b tr ring bit cc dng c phn tch.
2.13. My mc thit b
y l mt trong nm yu t c bn ca GMP, c th tm tt cc yu cu chnh:
1. Yu cu v thit k, cu trc, lp t, iu chnh v bo dng cho ph hp vi cc hot ng s
tin hnh, nhm gim thiu nhng sai st, nhim cho, tc ng bt li n cht lng sn phm.
2. Yu cu v v sinh, c SOP, lch trnh, phng tin, dng c lm v sinh,
3. My mc, thit b, dng c dng trong kim nghim phi ph hp vi quy trnh th nghim.
4. Cc b phn trong my mc, thit b tip xc sn phm, khng c gy bt li cho sn phm
trong qu trnh sn xut, khng a (thi, g) thm cht l.
2.14. Nguyn vt liu
y l mt trong nm yu t c bn ca GMP
2.14.1. V nguyn tc
Mc tiu chnh ca nh my dc phm l sn xut ra thnh phm dng cho bnh nhn bng cch
phi hp cc nguyn liu (bao gm nguyn liu ban u, bao b, kh, dung mi, cht ph gia, thuc th,
k c vt liu dng dn nhn,).
Cc vt liu lm v sinh, bi trn my mc thit b khng c tip xc sn phm.
Tt c nguyn liu u vo v thnh phm u phi c bit tr ngay sau khi nhn hoc pha ch
cho n khi chng c xut em s dng hoc phn phi.
Tt c cc nguyn liu v sn phm c bo qun trong iu kin ph hp do nh sn xut quy
nh, theo nguyn tc FIFO.
Nc dng cho sn xut dc phm phi l nc ng tiu chun.
a) Nguyn liu ban u
i vi nguyn liu ban u (starting materials), l mt khu quan trng, c cc yu cu:
1. Cn c ngi tham gia c kin thc ton din v sn phm v nh cung cp.
2. Ch nn mua ca nh cung cp c chp thun, hoc mua trc tip ca hng sn xut, thc
hin ng quy nh v nhn, ng gi, khiu ni,v.v
3. Phi kim tra tng chuyn hng: bao b, nim phong, phi khp vi n t hng v phiu giao
hng.
4. Tt c nguyn liu n u phi c kim tra, m bo l ng yu cu.
5. Tt c nhng tc nhn gy nh hng bt li ti cht lng nguyn liu (h hng,) u phi
c ghi chp v bo co b phn kim tra cht lng.
6. Nhiu l hng khc nhau trong mt t giao hng th phi ly mu, kim nghim mi l v xut
ring bit.
7. Nguyn liu ban u khu vc bo qun phi c dn nhn ph hp. Phi c nhng thng tin
ti thiu cn thit (xem thm ti liu tham kho).
Khi s dng h thng bo qun bng vi tnh ho, khng nht thit phi ghi r rng trn nhn tt c
cc thng tin nu trn.
8. Cn c quy trnh/bin php nhn dng nguyn liu bn trong mi thng.
9. Ch nguyn liu kim tra cht lng ph duyt xut v cn hn dng mi c s dng.
10. Ch ngi c y quyn l c php cn nguyn liu theo SOP nh sn.
11. Tt c nguyn liu sau khi cn, cn kim tra li khi lng/th tch v ghi li.
12. Nguyn liu xut cho mi l thnh phm phi c tp kt cng mt ni, c nhn r rng.
b) Nguyn liu bao b
1. Vic mua v qun l, kim tra cc nguyn liu bao b trc tip v in sn phi thc hin nh
nguyn liu ban u.
2. Cn c bit ch n bao b in sn, phi c bo qun trong iu kin an ton. Ch ngi c y
quyn l c php cp nguyn liu bao b cho s dng theo quy trnh nh sn.
3. Mi ln giao hng phi cho mt m s/k hiu nhn dng ring.
4. Bao b ng gi/in sn nu ht hn/khng dng c phi hy v phi c a vo h s.
5. Tt c sn phm v nguyn liu bao b khi giao cho b phn ng gi phi c kim tra s
lng, nhn dng theo hng dn ca quy trnh ng gi.
c) Sn phm trung gian v bn thnh phm
1. Sn phm trung gian v bn thnh phm phi c gi trong iu kin ph hp.
2. Khi mua v phi c giao nhn theo quy trnh ging nh nguyn liu ban u.
d) Thnh phm
1. Thnh phm phi c bit tr ti khi c lnh xut (quy nh ca nh sn xut).
2. Vic nh gi thnh phm v h s ti liu cn thit cho vic ra lnh xut mt sn phm bn
c m t phn thc hnh tt kim tra cht lng.
e) Nguyn vt liu b loi b v ti s dng
1. Nguyn vt liu b loi b cn c nh du r rng v bo qun khu vc hn ch ra vo.
2. Vic ti ch sn phm b loi b ch p dng trong trng hp ngoi l.
3. Vic s dng mt phn/ton b l trc (t cht lng) vo mt l cng sn phm, bt u t
mt cng on sn xut nht nh, phi c ph duyt.
4. B phn kim tra cht lng cn cn nhc thm cc php th vi thnh phm c ti ch.
f) Sn phm thu hi
Sn phm thu hi c phn bit v bo qun ring, cn c quyt nh x l sm.
g) Hng b tr li: phi hy b tr khi cht lng ca chng vn t yu cu,
h) Thuc th v mi trng nui cy
1. Tt c thuc th v mi trng nui cy phi ghi h s sau khi tip nhn/ pha ch.
2. Cc thuc th c pha ti phng kim nghim theo quy trnh duyt sn, nhn ghi nng , h s
hiu chun, hn dng, ngy cn chun li v iu kin bo qun. Phi c ch k ngi pha ch v ngy
thng.
3. Phi p dng cc php dng v m tnh xc nh tnh ph hp ca mi trng nui cy. C
chng th dng tnh phi ph hp vi nhy ca php th.
i) Cht chun i chiu
1. Nn dng chun chnh thc
2. Cht chun i chiu chnh thc ch dng vo mc ch c m t trong chuyn lun ph
hp.
3. Cht chun i chiu do nh sn xut t iu ch phi c kim nghim, xut xng, bo qun
ging nh Cht chun i chiu chnh thc, c ngi v c khu vc bo qun t tiu chun.
Cht chun th cp/cht chun phng th nghim c th c thit lp theo cc php th v kim
nghim ph hp m bo tiu chun ho.
Tt c Cht chun i chiu c bo qun v s dng ng quy nh ( m bo cht lng).
k) Nguyn vt liu ph thi
1. Cn c khu vc bo qun an ton ring ch x l.
2. Nguyn vt liu phn tch khng c php tch ly, cho vo thng cha tp kt bn ngoi
khu vc sn xut.
l) Nhng vn khc.
Thuc dit chut, cn trng, st trng lm v sinh khng c gy nhim my mc thit b,
nguyn vt liu, bao b, thnh phm,
2.15. H s ti liu
y l mt trong nm yu t c bn ca GMP, yu cu:
2.15.1 V nguyn tc
Qun l tt h thng h s ti liu l mt phn thit yu ca h thng m bo cht lng, v th
n c lin quan ti mi kha cnh ca GMP.
Mc tiu ca c ch qun l ny l xc nh cc tiu chun cho tt c nguyn vt liu v phng
php sn xut cng nh kim tra cht lng m bo l tt c nhn vin lin quan n sn xut u
hiu cng vic phi lm, khi no lm, m bo l nhng ngi c thm quyn u nhn c mi thng
tin cn thit khi quyt nh cho sn xut mt l thuc bn, m bo c cc bng chng, du hiu, h
s, cc thng tin cn thit cho php tin hnh iu tra (khi cn thit).
Vic thit lp v s dng h s ti liu ty thuc vo nh sn xut.
1. H s ti liu cn c thit lp, chun b, r sot v phn phi thn trng. Tun th nhng quy
nh trong giy php sn xut v lu hnh.
2. H s ti liu phi c duyt, ch k ca ngi c thm quyn, ghi ngy thng r rng. Khng
c thay i khi cha nhn c s chp thun ca ngi c thm quyn.
3. Phi c ni dung r rng: tiu , tnh cht, mc ch ca h s ti liu. Trnh by th t d kim
tra. Ti liu sao chp phi r rng, khng c sai st.
4. Thng xuyn r sot v cp nht. Khi mt ti liu c sa i, th phi c bin php ngn
nga s dng ti liu c.
5. Cc h s ti liu phi nhp s liu r rng, d c, khng c ty xo, khong trng nhp s
liu.
6. Bt k thay i no i vi mt ti liu cng phi k v ghi ngy thng. Nhng vn th hin sao
cho c th c c thng tin gc, l do
7. Lp h s ti liu /in h s ti liu khi tin hnh bt k hot ng no, sao cho c th truy
cp li c. H s ti liu v SOP c lin quan phi c lu tr t nht mt nm sau thnh phm lin
quan ht hn.
2.15.3. H s ti liu cn thit
2.15.3.1. Nhn
1. Nhn dng cho bao b, thng cha, my mc thit b /nh xng: r rng, theo mu thng nht
ca cng ty, mu sc,
2. Tt c thnh phm thuc phi dn nhn theo quy ch Quc gia, phi c cc thng tin ti thiu cn
thit nh:
Tn sn phm.
Danh mc hot cht (v tn chung quc t), hm lng mi hot cht.
S l do nh sn xut quy nh.
Ngy ht hn dng dng khng m ho.
Nhng iu kin bo qun c bit/nhng lu khi x l.
Hng dn s dng v lu cn thit.
Tn v a ch nh sn xut/ cng ty/ hoc ngi chu trch nhim.
3. i vi cht chun i chiu, nhn/ ti liu i km phi ghi r ngy sn xut, ngy ht hn dng,
ngy m bao b ln u v iu kin bo qun, nu cn.
2.15.3.2. Tiu chun cht lng nguyn liu ban u v nguyn liu bao b
1. Tiu chun cht lng nguyn liu ban u v nguyn liu bao b trc tip v bao b in sn cn
m t chi tit, ph hp, bao gm:
Tn nguyn liu (v tn chung quc t khng ng k c quyn INN, nu c) v s m ni b.
Tham chiu (reference) chuyn lun Dc in, nu c.
Quy trnh nh tnh v nh lng vi mc cht lng quy nh.
Ty thuc vo thc t cng ty, c th thm cc thng tin khc, (xem thm ti liu tham kho).
Nguyn liu bao b phi t tiu chun cht lng quy nh, c bit ch ti tng k vi sn phm.
2) H s ti liu m t SOP kim nghim phi nu r tn sut nh lng li mi nguyn liu, ty
thuc hn dng ca chng. SOP phi c thm nh trong iu kin nh xng, my mc thit b phn
tch hin c.
Cn c cc tiu chun cht lng ph hp c ph duyt v ghi ngy thng, k c cc php th
nh tnh, nh lng, tp cht v xc nh cht lng i vi nguyn liu, bao b v thnh phm;
nu c th, cn c c tiu chun cht lng sn phm trung gian, bn thnh phm, tiu chun cht lng
ca nc, dung mi v thuc th (acid v base). Mi tiu chun cht lng u c ph duyt v lu
tr b phn kim tra cht lng/m bo cht lng /trung tm h s ti liu.
Cc tiu chun cht lng cn c sa i b sung nh k p ng yu cu Dc in Quc
gia/ Dc in khc.
Cn c trang b y cc Dc in, cc tiu chun tham kho, ph i chiu.
2.15.3.3. Tiu chun cht lng sn phm trung gian v sn phm ch ng gi (bn thnh phm:
Cn c ban hnh, tng t tiu chun cht lng nguyn liu, thnh phm, nu ph hp.
2.15.3.4. Tiu chun thnh phm
Tn sn phm v m tham kho nu c. Tn mi hot cht (v tn chung INN)
Cng thc hoc tham kho cng thc.
M t dng bo ch v chi tit ng gi.
Hng dn cch ly mu v kim nghim hoc tham chiu quy trnh lin quan.
Quy trnh nh tnh v nh lng vi mc cht lng quy nh.
iu kin bo qun, cc lu nu c v hn dng.
2.15.3.5. Cng thc gc
Mi sn phm v c l sn xut cn c Cng thc gc c ph duyt chnh thc. Cng thc gc
cn c:
1. Tn sn phm, c m tham kho lin quan n tiu chun cht lng sn phm.
2. M t dng bo ch, hm lng mi sn phm v c l.
3. Danh mc cc nguyn liu c s dng (tn chung quc t INN, nu c), s lng.
4. Cng b sn lng thnh phm d kin, gii hn cho php v sn lng sn phm trung gian, nu
c.
5. Nu a im sn xut v my mc thit b s dng.
6. Phng php, hoc s tham kho ca phng php.
7. Hng dn cc bc chi tit trong qu trnh ch bin.
8. Hng dn cc k thut trong qu trnh sn xut v gii hn cho php.
9. Quy nh v bo qun sn phm, iu kin bo qun c bit, nu cn.
10. Nhng iu c bit cn lu .
2.15.3.6. Hng dn ng gi
Cc hng dn ng gi chnh thc cho sn phm, quy cch ng gi v dng ng gi phi c
ph duyt v ban hnh chnh thc. Thng gm:
1. Tn sn phm.
2. M t dng bo ch, hm lng v phng php s dng nu c.
3. Quy cch ng gi: s lng, khi lng/ th tch.
4. Nguyn liu bao b cho mt c l chun: s lng, c v chng loi, m/ s tham kho.
5. C v d/bn sao chp v mu bao b in sn c lin quan, trn ch ch ghi s l v ngy ht hn
dng.
6. Cn ghi cc lu c bit nh kim tra khu vc v my mc thit b ng gi.
7. M t thao tc ng gi, c thao tc ph tr v my mc thit b s dng.
8. M t cc thao tc kim tra trong qu trnh ng gi, c hng dn cch ly mu v gii hn cho
php.
2.15.3.7. H s pha ch l
1. Cn lu tr h s pha ch l cho mi mt l sn xut. H s thit lp da trn nhng phn lin
quan n cng thc gc.
2. Kim tra v ghi chp: my mc thit b, khu vc sn xut, h s ti liu, sn phm.
3. Trong qu trnh pha ch cn ghi nhng thng tin vo thi im thc hin mi thao tc, sau khi
hon thnh h s ghi ngy thng, ch k ngi chu trch nhim pha ch, (chi tit xem thm ti liu
tham kho).
2.15.3.8. H s ng gi l
1. Cn lu tr h s ng gi l cho mi l/ mt phn ca l pha ch. H s c thit lp theo
hp ng ng gi. Phng php chun b h s cn quy nh c th.
2. Trc khi thao tc ng gi, cn kim tra: my mc thit b, khu vc thc hin thao tc, c ghi
chp li vic kim tra ny.
3. Cn ghi li nhng thng tin (xem thm ti liu tham kho) nh:
Tn sn phm, s l, lng bn thnh phm c ng gi, s l v lng thnh phm d kin v
lng thnh phm thc t, s lng cn i.
Ngy gi thc hin thao tc ng gi.
Tn ngi chu trch nhim tin hnh thao tc.
Ch k tt ca nhn vin vn hnh cc cng on chnh.
Cc kim tra nh tnh v thao tc theo hng dn ng gi, c kt qu kim tra.
Cc thao tc thc hin, my mc thit b v dy chuyn s dng. v.v
2.15.3.9. Quy trnh thao tc chun (SOP) v h s s sch
1. Cc SOP v H s s sch v vic tip nhn mi chuyn hng nguyn liu, bao b, cn thit lp
v ban hnh. H s s sch, chng t v bin nhn bao gm 8 mc (xem thm ti liu tham kho).
2. Cc SOP cho vic dn nhn, bit tr v bo qun ni b i vi nguyn liu ban u, nguyn liu
bao b v nguyn liu khc, nu cn cng phi thit lp c th.
3. Cn ban hnh SOP cho mi my mc thit b v dng c, gn my mc thit b.
4. SOP hng dn cch ly mu, ghi r ngi c quyn ly mu.
5. Hng dn ly mu cn phi c:
Phng php ly mu v k hoch ly mu, my mc thit b s dng.
Cc lu cn thit trnh nhim cho.
Lng mu cn ly.
Hng dn vic chia nh mu theo quy nh.
Loi bao b ng mu, ghi r dng cho mu v trng/thng.
Cc lu c bit, nht l mu v trng hay c hi.
6. SOP h thng nh s l (m) nhm nhn dng l sn phm trung gian, bn thnh phm hay thnh
phm.
7. SOP cho vic nh s l t cng on pha ch, ng gi.
8. SOP cho vic nh s l phi m bo khng trng lp cng mt s l.
9. Vic ra s l cn ghi li ngay (ghi trong nht k sn xut), ngy ra s l.
10. Cn c SOP cho vic kim nghim nguyn vt liu v sn phm mi cng on (phng php
v my mc thit b).
11. H s s sch phn tch t nht phi c cc s liu:
Tn nguyn vt liu/sn phm v dng bo ch, nu thch hp.
S l v nh sn xut/nh cung cp.
Tham chiu tiu chun cht lng v quy trnh kim nghim lin quan.
Kt qu kim nghim, c nhn xt v tnh ton v mc cht lng quy nh.
Ngy kim nghim v s tham kho ca thc nghim.
Ch k tt ca ngi thc hin php th.
Ch k ca ngi xc minh php th v tnh ton, nu thch hp.
Kt lun cho t hoc loi b, ngy, ch k ngi chu trch nhim.
12. Cn c SOP xut/loi b nguyn vt liu, sn phm, c bit xut thnh phm ra th trng.
13. Cn lu gi h s s sch vic phn phi mi l sn phm, to iu kin khi thu hi.
14. C s nht k my mc thit b chnh quan trng, thm nh, ngy, ngi thc hin.
15. Ghi chp vic s dng cc my mc thit b chnh v khu vc pha ch theo thi gian.
16. SOP v sinh, phn cng trch nhim, chi tit lch, phng php, thit b,
2.16. Thc hnh tt trong sn xut thuc
2.16.1. V nguyn tc: Cc thao tc trong sn xut phi tun theo cc SOP xc nh r rng ph hp,
c ph duyt ca ngi c trch nhim v sn xut v kinh doanh, vi mc tiu t c sn phm c
cht lng cn thit.
1. Tt c cc vic x l nguyn liu v sn phm nh v sinh, bit tr, ly mu, lu kho, dn nhn,
ch bin, ng gi v phn phi phi thc hin theo SOP, phi ghi chp vo h s lu.
2. Khng nn lm khc quy trnh nh. Nu phi lm khc trc th cng phi theo mt quy trnh
c duyt, c s tham gia ca phng kim tra cht lng.
3. Kim tra hiu sut bo m phn hao ht nm trong gii hn cho php.
4. Khng c tin hnh ch bin nhiu sn phm khc nhau trong cng mt lc hoc lin tip nhau
trong cng mt phng hay khu vc, tr khi xc nh khng c nguy c nhm ln/nhim cho.
5. Trong qu trnh sn xut, phi dn nhn hoc nh du tt c nhng nguyn liu, thng cha
nguyn liu, sn phm, ang ch bin, bao gm c hm lng v s l.
6. Cn phi hn ch ngi ra vo khu vc sn xut.
7. Khng c dng thit b sn xut dc phm vo mc ch sn xut khc.
8. Cc kim tra, kim sot trong qu trnh sn xut phi c thc hin trong khu vc sn xut.
2.16.3. Mt s yu cu phng nhim cho nhim khun
1. Cn thn trng khi sn xut bng cc nguyn liu kh trnh sinh bi v phn tn bi thuc
trong khu vc sn xut. Cn phi kim sot cht ch s lu chuyn khng kh. Nguy c nhim bn nh
bi, kh, vi sinh vt, t vt ca cc nguyn liu cn li trn thit b, my mc
2. C cc bin php ngn nga nhim cho, phi c kim tra nh k.
3. Khu vc sn xut, ni nhng sn phm d b nh hng (nhy cm) trong qu trnh sn xut phi
kim tra nh k (nh kim tra vi sinh v cc tiu phn).
2.16.4. Mt s yu cu i vi giai on ch bin
1. Khu vc sn xut v cc thit b u sch s v khng cn cc nguyn liu, sn phm, ca l
trc.
2. Thc hin kim tra kim sot thit b.
3. Kim tra cc thit b v thit b cung cp kh, nc trc khi sn xut. Khng c s dng cc
thit b h hng, khng n nh.
4. V sinh sau khi sn xut, cn phi nu r thi gian gii hn tnh t khi thit b c v sinh n
khi s dng.
5. Cc yu cu i vi cc dng c sn xut nh thng cha thuc, cc phng tin vn chuyn sn
phm, cc dng c o lng, thit b phn tch, cng c ra.
2.16.5. Vi cng on ng gi sn phm, cc yu cu nghim ngt cng c ra trnh nhm
ln, nhim bn
1. Cn thn trng trnh nhm ln, nhim bn sn phm trong ng gi. Cc sn phm khc nhau
khng c ng gi cc khu vc gn nhau.
2. Khu vc ng gi, dy chuyn ng gi, my in nhn phi sch s v khng c c cc nguyn
liu, sn phm, h s ca l trc. S kim tra phi c thc hin theo check list v kt qu kim tra
phi c lu vo h s.
3. Phi c nhn ghi r tn thuc, s l mi trm ca dy chuyn ng gi.
4. Cn phi dn nhn ngay sau khi ng ng v hn ng. Phi c SOP thch hp trnh ln ln
hoc dn nhn nhm.
5. Kim tra cht ch ni dung in thm trn nhn, trnh mt ni dung trn nhn, kim tra khi ct nhn
bng my, qu trnh ng gi (xem thm ti liu tham kho).
2.17. Kim tra cht lng
y l ngi bn ng hnh ca sn xut.
2.17.1. Nguyn tc chung
Khng nh rng kim tra cht lng l mt phn ca GMP lin quan ti vic ly mu, tiu chun
cht lng v kim nghim, v t chc, h s ti liu (lin quan n cht lng).
Yu cu mi mt c s sn xut phi c mt phng kim tra cht lng. B phn kim tra cht
lng phi c lp. ngun lc, iu kin,... thc thi nhim v c giao.
2.17.2. Nhng yu cu c bn/ti thiu trong kim tra cht lng
Cn c vt cht v trang thit b, nhn vin, SOP ly mu v kim nghim nguyn liu ban
u, bao b, sn phm trung gian, theo ng GMP.
Vic ly mu phi theo ng phng php v do nhn vin b phn kim tra cht lng tin hnh.
Phng php kim nghim phi c thm nh.
Phi lp h s chng minh cc SOP ly mu, thao tc, kim nghim c thc hin v ghi
li bt k s sai lch no.
Thnh phm phi c thnh phn theo ng cng thc nh tnh, nh lng sn phm nh trong
giy php quy nh.
Phi ghi chp li cc kt qu thanh kim tra v kim nghim cc nguyn vt liu, sn phm trung
gian, bn thnh phm v thnh phm theo tiu chun cht lng nh.
Khng mt l sn phm no c em bn khi cha c chng nhn sn phm t yu cu theo quy
nh trong giy php ca ngi c thm quyn.
Mu nguyn liu ban u v sn phm cn c lu tr c s kim tra sn phm sau ny khi
cn thit.
2.17.3. Nhim v khc ca b phn kim tra cht lng
Xy dng, nh gi v thc hin cc SOP kim tra cht lng.
Thm nh, nh gi, duy tr v bo qun cht chun i chiu, m bo ng nhn trn bao b
nguyn liu, sn phm, theo di n nh ca sn phm v hot cht.
Tham gia vo vic iu tra khiu ni lin quan n cht lng sn phm.
Theo di mi trng.
Tt c cc hot ng phi c thc hin theo SOP v nu cn phi c ghi chp li (xem thm ti
liu tham kho).
2.17.4. Kim sot nguyn liu, sn phm trung gian, bn thnh phm v thnh phm
C cc yu cu v:
Cc th nghim u phi c thc hin theo quy trnh xc nh. Kt qu kim nghim phi
c kim tra bi ngi gim st.
Mu phi i din c cho l nguyn liu.
Thao tc ly mu phi khng c gy nhim cho v nh hng n cht lng sn phm. Trnh
nhm, ln. C nhn ghi trn bao b ng mu (ni dung c th xem thm ti liu tham kho).
Dng c ly mu phi sch s, c th tit trng nu cn.
2.17.5. Cc th nghim cn thit
a) i vi nguyn liu v bao b
Phi c kim tra ng chng loi, tinh khit, hm lng v cc thng s khc trc khi a
vo s dng.
Cc th nghim nh tnh phi c thc hin trn mi n v ng gi ca nguyn liu.
Giy chng nhn cht lng ca nh sn xut nguyn liu phi l bn gc hoc bn photo c
chng thc, c cc ni dung cn thit (xem thm ti liu tham kho).
Yu cu kim tra, kim sot l mt phn ca h s l.
b) Thnh phm
Mi l thnh phm phi c mt phiu kim nghim.
Sn phm khng t cc tiu chun phi c hon tr.
c) Kim tra h s l
H s sn xut v kim nghim phi c kim tra khi xut l.
Thi gian lu gi mu: t nht mt nm sau khi ht hn dng. Mu lu phi c gi trong bao b
v c bo qun trong iu kin ghi trn bao b. Cc nguyn liu khc cn c lu tr t nht hai
nm nu n nh cho php. Lng nguyn liu hoc sn phm lu phi cho t nht hai ln kim tra
ton din.
d) Nghin cu n nh
Phng kim nghim phi nh gi cht lng v n nh ca thnh phm, nguyn liu cng
nh bn thnh phm nu cn.
Phng kim nghim phi xc nh hn dng v tui th trn c s nghin cu n nh.
C mt chng trnh nghin cu n nh di hn tip sau .
n nh phi c xc nh trc khi a ra th trng.

TI LIU THAM KHO
1. Hong Minh Chu, Gio trnh Cng nghip Dc Bi ging lp D5, THYD, TP. HCM, 1997.
2. B Y t, Hng dn ASEAN GMP 1996 (Bn dch 1997).
3. LE HIR, Abrgs de Pharmacie galnique, R.F.Paris 2, 2000.
4. B Y t, Hng dn thc hnh tt sn xut thuc theo khuyn co ca T chc Y t Th gii
(WHO GMP), H Ni, 2004.

CU HI LNG GI * CHN CU NG:
1. Yu cu i hi phi c GMP l do
a) Nhu cu thuc ngy cng tng;
b) KHCN sn xut thuc pht trin p ng nhu cu v thuc;
c) Xu th hi nhp v Vit Nam gia nhp ASEAN;
d) C a, b, c kt hp ng.
2. Vit Nam trin khai p dng cc nguyn tc tiu chun GMP ca ASEAN t
a) 1984; b) 1987; c) 1990; d) 1996.
3. Mc tiu ca GMP
a) m bo mt cch chc chn dc phm c sn xut ra mt cch n nh;
b) Lun lun t cht lng nh nh (nh thuc ng k);
c) Sn xut ra thuc cht lng tt;
d) a, b kt hp ng.
4. GMP l
a) Ton b nhng khuyn ngh cn thc hin cho php m bo cht lng ca mt thuc xc
nh trong iu kin tt nht;
b) Nhng khuyn ngh ny m t nhng mc tiu khc nhau phi t ti;
c) V t chc, con ngi, c s;
d) a, b, c lin kt ng.
5. GMP gip cho nh sn xut
a) Sn xut ra nhng thuc c cht lng n nh nh thuc nguyn mu c cp giy php
sn xut;
b) Nhng thuc c cc thuc tnh: Tinh khit (P), ng (I), hiu nghim (E) v an ton (S);
c) m bo cht lng, hiu qu v an ton;
d) a v b lin kt ng.
6. Nm yu t c bn ca GMP
a) Con ngi, nguyn ph liu, mi trng (c s sn xut), quy trnh (phng php), trang thit
b;
b) Con ngi, my mc, nguyn liu, v sinh, an ton;
c) Nguyn liu, c s sn xut, ti liu, v sinh, an ton;
d) C s vt cht, mi trng, ti liu, con ngi, a im.
7. Yu t con ngi trong mt c s sn xut thuc t GMP i hi
a) v s lng;
b) v tiu chun (cht lng);
c) C thc v thi quyt tm thc hin GMP;
d) a, b, c kt hp ng.
8. Yu t nguyn vt liu l mt yu t khng th thiu c, i hi
a) Hot cht tt, ng, s lng, cht lng, hiu qu;
b) Cc cht t dc tt, t tiu chun cht lng;
c) Nguyn liu bao b ng gi m bo tnh nng cn thit, ch loi tip xc vi thuc;
9. Mi trng, c s sn xut i vi mt x nghip dc phm t GMP i hi
a) a im thun tin, xa ngun nhim, khng gy nhim;
b) ng chc nng cho cc dy chuyn sn xut;
c) m bo cp v sinh;
10. Quy trnh v phng php sn xut (ti liu), h thng ti liu phi y
a) Cc ti liu k thut; b) H s l;
c) Cc quy trnh k thut; d) b, c kt hp ng.
11. Vit Nam p dng WHO GMP t nhng nm... v c... iu khon
a) 2002 v c 15 iu khon; c) 2004 v c 17 iu khon;
b) 2003 v c 16 iu khon; d) 2005 v c 17 iu khon.
12. Thm nh l:
a) Mt phn c bn trong GMP v cn phi c thc hin theo ng cng nh;
b) Hnh ng nhm chng minh, bng cc phng tin thch hp, rng mi nguyn liu, qu
trnh, quy trnh, h thng, thit b c s dng trong sn xut hay kim tra, cho ra mt cch
n nh nhng kt qu nh mong mun;
c) a, b kt hp ng; d) a, b u sai.
13. Sn xut theo hp ng tun th WHO GMP quy nh chung
a) Tt c k hoch sn xut theo hp ng, k c nhng thay i d kin (k hoch, k thut)
u phi theo ng giy php lu hnh sn phm;
b) Phi cho php bn hp ng kim tra c s bn nhn hp ng;
c) Vic ph duyt xut hng cui cng phi do ngi c y quyn thc hin;
d) b, c kt hp ng.
14. Tiu chun cp v sinh ca WHO GMP
Cp < grade > Hiu sut lc cui,%

Bi 3 (tip)
THC HNH TT PHNG KIM NGHIM THUC
(GOOD LABORATORY PRACTICE GLP)

1. M U
1.1. Mc ch v phm vi p dng
1.1.1. Mc ch
Vic thc hnh tt cc nguyn tc kim nghim thuc nhm nng cao tnh hiu qu ca h thng cc
phng kim nghim thuc trn c hai mt qun l nghip v v qun l k thut, k c khu vc qun l
nh nc v doanh nghip, nhm m bo tnh khch quan, trung thc v chnh xc trong vic nh gi
cht lng thuc.
1.1.2. Phm vi p dng
Nguyn tc Thc hnh tt phng kim nghim thuc c p dng cho cc phng kim nghim ca
Nh nc v ca cc doanh nghip, k c cc doanh nghip c vn u t nc ngoi, cc phng kim
nghim t nhn hay phng kim nghim c lp.
1.2. Mt s thut ng s dng trong gio trnh
V d nh n v kim nghim, h thng cht lng, h thng phn tch, v,v (xem thm ti liu
WHO
US FED
STD 209E
(a) (b) (c) (d)
A < LAF > 100 99.997 99.995 99.997 99.995
B 100 99.995 99.95 99.95 99.95
C 10.000 99.95 95.0 95.50 95.0
D 100.000 95.0 90.5 85.0 85.0
MC TIU
1. Pht biu c mc ch v phm vi p dng nguyn tc Thc hnh tt phng kim nghim
thuc (GLP).
2. K ra v gii thch c nhng ni dung chnh (12 iu) ca GLP.
3. Vn dng vo vic thc hin ti c s sn xut.
tham kho).
2. NGUYN TC THC HNH TT PHNG KIM NGHIM THUC
Trn c s 5 yu t v cc nguyn tc c bn ca GxP, GLP c th ho vo ni dung 12 iu ph
hp vi yu cu ca phng kim nghim thuc.
2.1. V con ngi
Th hin iu khon 1: T chc, nhn s v o to.
2.1.1. V t chc, b tr sp xp cc phng, cc n v qun l nghip v, k thut
Mt phng kim nghim thuc thng c chia lm nhiu n v kim nghim hoc cc b phn
c chuyn mn ho da trn k thut kim nghim (v d: Ho l, Vt l, Vi sinh vt) hoc chia theo
cc i tng l sn phm c kim nghim (v d: khng sinh, vitamin, dc liu...). i khi phng
kim nghim cn c cc n v kim nghim chuyn bit phc v cc nhu cu nh th v trng,
th ch nhit t, o lng vt l c bit...
Chc nng nhim v ca mi n v kim nghim cn phi c xy dng v c ngi c thm
quyn ban hnh chnh thc.
Ngoi cc n v kim nghim (hay cn gi l cc phng chuyn mn), mi phng kim nghim cn
phi c b phn ng k mu v b phn lu tr h s tiu chun cht lng. B phn ng k mu c
nhim v nhn mu v cc ti liu km theo, phn pht mu n cc phng chuyn mn v tr li kt
qu kim nghim. B phn lu tr h s tiu chun cht lng phi m bo cung cp cc tiu chun
cht lng cp nht v cc ti liu lin quan cho cc n v kim nghim.
Ngoi ra, phng kim nghim cn c mt s n v hu cn phc v cho vic cung ng trang
thit b, vt t, ho cht, dng c v sc vt th nghim.
2.1.2. V nhn s
Phi c y nhn vin c o to thch hp, c chuyn mn v kinh nghim hon thnh
cng vic c giao, khng c lm thm nhng cng vic c mu thun vi cng tc kim nghim.
Yu cu trnh chuyn mn ca cn b, nhn vin k thut:
a) Trng phng kim nghim v trng cc b phn phi c trnh i hc hoc sau i hc, c
kinh nghim trong lnh vc phn tch kim nghim v lnh vc kim tra, qun l cht lng thuc.
b) Kim nghim vin phi c bng i hc hoc sau i hc thuc mt ngnh chuyn mn thch hp
(dc, ho phn tch, dc l, sinh vt, vi sinh vt...).
c) K thut vin trung hc phi tt nghip cc trng trung cp chuyn nghip thuc cc ngnh ph
hp hoc o to v cng tc kim nghim.
d) Cng nhn k thut trnh s hc c o to mt trng dy ngh hoc c hc tp, km
cp ti cc n v kim nghim t nht mt nm.
Yu cu v s lng bin ch ph thuc vo quy m v iu kin c th ca mi phng kim
nghim. Ni chung t l gia k thut vin (trnh trung cp) v kim nghim vin (trnh i hc)
nn l 1:3 i vi phng kim nghim ho l, 2:5 i vi phng kim nghim sinh hc hoc vi sinh. Tuy
nhin, t l ny c th thay i tuy theo nhim v c th ca mi phng kim nghim.
2.1.3. V o to
C k hoch o to ngn hn, di hn, c bn, nng cao tu theo cc i tng khc nhau, c s
chun b k v c s vt cht, gio trnh v chuyn gia.
2.2. V c s vt cht v mi trng c ra cc yu cu iu 3 ca GLP
2.2.1. V c s vt cht
Yu cu v thit k ph hp, m bo iu kin lm vic cho cn b, nhn vin.
Yu cu v b tr cc phng chuyn mn, phi to c s ring bit cho cc hot ng kim
nghim khc nhau. Trong mt phng chuyn mn, phi c cc khu vc ring m bo s c lp
ca cc h thng phn tch. Phng th nghim sinh hc/vi sinh vt hay cht phng x phi cch bit vi
cc phng th nghim khc. Ring i vi phng kim nghim vi sinh vt, h thng cp kh sch phi
m bo ng cc tiu chun k thut quy nh. Phng kim nghim dc l phi c khu chn nui sc
vt th nghim thit k ng cc yu cu k thut quy nh.
Nn c nhng phng ring bo qun thuc th, cht chun, phng lu mu, khu vc cha
dung mi ho cht chy n, c hi. Nhng khu vc ny phi c lp vi khu vc tin hnh cc phn
tch v phi c trang b chng mi mt cn trng, nhim, chy n... iu kin khng kh: m,
nhit thch hp.
2.2.2. V mi trng
V mi trng tin hnh cc th nghim phi trnh cc nh hng qu mc ca nhit , m, bi,
ting n, cc rung ng v nhiu in t.
Vic i li ca nhn vin cng c quy nh thch hp.
2.3. V my mc trang thit b
c ghi trong iu 4: Thit b phn tch v hiu chnh thit b phn tch.
Yu cu v trang b cc my mc, dng c thch hp cho vic ly mu, phn tch, hiu chnh v x
l d liu. Cc thit b phn tch phi ph hp vi phng php kim nghim v phi p ng c yu
cu kim tra cht lng ca n v.
Yu cu v thit k, cu to, iu chnh v bo tr cho ph hp vi cc thao tc c thc hin trn
thit b , nhm gim thiu ti a sai s, cho php vic lm v sinh cng nh bo tr c d dng.
i vi cc thit b phn tch t ng v phn mm km theo phi cho kt qu chnh xc nh yu
cu v phi p ng cc tiu chun k thut lin quan n th nghim. Cc thit b ny phi c hiu
chnh nh k m bo kt qu phn tch khng mc sai st.
Tn s hiu chnh: Nu thit b khng c quy nh ring th phi thc hin ng theo quy nh chung
mc B, phn VI: Ph lc. Vic hiu chnh thit b, phi c thc hin theo mt lnh c th v phi
c lu vo s l lch ca my. Tn s hiu chnh thay i ty loi thit b. V d:
+ My o pH c chnh t nht mt ln/ngy.
+ My o im nng chy: hiu chnh hng thng.
+ My quang ph hp thu t ngoi: hiu chnh hng thng song phi c kim tra hng tun v
tin cy ca bc sng.
+ My quang ph hng ngoi: hiu chnh hng qu.
+ Cn phn tch, my o ch s khc x v my quang ph hunh quang: hiu chnh 6 thng/ln.
Yu cu v s sch theo di s dng: Phi c bn hng dn s dng (SOP), s ghi chp gi l s l
lch my gm nhng thng tin cn thit (xem ti liu tham kho).
2.4. V nguyn vt liu
c c th ho iu 5: bao gm thuc th, cht i chiu v sc vt th nghim.
2.4.1. Thuc th (TT)
Yu cu i vi TT phi c cht lng ph hp kt qu c chc chn v c tin cy cao.
Thuc th phi c mua t cc nh sn xut hay cc nh phn phi c uy tn, tt nht l dng
ng gi nh, thch hp s dng trong phng th nghim.
i vi mt s TT c tnh cht c hi hoc d chy n phi c s dng v bo qun theo mt
quy ch c bit m bo an ton.
C SOP pha ch TT. Ngi pha ch phi c trnh thch hp. TT sau khi pha phi c dn
nhn y vi cc chi tit: tn TT, nng , yu t chun ho (h s hiu chnh K), hn dng, iu
kin bo qun, ngy pha ch v tn ca ngi pha ch.
Phi c s ghi TT pha ch, gm c cng thc pha, theo ti liu no v tn ngi pha ch TT
phi dng bao b sch v dn nhn vi cc chi tit nh nhn chai, l gc.
Phi nh k kim tra nng ca cc dung dch chun v dung dch ion mu. Khi kim tra
thuc th nu thy c hin tng vn c, kt ta hay bin mu th khng c s dng.
Nc ct v nc kh khong (nc trao i ion) phi c coi l TT. Chng cn c kim tra t
nht mt ln trong thng bo m cht lng nc t tiu chun Dc in.
Yu cu khi nhn TT phi kim tra m bo cc chai l cn nguyn nim phong. Nu cc kt
qu nh tnh, nh lng v th tinh khit t th c th c chp nhn s dng. Nu khng t,
phi hy b.
Yu cu i vi cc TT d tr nn c tp trung bo qun ti kho trung tm.
Yu cu v an ton khu vc kho: phi c t v tr c th ngn nga c ho hon v c
trang b cc phng tin phng chy cha chy thch hp.
2.4.2. Cht i chiu
Cc cht i chiu dng trong phng kim nghim gm c cht i chiu gc v cc cht i chiu
th cp c to ra trong phng kim nghim.
Quy nh v vic qun l cht i chiu: do mt ngi chu trch nhim chnh v phi m s theo
di.
S theo di cht i chiu phi ghi li cc thng tin sau: s th t cht i chiu, tn cht i chiu,
ngun cung cp, s l hay m nhn dng (nu c), cng dng chnh (v d: cht i chiu cho ph hng
ngoi, cht i chiu tp cht cho sc k lp mng, HPLC), quy cch ng gi v iu kin bo qun.
Ngoi ra, tt c cc thng tin v c tnh, thng s k thut ca cht i chiu cng c lu li trong
mt h s ring. i vi cc cht i chiu th cp c to ra ti phng kim nghim, h s phi lu
li cc phng php v kt qu phn tch nh gi cht i chiu, cng nh tn ngi thc hin cc
phn tch.
Yu cu v bo qun phi ng iu kin quy nh v phi c nh gi nh k theo quy trnh
nh gi cht i chiu ca WHO m bo khng b h hng. Kt qu kim tra phi c lu li
trong s theo di cht i chiu cng vi tn ngi kim tra.
i vi cc loi cht i chiu th cp phi c ng gi theo nguyn tc dng cho mt ln
kim nghim nhm loi tr yu t mi trng nh hng n s n nh ca sn phm.
2.4.3. Sc vt th nghim
Yu cu v tiu chun hin hnh nh thun chng, thc n, phng php chm sc Yu cu
chung tri phi m bo ng tiu chun hin hnh. nh gi cht lng theo SOP nh k.
2.5. V phng php v h s ti liu
c th hin cc iu 6, 7, 8 v 9.
2.5.1. Tiu chun cht lng v phng php phn tch (mc 6)
Cc tiu chun cht lng dng trong phng kim nghim thng da vo cc chuyn lun ca
Dc in Vit Nam hin hnh, Dc in cc nc c B Y t Vit Nam cng nhn v cc tiu
chun c s. B phn lu tr tiu chun c trch nhim cp nht v lu tr cc tiu chun cht lng
cn thit cho cng tc kim nghim, gm c:
a) Dc in Vit Nam v cc Dc in nc ngoi, k c ph lc, bn b sung v bn hiu nh.
b) Cc tiu chun cht lng khng c trong Dc in, i vi nhng thuc c kim nghim da
trn tiu chun ca nh sn xut. Cc phng php kim nghim khng c trong Dc in do phng
kim nghim nghin cu ban hnh.
V phng php phn tch c th c rt ra t cc tiu chun quc gia hay quc t, t cc n bn
khoa hc hay do chnh phng kim nghim nghin cu, ng dng.
Vic chn phng php phn tch ph thuc vo c th ca mi phng kim nghim (yu cu c
th c ghi trong ti liu tham kho).
2.5.2. Mu th (iu 7)
C cc quy nh v vic:
a) Ly mu
Phi c tin hnh mt cch khoa hc v ng k thut.
i tng ly mu l cc nguyn liu dng lm thuc, cc dng thnh phm bo ch v cc sn
phm c coi l thuc dng trong ngnh Y t.
Yu cu i vi trng hp t kim tra cht lng thuc ca cc c s sn xut, bo qun, kinh
doanh phn phi thuc, trng hp thanh tra, kim tra, gim st cht lng thuc trong sn xut v lu
thng phn phi. Vi cc trng hp c th, xem thm Ti liu tham kho.
Vic ly mu cng c tin hnh trong trng hp c nhng thng tin v thuc km cht lng,
khng an ton, t hiu lc, c s khiu ni ca ngi s dng v cc trng hp nghi ng c lu hnh
thuc gi. Vic ly mu do thanh tra vin, cn b ca c quan qun l, kim tra cht lng nh nc
trc tip thc hin c s chng kin ca cn b c s c ly mu.
Ni ly mu l ni sn xut, bo qun hay lu thng phn phi thuc. V tr ly mu phi sch s,
mi trng xung quanh khng c ly nhim bnh vo mu v tc ng lm thay i tnh cht ca mu
nh: nhit , m, nh sng... ng thi khng mu tc ng n mi trng, nht l trng hp
mu l cc sn phm bay hi c hi.
Ngi ly mu phi l ngi hiu bit nm vng chuyn mn, nm c cc vn bn php quy v
qun l cht lng thuc, cc th tc php l v cc thao tc k thut ly mu.
C quy trnh thao tc ly mu (SOP ly mu), phng thc ly mu v s lng mu (phn IV: Ph
lc Ti liu tham kho).
b) Nhn mu
Mu v cc h s km theo c gi n b phn ng k mu. B phn ng k mu phi kim tra
mu theo cc yu cu quy nh nh: Tnh trng nim phong ca mu, tnh trng bao b v nhn c ghi
y cc thng tin cn thit nh: tn sn phm, ni sn xut, c mu, nng /hm lng, s l, s
ng k, hn dng, iu kin bo qun. Nu l mu do c s gi n phi c phiu yu cu kim nghim
vi cc chi tit cn thit (xem ti liu tham kho).
B phn ng k mu phi m s theo di, ghi li tt c cc chi tit lin quan: s th t ca mu,
ngy nhn mu, ngy chuyn mu n cc phng chuyn mn.
Mu trc khi kim nghim, mu lu v phn cn li ca mu sau khi kim nghim phi c
bo qun ph hp. Khi chuyn mu cho phng chuyn mn phi km theo bn sao tt c cc h s, ti
liu cn thit.
Trng hp mu c gi qua ng bu in, c quan nhn mu phi kim tra nim phong v cc
th tc quy nh, sau thng bo cho ni gi mu.
c) Lu mu
Yu cu mu lu phi c cng ngun gc (ly t cng mt l hng, ly cng mt thi im), vi
mu th v c bo qun theo ng iu kin quy nh, mu lu s c phn tch li trong trng hp
c tranh chp v kt qu kim nghim.
Vi cc yu cu c th khc cng c quy nh (xem ti liu tham kho).
2.5.3. Th nghim v nh gi kt qu (iu 8)
a) Th nghim
Vic kim nghim mu phi c tin hnh cng sm cng tt k t khi hon tt vic ghi chp ban
u (s ng k, tn mu th nghim,).
Th nghim c tin hnh da trn cc quy trnh c sn trong cc chuyn lun ca Dc in hay
tiu chun c s. Phi tnh ton, tr liu trc kt qu th nghim.
Khi kt qu thu c r rng, tin cy, vi cc trng hp sau:
Khng cn lp li th nghim i vi:
+ Cc phn tch nh tnh da trn php so mu, phn ng kt ta, ph hng ngoi, ph t ngoi, sc
k lp mng.
+ Cc th nghim v tinh khit, gii hn tp cht da trn php so mu hoc so c, sc k
lp mng.
Lun lun phi lp li th nghim t nht hai ln v ly gi tr trung bnh i vi:
+ Cc php phn tch nh lng cho d bng phng php no (chun , cn khi lng, o
quang, quang ph t ngoi, sc k kh, sc k lng hiu nng cao HPLC)
+ Cc o lng nhm xc nh tnh cht vt l nh pH, nng sut quay cc, ch s khc x, im
nng chy
Khi kt qu thu c khng r rng hoc khi sai lch gia nhng ln lp li th nghim vt ra
ngoi gii hn cho php:
t nht phi lp li th nghim hai ln na v do mt kim nghim vin khc tin hnh.
Nu kt qu cho bi hai kim nghim vin khng trng khp i vi cng mt mu th phi tm
hiu nguyn nhn, c th do thao tc ca kim nghim vin cha thnh tho, thuc th hng, cht i
chiu hng hoc do thit b gy sai s, m cao Nu xem xt thy khng phi v cc l do trn th
kt qu trung bnh ca mi kim nghim vin c ghi ring vo phiu.
Mi d liu lin quan vic kim nghim mu u phi c ghi vo hoc km vi h s kim
nghim (s liu cn, kt qu, th, sc k , quang ph ...).
b) nh gi kt qu phn tch
Kim nghim vin phi i chiu kt qu thu c vi cc ch tiu trong tiu chun quy nh. C
cc trng hp sau:
Nu kt qu kim nghim ph hp vi cc yu cu ca ch tiu hay mc cht lng trong tiu
chun th ghi kt lun t. Ch khi tt c ch tiu u t mu mi c kt lun l t phm cht theo
tiu chun quy nh.
Nu c s khc bit gia kt qu thu c v mc ch tiu hay mc cht lng trong tiu chun
quy nh th mu s c lm li bi mt kim nghim vin khc hay bi trng n v.
Nu kt qu kim nghim ln th hai ph hp vi ln u th kt qu c ghi vo phiu v
chuyn n th trng n v quyt nh v ghi kt lun. Trng hp mu khng t hoc kt qu phn
tch khng lp li, th trng n v (hay Trng phng kim nghim ca doanh nghip) l ngi c
thm quyn a ra kt lun sau cng.
Trong trng hp phng kim nghim c nhiu n v cng tham gia kim mu, nn n v kim
nghim chnh nh gi kt qu mt cch tng th.
2.5.4. H s v ti liu (iu 9)
Gm c:
1. S tay kim nghim vin.
2. H s phn tch.
3. Phiu kim nghim, phiu phn tch.
(xem Ti liu tham kho)
H s kim nghim phi c lu li trong sut thi hn s dng ca thuc v theo cc quy nh
hin hnh v lu tr h s ti liu. Khi ht thi hn lu phi lm th tc hu theo ng quy nh.
Cc quy trnh thao tc chun SOP c ngi c thm quyn ph duyt. Cc quy trnh ny
hng dn nhn vin tin hnh cc thao tc chung nh:
Ly mu, nhn mu lu tr.
Kim tra mu.
Nhn, s dng v bo qun cht i chiu.
Vn hnh, bo tr, lm v sinh v hiu chnh thit b.
Pha ch, dn nhn v bo qun thuc th.
X l kt qu phn tch, bo co kt qu.
X l cht thi.
Cc h s v ti liu khc nh: S nhn mu, lu mu; Tiu chun cht lng; S theo di thuc
th; S theo di cht i chiu; H s hiu chun.
2.6. Cc tiu chun khc
Ngoi ra, GLP cn ch trng ti h thng cht lng c th hin iu 2, cp v tui th
iu 10, an ton iu 11 v t thanh tra iu 12.
2.6.1. V h thng cht lng
c t ra nhm m bo hot ng ca phng kim nghim tun theo cc nguyn tc Thc hnh
tt phng kim nghim thuc.
2.6.2. V tui th
i vi thuc mi.
i vi thuc generic.
Thuc ngoi nhp.
Tu theo tng loi m c phng php v xy dng quy trnh ph hp nh:
Phng php gi ho cp tc.
Phng php theo di bnh thng.
Phng php nghin cu trn sn phm c nhit i ho.
2.6.3. V an ton trong phng kim nghim
C cc quy nh chung.
Cc phng tin bo h lao ng nh knh bo h, khu trang, gng tay... phi tun theo ng cc
hng dn.
Quy nh v cc ho cht c hi.
V x l cht thi.
2.6.4. V t thanh tra
C chng trnh, k hoch, ni dung, hnh thc, tn sut, phng php nh gi,...
nh gi hiu qu ca h thng cht lng sau khi t thanh tra.

TI LIU THAM KHO
B Y t, Nguyn tc Thc hnh tt phng kim nghim thuc Ban hnh theo quyt nh s
1570/2000/QBYT ngy 22/05/2000 ca B trng B Y t.

CU HI LNG GI
Xem cng phn cu hi vi bi GSP.

Bi 3 (tip)
THC HNH TT BO QUN THUC
(GOOD STORAGE PRACTICES GSP)
MC TIU

1. M U
1.1. Mc ch v phm vi p dng
1.1.1. Mc ch
m bo cung cp thuc c cht lng n tay ngi s dng i hi phi thc hin tt tt c cc
giai on lin quan n sn xut, bo qun, tn tr, lu thng, phn phi thuc.
Thc hnh tt bo qun thuc l cc bin php c bit, ph hp cho vic bo qun v vn chuyn
nguyn liu, sn phm tt c cc giai on sn xut, bo qun, tn tr, vn chuyn v phn phi thuc
m bo cho thuc c cht lng nh khi n tay ngi tiu dng.
1.1.2. Phm vi p dng
Cc nguyn tc Thc hnh tt bo qun thuc c p dng cho cc nh sn xut, xut khu, nhp
khu, bun bn, tn tr thuc, khoa dc bnh vin, vin nghin cu v trung tm y t.
1.2. Mt s thut ng s dng trong gio trnh
V d nh: bo qun thuc, thuc, nguyn liu, hot cht, v.v... (xem ti liu tham kho)
2. THC HNH TT BO QUN THUC GSP
Vi 7 iu khon ra cho GSP trn c s cc yu t v cc nguyn tc c bn ca GxP, c th tm
tt nh sau:
2.1. V con ngi
c c th ho iu 1 Nhn s
2.1.1. Yu cu v s lng v trnh ty theo quy m ca n v, kho thuc phi c nhn vin, c
trnh ph hp vi cng vic c giao lm vic ti khu vc kho, c o c trung thc. Mi nhn
vin phi thng xuyn c o to v Thc hnh tt bo qun thuc, v k nng chuyn mn v phi
c quy nh r trch nhim, cng vic ca tng ngi bng vn bn.
2.1.2. Chc nng ca cc cn b ch cht ca kho l gim st, kim tra, cn phi p ng cc quy nh
ca Nh nc.
2.1.3. Yu cu v cc th kho i vi kho thuc thng, thuc c hi, v.v...
1. K ra c mc ch v phm vi p dng GSP.
2. Trnh by c ni dung chnh ca GSP (nhn s, nh kho, v sinh, cc qu trnh,...)
3. Vn dng theo hng dn thc hin.
2.2. C s vt cht
c c th ho iu 2 Nh kho
Yu cu v thit k, xy dng, trang b, sa cha v duy tu mt cch h thng sao cho c th bo v
thuc, nguyn liu trnh c cc nh hng bt li c th c, nh s thay i nhit v m, cht
thi v mi, cc ng vt su b, cn trng, m bo thuc c cht lng nh. Cc yu cu c th:
2.2.1. V a im
Kho phi c xy dng ni cao ro, an ton, c h thng cng thot nc, m bo thuc,
nguyn liu trnh c nh hng ca nc ngm, ma ln v l lt phi c a ch xc nh, thun
tin vic xut nhp vn chuyn, bo v.
2.2.2. V thit k, xy dng
a) Din tch phi rng, v khi cn thit, c th bo m vic bo qun cch ly tng loi thuc,
tng l hng theo yu cu.
b) Ty theo mc ch, quy m ca kho (kho ca nh sn xut, kho ca nh phn phi, kho ca khoa
dc bnh vin) cn phi c nhng khu vc xc nh, c xy dng, b tr hp l, trang b ph hp
cho cc khu nh: Khu vc tip nhn, bit tr v bo qun thuc, nguyn liu ch nhp kho. Khu vc ly
mu thuc, nguyn liu. Khu vc bo qun thuc. Khu ng gi ra l. Khu bit tr, v.v
c) Yu cu xy dng phng c ph hp (tng, trn nh,), thit k mt bng ph hp, v.v
2.3. V trang thit b
c c th ho iu 3 Trang thit b v iu 4 Cc iu kin bo qun trong kho
2.3.1. Nh kho phi p ng cc yu cu sau:
C cc phng tin, thit b ph hp nh: Qut thng gi, h thng iu ho khng kh, xe ch
hng, xe nng, nhit k, m k
C nh sng bo m cc hot ng c chnh xc v an ton.
C cc trang b, gi, k sp xp hng ho. Khng c thuc, nguyn liu trc tip trn
sn kho. Khong cch gia cc gi k, gia gi k vi nn kho phi rng m bo cho vic v sinh
kho, kim tra, i chiu, cp pht v xp, d hng ho.
C cc trang thit b, cc bn hng dn cn thit cho cng tc phng chng chy n, nh: h
thng bo chy t ng, thng ct, h thng nc v vi nc cha chy, cc bnh kh cha chy, h
thng phng chy cha chy (PCCC) t ng
C ni quy quy nh vic ra vo khu vc kho.
C cc quy nh v bin php chng s xm nhp, pht trin ca cn trng, su b, loi gm
nhm
2.3.2. Cc iu kin bo qun trong kho
V nguyn tc cc iu kin bo qun phi l iu kin ghi trn nhn thuc. Theo quy nh ca
WHO, iu kin bo qun bnh thng l bo qun trong iu kin kh, thong, v nhit t 15
25
o
C hoc ty thuc vo iu kin kh hu, nhit c th ln n 30
o
C. Phi trnh nh sng trc tip
gay gt, mi t bn ngoi vo v cc du hiu nhim khc.
Nu trn nhn khng ghi r iu kin bo qun, th bo qun iu kin bnh thng. Trng hp
ghi l bo qun ni mt, ng lnh th vn dng cc quy nh sau:
a) Nhit
Kho nhit phng: Nhit trong khong 15 25
o
C, trong tng khong thi gian nhit c
th ln n 30
o
C.

Kho mt: Nhit trong khong 8 15
o
C.

Kho lnh: Nhit khng vt qu 8
o
C.

T lnh: Nhit trong khong 2 8
o
C.

Kho ng lnh: Nhit khng vt qu 10
o
C.

b) m: iu kin bo qun kh c hiu l m tng i khng qu 70%.
i vi kho bo qun thuc, nguyn liu c yu cu bo qun c bit
Yu cu c cc bin php c bit c thc hin i vi vic bo qun cc cht c, cht nhy cm
vi nh sng, nhit , m, cht c hot tnh cao, v cht nguy him, nh: Cc cht lng, cht rn
chy n, cc kh nn, cc thuc gy nghin v cc cht tng t, cc thuc v ho cht c c tnh cao,
cc vt liu phng x, dc liu (c th xem thm ti liu tham kho).
2.4. Phng php v H s ti liu
c c th ho iu 4 Cc quy trnh bo qun (SOP) v iu 7 H s ti liu.
2.4.1. Cc quy trnh bo qun (SOP)
a) Yu cu chung
i vi thuc, nguyn liu cn c bo qun trong cc iu kin m bo c cht lng ca
chng. Vic lun chuyn theo nguyn tc nhp trc xut trc (FIFO:First In / First Out) hoc ht
hn trc xut trc (FEFO: First Expired/ First Out) cn phi c thc hin.
i vi thuc ch loi b cn phi c nhn r rng v c bit tr nhm ngn nga vic a vo
sn xut, lu thng, s dng.
Quy nh v chng trnh kim tra, nh gi nh k hoc t xut xc nh cht lng sn phm.
Phi c h thng s sch, cc SOP m bo cho cng tc bo qun, kim sot, theo di vic xut,
nhp v cht lng thuc.
b) V nhn v bao b
Bao b thch hp, khng nh hng xu n cht lng ca thuc, ng thi c kh nng bo v
thuc khi cc nh hng ca mi trng, trong mt s trng hp, khi c yu cu, bao b gip c vic
chng nhim khun.
Phi c nhn r rng trn tt c cc bao b ca thuc, d c, c cc ni dung, hnh thc p
ng cc quy nh ca php lut v nhn v nhn hiu hng ho ca thuc. Khng c dng tn thuc
vit tt, tn hoc m s khng c php. Tun th cc yu cu ca Dc in v cc quy nh php
lut lin quan n nhn v bao b.
Phi c cc h s ghi chp ring bit mi loi bao b, nhn hoc sn phm, trong ch ra cc iu
kin bo qun, cc bin php phng cn c ch v hn dng (nu c).
Phi c khu vc ring bo qun nhn thuc v cc bao b ng gi c in n. Phi c quy
nh c th cho vic nhp, xut cc loi nhn v bao b ny.
c) V tip nhn thuc
Vic tip nhn thuc phi c thc hin ti khu vc dnh ring cho vic tip nhn thuc, tch
khi khu vc bo qun. Khu vc ny phi c cc iu kin bo qun trnh cc nh hng xu trong
sut thi gian ch bc d, kim tra thuc.
Thuc trc khi nhp kho phi c kim tra, i chiu vi cc ti liu chng t lin quan v
chng loi, s lng, v cc thng tin khc ghi trn nhn.
Cc l hng phi c kim tra v ng nht, v nu cn thit c chia thnh cc l nh theo
s l ca nh cung cp.
Tt c cc bao b ng gi cn c kim tra cn thn v nhim bn v mc h hi. Tt c
cc thuc c bao b b h hi, mt du nim phong hoc b nghi ng c tp nhim th phi c bo
qun khu bit tr ch x l.
Cc thuc i hi iu kin bo qun c bit (cc thuc gy nghin, thuc c, cc thuc cn bo
qun nhit lnh...) phi nhanh chng kim tra, phn loi bo qun theo cc ch dn ghi trn nhn v
theo cc quy nh ca php lut.
Phi c lu cc h s ghi chp cho tng ln nhp hng, vi tng l hng.
Vic ly mu thuc kim tra cht lng phi c tin hnh ti khu vc dnh cho vic ly mu
v do ngi c trnh chuyn mn thc hin. Vic ly mu phi theo ng quy nh ti Quy ch ly
mu thuc xc nh cht lng.
Ch bit tr phi c thc hin hoc bng vic s dng khu bo qun ring bit, hoc bng h
thng x l d liu in t.
C cc bin php an ton phng trnh vic s dng hoc cp pht thuc, nguyn liu cha
kim sot, kim nghim hoc khng p ng yu cu quy nh.
Cc thuc, nguyn liu lu gi trong ch bit tr cho n khi c vn bn chp nhn hoc loi
b ca phng kim tra cht lng phi c cc bin php an ninh trong khi ch quyt nh hy, ti x l
hoc tr li nh cung cp. Cc thuc, nguyn liu nay phi c bo qun ring bit vi cc thuc,
nguyn liu khc.
d) V cp pht quay vng kho
Ch c cp pht cc thuc, nguyn liu t tiu chun cht lng, cn trong hn s dng.
Phi c v lu cc bn ghi chp (phiu theo di xut nhp thuc, phiu theo di cht lng
thuc...)
Vic cp pht cn phi tun theo cc nguyn tc quay vng kho (nhp trc xut trc hoc ht
hn trc xut trc), c bit l thuc, nguyn liu c hn dng. Ch khi mt loi thuc, nguyn
liu nhp sau c hn dng ngn hn thuc, nguyn liu cng loi c nhp trc th thuc, nguyn
liu c hn dng ngn hn phi c xut, cp pht trc.
Cc thng, bao thuc, nguyn liu c s dng mt phn cn phi c ng kn li mt cch
an ton trnh vic ri vi hoc tp nhim, nhim cho trong thi gian bo qun.
Cc thng, bao thuc nguyn liu b h hng, khng cn nguyn nim phong, mt nhn hoc nhn
b rch, khng r rng th khng c bn, cp pht, v phi thng bo ngay vi b phn kim tra cht
lng.
e) V bo qun thuc
Cc iu kin bo qun c yu cu nh: chng loi bao b, gii hn nhit , m, vic bo v
trnh nh sng... Cn c duy tr trong sut thi gian bo qun. Cn phi c s ch ti cc thuc
cha hot cht km bn vng i vi nhit , m, nh sng... (xem ti liu tham kho)
Bao b thuc phi c gi nguyn vn trong sut qu trnh bo qun.
Quy nh v ch bo qun i vi:
+ Cc thuc c, thuc gy nghin, thuc hng tm thn phi c bo qun theo ng cc quy
nh ti quy ch lin quan.
+ Cc thuc nhy cm vi nhit , cc thuc nhy cm vi nh sng, cc thuc d bay hi v cc
thuc nhy cm vi m, cc thuc c mi,v.v
+ Yu cu bo qun dc liu phi c kho kh, thng thong, v.v
Yu cu i vi cc cht d chy, n phi c bo qun ti kho ring, p ng cc quy nh ca
php lut.
C k hoch nh k tin hnh vic i chiu thuc trong kho so vi thuc hin cn v lng hng
tn theo phiu theo di xut nhp. Trong mi trng hp, vic i chiu phi tin hnh khi mi l hng
c s dng ht.
Thng xuyn kim tra s l v hn dng m bo nguyn tc nhp trc xut trc hoc ht
hn trc xut trc c tun th, v pht hin hng gn ht hoc ht hn dng.
nh k kim tra cht lng hng lu kho pht hin cc bin cht, h hng trong qu trnh bo
qun do iu kin nhit , m hoc cc yu t khc.
Thuc, nguyn liu khng t tiu chun cht lng, ht hn dng phi c bo qun khu vc
ring ch x l. Phi c cc bin php phng vic cp pht, s dng thuc, nguyn liu ht hn
dng, nguyn liu khng t tiu chun cht lng.
Phi c cc phng tin vn chuyn v bo qun thch hp nhm m bo cho thuc, nguyn liu
trnh v v h hng.
2.4.2. H s ti liu
c c th ho iu 7 ca GSP
a) Quy trnh thao tc (SOP) c ph duyt, k xc nhn v ghi ngy thng xt duyt bi ngi
c thm quyn. Cn phi c sn, treo ti cc ni d c xc nh phng php lm vic trong khu vc
nh kho. Phi m t chnh xc cc quy trnh v tip nhn v kim tra thuc nhp kho, bo qun, v sinh
v bo tr kho tng, thit b dng trong bo qun (bao gm c cc quy trnh kim tra, kim sot cn
trng, chut b...) quy nh v vic ghi chp cc iu kin bo qun, an ton thuc ti kho v trong qu
trnh vn chuyn, vic cp pht thuc, cc bn ghi chp, bao gm c cc bn ghi v n t hng ca
khch hng, thuc tr v, quy trnh thu hi v xc nh ng i ca thuc, v cc thng tin v thuc...
b) Yu cu c mt h thng s sch thch hp cho vic ghi chp, theo di vic xut nhp cc thuc,
bao gm tn thuc, s l, hn dng, s lng, cht lng thuc, nh cung cp, nh sn xut... p
ng cc quy nh ca php lut. Nu cc loi s sch c vi tnh ho th phi tun theo cc quy nh
ca php lut. Phi c cc quy nh, bin php phng nga c th trnh vic xm nhp, s dng, sa
cha mt cch bt hp php cc s liu c lu gi.
Phiu theo di xut nhp thuc.
Phiu theo di cht lng thuc.
Cc biu mu khc theo quy nh ca cc B, Ngnh c lin quan.
Phi c phiu theo di xut nhp thuc ring cho tng loi sn phm cng nh cho tng loi quy
cch sn phm.
i vi vic cp pht, tip nhn thuc c, thuc gy nghin, thuc hng tm thn phi tun theo
ng cc quy nh v h s ti liu ti cc quy ch lin quan.
2.5. Yu cu v v sinh
c ra, c th ho iu 3 ca ti liu GSP.
a) Khu vc bo qun phi sch, khng c bi rc tch t v khng c c cn trng, su b. Phi c
vn bn quy nh chng trnh v sinh, xc nh r tn s v phng php v sinh nh xng, kho. Ni
cch khc l phi c SOP v sinh.
b) Tt c th kho, cng nhn lm vic ti khu vc kho phi c kim tra sc khe nh k. Ngi
mc cc bnh v ng h hp, hoc c vt thng h u khng c lm vic trong khu vc bo qun
c trc tip x l thuc (nguyn liu, thnh phm) cn h.
Ni ra tay, phng v sinh phi c thng gi tt v b tr ph hp (cch ly vi khu vc tip nhn,
bo qun, x l thuc).
c) Cng nhn lm vic trong khu vc kho phi mc qun o bo h lao ng thch hp.
2.6. Cc iu khon khc
Cc vn khc c cp ti trong GSP nh: Thuc tr v ghi ti iu 5; Vic gi hng (vn
chuyn thuc bng cch gi hng) c ghi iu 6 (xem c th ti liu tham kho).

TI LIU THAM KHO
B Y t. Nguyn tc Thc hnh tt bo qun thuc, ban hnh theo quyt nh ca B trng B Y
t (29/06/2001).

CU HI LNG GI
1. Cht lng c xy dng vo trong sn phm c ngha l:
a) Cht lng sn phm (CLSP)ph thuc nguyn liu ban u;
b) CLSP ph thuc nguyn liu, nh xng, thit b v quy trnh sn xut;
c) CLSP ph thuc cht lng o to, hun luyn nhn vin v cht lng kim sot ca nhn
vin trong qu trnh sn xut;
d) Cht lng sn phm ph thuc c nhng yu t c ni n trong a, b, c.
2. m bo cht lng
a) L hot ng mang tnh d phng;
b) L cc hot ng p ng cu hi Ci g c lm m bo CLSP;
c) L hnh ng c lm trc khi tin hnh sn xut sn phm;
d) Khng cu no ng.
3. Kim sot cht lng
a) m bo cht lng thnh phm cui cng;
b) m bo cht lng nhng vic ang din ra;
c) L hnh ng tc nghip trc v trong qu trnh sn xut;
d) Khng cu no ng.
4. Hin nay u t pht trin GMP l yu cu khng bt buc i vi cc cng ty sn xut dc
phm nu cng ty mun tn ti v pht trin trong tng lai (/S).
5. Ni n cht lng thuc phi ni n tnh hiu qu, tnh an ton v kh nng chp nhn ca
ngi tiu dng (/S).
6. Nm yu t nh hng n cht lng sn phm trong sn xut: Mi trng sn xut, nguyn
liu, nh xng, thit b, quy trnh phng php sn xut, v yu t con ngi. (/S)
7. Ni dung kim sot cht lng trong qu trnh sn xut: Kim sot con ngi, kim sot phng
php v qu trnh, kim sot u vo, kim sot nh xng thit b, kim sot mi trng. (/S)
8. Hiu qu hot ng ca mt phng th nghim t chun GLP c nh gi bng s tho mn
nhu cu ca khch hng. (/S)
9. Phng th nghim t chun GLP phi qun l c hiu qu c v nghip v ln k thut. (/S)
10. Chc nng ca phng kim nghim thuc l nh gi phn loi thuc c t chun cht lng
ng k hay khng. (/S)
11. m bo thun tin trong giao tip cng vic, b tr cc phng chuyn mn ho l, vt l, vi
sinh, dc l cng cn k nhau cng tt. (/S)
12. Phng th nghim t chun GLP phi l phng th nghim c nhiu thit b phn tch hin i.
(/S)
13. Phi lp chng trnh v k hoch hiu chnh thit b nh k, thng xuyn cho cc thit b cn
kim nh, hiu chun. (/S)
14. Trong phng th nghim ch s dng cc ho cht thuc th c tinh khit P (Pure tinh khit)
v PD (Pure Analysis phn tch tinh khit). (/S)
15. Ch c Dc in Vit Nam hin hnh v Dc in cc nc c B Y t Vit Nam cng
nhn c s dng trong phng th nghim. (/S)
16. Thc hnh tt bo qun thuc nhm:
a) Hng ho trong kho khng b mt mt;
b) Hng ho khng b ht hn dng;
c) Hng ho c bo qun ng quy nh cht lng cn nguyn vn khi n tay ngi s
dng;
d) Tt c u ng.
17. Kho thuc c th l ni trung chuyn ca nhn vin v thit b t cc b phn khc.
a) Nu ca kho khng thng sang cc b phn ny;
b) Nu iu l cn thit trong trng hp khn cp;
c) Khng c v s gy nhm ln, ln xn v nhim cho;
d) Nu SOP c quy nh v iu ny.
18. Khi xut hng, cn tun th nguyn tc:
a) Nhp trc xut trc (FIFO);
b) Nhp sau xut trc (LIFO);
c) Ht hn trc xut trc (FEFO);
d) a v c ng;
e) b v c ng.
19. Cc loi thuc c, thuc hng tm thn c bo qun khu vc ring
a) V ch c dc s i hc mi c quyn cp pht cc loi thuc ny;
b) trnh mt mt v cc loi thuc ny thng c gi tr cao;
c) trnh nhm ln hoc nhim cho v cc loi thuc ny thng c c tnh cao;
d) Tt c u ng.
20. Vic x l, hu b hng ho h hng, km phm cht phi c tin hnh ti:
a) Khu vc giao nhn trong kho;
b) Khu vc cha hng ht hn ch hu;
c) Khu vc ring ngoi kho;
d) Khu vc cha bao b ngoi.
21. Vic theo di nhit , m trong kho:
a) Ch cn ghi li khi cn thit v nhit quanh nm khng chnh lch nhau;
b) Khng cn ghi li v nhit k, m k c kim nh ri;
c) Cn ghi li thng xuyn pht hin kp thi cc t bin v nhit , m c th nh
hng xu n cht lng hng ho;
d) Khng cn thit v tt c hng ho c bo qun nhit thng.
22. Nguyn liu d gy chy n c th c chung vi cc nguyn liu khc trong kho mt.
a) V kho ny c nhit thp c th ngn nga c chy n;
b) d qun l v cc nguyn liu ny thng t tin;
c) Phi kho ring, cch xa kho chnh v cc to nh khc;
d) Vi iu kin ch tm thi trong khi ch kim tra cht lng ly mu v cho php nhp
kho.
23. Vic giao nhn hng ho phi c tin hnh:
a) Trong khu vc bo qun;
b) Bn ngoi kho ni khng c mi che;
c) Ti mt khu vc ring trong kho dnh cho vic giao nhn;
d) Ti mt trong ba khu vc trn tu thuc ni no cn ch trng.

Bi 4
H THNG TIU CHUN CHT LNG ISO 9000

T nhiu nm nay, B h thng tiu chun cht lng c nhiu cng ty, doanh nghip trn th
gii p dng nhm hi nhp quc t theo xu th ton cu ho, l B tiu chun ISO 9000. Vy: ISO
l g? Do ai hay T chc no xy dng? H ISO 9000? ISO 9001 phin bn 2000 nhng iu khon
(yu cu) v phm vi p dng? Mi quan h ISO 9000 v GMP?
4.1. S lc vi nt v s ra i ca ISO v b ISO 9000
4.1.1. H tiu chun quc t ISO
ISO l ch vit tt ca International Standard Organization International Organization for
Standardization, l T chc tiu chun ho quc t, cn c gi l T chc tiu chun quc t, gi tt
MC TIU
1. K c s ra i ca ISO, ISO 9000.
2. K c cc h thng qun l cht lng trong h ISO 9000.
3. K c 20 iu khon chnh trong B ISO 9001.
4. Phn tch c mi lin quan ISO 9000 v GMP.
l ISO.
T chc ISO c thnh lp nm 1946, c s tham gia ca gn mt trm nc trn th gii, nhm
mc ch son tho mt s tiu chun chung cho sn xut, kinh doanh v truyn thng. Cho n nay ISO
hot ng trn nhiu lnh vc nh vn ho, khoa hc, cng ngh, kinh t, mi trng, v.v...
1985, T chc tiu chun quc t (ISO) a ra d tho b tiu chun quc t v h thng qun l
cht lng v c chp nhn vo nm 1987, b Tiu chun ISO 9000 c chnh thc s dng, tip
c hng lot nhng b sung.
1994, b Tiu chun ISO 9000 c sot xt ln u tin, nm 2000 xt li ln hai. T chc tiu
chun quc t d nh s sau mi 5 nm sot xt li mt ln.
ISO 9000 l mt b tiu chun hng dn cng tc qun l cht lng v xc nh cc yu t cht
lng chung cn thit cho vic m bo cht lng. ISO 9000 khng ph thuc vo bt c mt ngnh
ngh no. Mi cng ty, doanh nghip c th c th xc nh cho mnh mt phng thc ring vn
dng cc tiu chun ny nhm p ng nhng nhu cu ca mnh v ca khch hng.
ISO 9000 cp mt phm vi rng ri cc yu t c bn v c th ca h thng cht lng, khi
c iu kin ng k ISO 9000, cc cng ty, doanh nghip s c c mt h thng cht lng vi
y ti liu, cn c, c trin khai ton din v c theo di mt cch nht qun. Tuy nhin iu
khng c ngha sn phm ca cng ty hay doanh nghip ny s tt hn sn phm ca cc i th
khc.
Nhng tiu chun ISO 9000 khng phi l nhng tiu chun i vi sn phm. Chng khng h bao
hm nhng yu cu k thut. N c vai tr b sung nhng khng thay th cho nhng yu cu k thut c
th i vi sn phm.
Nhng Tiu chun ISO 9000 nu ra nhng iu cn t c ch khng hng dn phng php
thc hin. Vic la chn phng php thuc v cp qun l ca cng ty hay doanh nghip.
4.1.2. H Tiu chun quc t ISO 9000
C th tm tt cc h thng qun l cht lng (TC ISO 9000) trong h Tiu chun quc t ISO
9000 nh sau:
ISO 8402: Thut ng v cht lng.
ISO 9000: Qun l cht lng v cc tiu chun m bo cht lng.
Phn 1: Hng dn la chn v s dng (1994).
Phn 2: Hng dn chung v vic p dng ISO 9001 /2 /3 (1993).
Phn 3: Hng dn p dng ISO 9001 vo vic pht trin, cung ng v duy tr cc phn mm
(1991, sa lai 1993).
Phn 4: p dng vo vn m bo cht lng.
ISO 9001: Nhng h thng cht lng: M hnh m bo cht lng trong thit k trin khai, sn
xut, lp t v dch v (1994).
ISO 9002: Nhng h thng cht lng: M hnh m bo cht lng trong sn xut, lp t v dch
v (1994).
ISO 9003: Nhng h thng cht lng: M hnh m bo cht lng giai on kim tra v th
nghim cui cng (1994).
(Cc iu khon ca ba h thng ny c lit k bng 4.1).
ISO 9004: Nhng yu t c bn trong qun l cht lng v h thng cht lng.
C 4 phn:
1. Hng dn (1994)
2. Hng dn i vi cc dch v (1991, sa li 1993)
3. Hng dn i vi cc vt liu ch bin (1993)
4. Hng dn ci tin cht lng
ISO 10005: Qun l cht lng Hng dn lp k hoch (1995).
ISO 10007: Hng dn qun l chung.
ISO 10011: Hng dn kim nh h thng cht lng.
C 3 phn:
1. Hng dn kim nh (1990, sa li 1993)
2. Cc tiu chun v trnh chuyn mn i vi kim nh vin h thng cht lng (1991, sa li
1993)
3. Qun l cc chng trnh kim nh (1991, sa li 1993)
ISO 10012: Nhng yu cu m bo cht lng i vi thit b o lng.
Phn 1: Qun l cc thit b o lng (1992).
ISO 10013: Hng dn bin son ti liu v vn cht lng.
Ba m hnh m bo cht lng ISO 9001, ISO 9002 v ISO 9003 khng phi l ba cht lng khc
nhau. Chng ch khc nhau v phm vi tng ng vi nhng loi hnh t chc khc nhau. Chng hn,
ISO 9002 khng xem vic kim tra thit k nh mt yu t h thng cht lng.
4.1.3. Cc tiu chun hng dn v cc tiu chun hu ch khc
a) Cc tiu chun hng dn
ISO 90001 Cc tiu chun qun l cht lng v m bo cht lng Phn 1: Hng dn la
chn v s dng. Gii thiu H thng tiu chun ISO 9000 v gii thch nhng khi nim c bn v cht
lng.
ISO 90041 Qun l cht lng v cc yu t ca h thng cht lng Hng dn ci tin h
thng qun l cht lng: bao gm nhng hng dn i vi t chc v mc ch qun l cht lng,
khng lin quan n nhng yu cu hp ng bn ngoi.
Cn lu rng ISO 90041 ch bao gm nhng iu hng dn ch khng phi nhng yu cu c
th, nhng iu hng dn rt hu ch. N cng bao gm nhng vn khng c nu r trong ISO
9001 nh vn nh gi chi ph v vn lin tc ci tin cht lng. N cn c ch c bit t
khi cp n vn m bo an ton l vn khng c nu trong ISO 9001.
b) Cc tiu chun hu ch khc trong H thng ISO 9000
ISO 90002 Cc tiu chun qun l cht lng v bo m cht lng Phn 2: Hng dn chung
vic p dng ISO 9001, ISO 9002 v ISO 9003.
ISO 90003 Cc tiu chun qun l cht lng v m bo cht lng Phn 3: Hng dn p
dng ISO 9001 trong vic pht trin cung ng v duy tr cc phn mm.
ISO 90004 Cc tiu chun qun l cht lng v m bo cht lng Phn 4: Hng dn qun l
cc chng trnh lin quan n tin cy (i vi cc dch v in t, cung ng in, vin thng, thng
tin...).
ISO 90042 Qun l cht lng v cc yu cu ca h thng cht lng Phn 2: Hng dn i
vi cc dch v.
ISO 90043 Qun l cht lng v cc yu t ca h thng cht lng Phn 3: Hng dn i vi
cc vt phm c ch bin (Cc cht rn, lng hay kh c cung cp bng nhng ng ng, b cha,
can cha).
ISO 90044 Qun l cht lng v cc yu t ca h thng cht lng Phn 4: Hng dn ci tin
cht lng
ISO 90047 Qun l cht lng v cc yu t ca h thng cht lng Phn 7: Hng dn qun l
cu hnh.
ISO 10011 Hng dn kim nh cc h thng cht lng.
ISO 10012 Yu cu m bo cht lng i vi thit b o lng Phn 1: H thng kim tra cc
thit b o lng.
ISO 10013 Hng dn lp s cht lng.
Bng 4.1. Cc m hnh h thng cht lng ISO 9001, ISO 9002 v ISO 9003
Tn iu trong ISO 9001 ISO 9001 ISO 9002 ISO 9003
Trch nhim ca lnh o
H thng qun l cht lng
Xem xt hp ng ...
Kim sot thit k ... ...
Qua bng 4.1 cho thy ISO 9001 bao trm c hai m hnh cn li. ISO 9002 ch c mt trong s 20
iu khon l khng yu cu, ISO 9003 c 10 khon khng yu cu, cn li cc iu khon khc yu cu
thp hn ISO 9001. y cng l mt vn gy ra rc ri cho vic hng dn s dng v tr nn phc
tp cho la chn p dng khng ng c. Nn t nm 2000 thng nht s dng ch mt m hnh ISO
9001 thay th cho c 3 m hnh h thng cht lng c t nm 1994.
4.2. B tiu chun ISO 9000 nm 2000 (cn gi l phin bn 2000)
B tiu chun ny nhn mnh n nhu cu phi theo di s tho mn ca khch hng, theo st cc
nguyn tc qun l cht lng, gn gi hn vi ngi s dng bng ngn ng n gin, r rng. B tiu
chun mi m bo s nht qun gia tiu chun v hng dn.
Ngy 14/12/2000, ISO cng b b tiu chun quc t c sa i v h thng qun l cht
lng. B tiu chun ISO 9000 n hnh nm 2000 gm cc tiu chun di y:
ISO 9000: 2000, thay th ISO 8402: 1994, m t c s ca cc h thng qun l cht lng v quy
nh cc thut ng cho h thng qun l cht lng.
ISO 9001: 2000 thay th ISO 9001/2/3: 1994 (xem bng 4.1) quy nh cc yu cu i vi mt h
thng qun l cht lng khi mt tiu chun cn chng t nng lc ca mnh trong vic cung cp sn
phm p ng cc yu cu ca khch hng v cc yu cu ch nh c th p dng, v nhm nng cao s
tho mn ca khch hng.
ISO 9004: 2000, thay th ISO 9004 1: 1994, cung cp cc hng dn. Xem xt c tnh hiu lc
Kim sot ti liu v d liu ...
Mua sn phm ...
Kim sot sn phm do khch hng cung ng ...
Nhn bit v xc nh ngun gc sn phm
Kim sot qu trnh ...
Kim tra v th nghim
Kim sot thit b kim tra, o lng v th nghim ...
Trng thi kim tra v th nghim ...
Kim sot sn phm khng ph hp
Hnh ng khc phc v phng nga
Xp d, lu kho, bao gi, bo qun v giao hng ...
Kim sot h s cht lng
nh gi cht lng ni b
o to
Dch v ...
Cc k thut thng k
Ch thch: = Yu cu ton din
= Yu cu i hi thp hn so vi ISO 9001 v ISO 9002
... = Khng yu cu
v hiu qu ca h thng qun l cht lng. Mc ch l ci tin vic thc hin ca mt s t chc
v tho mn khch hng.
ISO 19011: 2001 thay th ISO 100111/2/3 cung cp hng dn v nh gi cc h qun l cht
lng v mi trng. Tiu chun ny s c ban hnh sau.
Cc tiu chun ca b ISO 9000 nm 2000 u c chuyn dch sang tiu chun Vit Nam tng
ng l TCVN ISO 9001: 2000.
4.2.1. c im ca b tiu chun mi
Nhng thay i ch yu ca tiu chun mi trong cp tiu chun h thng qun l cht lng ISO
9001 v ISO 9004 l:
Cu trc c nh hng theo qu trnh v ni dung sp xp logic hn.
Qu trnh ci tin lin tc c coi l mt bc quan trng nng cao h thng qun l cht
lng.
Nhn mnh hn n vai tr ca lnh o cp cao, bao gm c s cam kt i vi vic xy dng v
ci tin h thng qun l cht lng, xem xt cc yu cu ch nh v php lut, v lp cc mc tiu o
c ti cc b phn chc nng v cc cp thch hp.
Vic thc hin phng php cc ngoi l c php i vi tiu chun p ng c mt din
rng cc tiu chun v hot ng.
Tiu chun yu cu t chc phi theo di thng tin v s tho mn hay khng tho mn ca khch
hng. Thng tin ny c coi l mt php o v cht lng hot ng ca h thng.
Gim ng k s lng th tc i hi.
Thay i cc thut ng cho d hiu hn.
Tng thch cao vi h thng qun l mi trng (b ISO 14000).
p dng cht ch cc nguyn tc ca qun l cht lng.
Ch n cc nhu cu v quyn li ca cc bn quan tm.
4.2.2. Tm tt cc yu cu ca ISO 9001: 2000
Phn gii thiu cc tiu v yu cu ca tiu chun ISO 9001: 2000, s hiu cc mc chnh
c gi nguyn (nh trnh by bng 4.1).
ISO 9000 v GMP
Ging nhau: C nhng im ging nhau c bn v mc tiu, ch khc nhau cch h thng ho h s
v cch p dng.
Cng xy dng nn cc tiu chun (yu cu iu khon), cht lng v dng cc tiu chun ny
nh gi h thng cht lng ca mt doanh nghip.
Khc nhau:
ISO 9000 GMP
Vai tr ca h thng tiu chun ISO 9000 trn th trng quc t tr nn r rng. Nhiu khch
hng mong mun rng bn cung ng tin hnh ng k ISO 9001 i vi nhng cng ty/ x nghip c
sn phm thuc phm vi ch o ca Lin Hip chu u (EU) ng k ISO 9001 l mt yu cu php l
c th tham gia th trng chung chu u (EU). Vic ng k cng c th gip doanh nghip, cng ty
p ng c nhng quy nh trong nc.
Nm 2003, Vit Nam tham gia vo khu vc mu dch t do ASEAN gi tt l AFTA. Chng nhn
ISO 9000 tr thnh giy thng hnh cc doanh nghip hi nhp vo th trng khu vc v th gii.
Ngy nay, hu nh cc c s sn xut, nghin cu, kinh t x hi,... phn u thc hnh v ly
chng ch ISO 9001 phin bn nm 2000.

TI LIU THAM KHO
1. L Anh Tun. ISO 9000 Ti liu hng dn thc hin, Trung tm thng tin KHKT Ho cht H
Ni, 1999.
2. Bureau Veritas. Ti liu kho hun luyn chuyn gia nh gi cht lng ni b, TP. H Ch
Minh, 1999.
3. Tp ch Khoa hc k thut v kinh t, TP. H Ch Minh. S 20, 1999.
4. Ph c Tr v Phm Hng. ISO 9000 2000, NXB Khoa hc v K thut, 2002.

CU HI LNG GI * CHN CU TR LI NG
1.
a) ISO l ch vit tt ca International Standard Organization;
b) ISO l ch vit tt ca International Organization For Standardization;
c) L t chc tiu chun ho quc t;
c) a, b, c u ng.
2.
a) B ISO 9000 c chp nhn a vo p dng t nm 1985;
c cng nhn phm vi quc t.

Chng nhn do Bureau Veritas Quanlity
International cp.
Vit Nam: Tng cc Tiu chun o
lng cht lng cp.
Cng c khuyn khch thc hin, n
ph hp v h tr cho GMP.
Ty thuc vo khu vc, mc , phm vi
khc nhau: GMP ca cc nc, ca chu u,
ca ASEAN, ca WHO,...
Chng nhn GMP trong sn xut thuc do
B Y t Vit Nam cp. T 2005, Vit Nam
ly GMP WHO p dng.

Tiu chun u tin v bt buc.
b) B ISO 9000 c chp nhn a vo p dng t nm 1987;
c) B ISO 9000 c chp nhn a vo p dng t nm 1990;
d) B ISO 9000 c chp nhn a vo p dng t nm 1994.
3.
a) ISO 9000 l mt b tiu chun hng dn cng tc qun l cht lng v xc nh cc yu t cht
lng chung cn thit cho vic m bo cht lng;
b) ISO 9000 khng ph thuc vo bt c ngnh ngh, khu vc kinh t no;
c) ISO 9000 khng p t mt phng thc c th no cho mt cng ty, doanh nghip no;
4. ISO 9001 phin bn 2000 gm c:
a) 17 iu khon;
b) 19 iu khon;
c) 20 iu khon;
d) 21 iu khon;
5. ISO 9000 c p dng trn ton cu cho cc doanh nghip:
a) Sn xut thuc;
b) Sn xut thc phm;
c) Cc c s hnh chnh s nghip;
d) Tt c cc c s kinh t x hi.

Bi 5
AN TON LAO NG V V SINH CNG NGHIP

5.1. Mc tiu ca an ton lao ng v v sinh cng nghip
MC TIU
1. Nu c mc tiu ca an ton lao ng v v sinh cng nghip.
2. Trnh by c mng li t chc v an ton lao ng v v sinh cng nghip.
3. Trnh by v phn tch c bin php v sinh v tiu chun v sinh trong cng nghip dc
sn xut thuc.
4. Nu c mt s im cn lu cho cng tc an ton lao ng ti mt c s sn xut thuc c
th.
l c s sn xut cng nghip th an ton lao ng v v sinh cng nghip phi c ra ngang
tm quy m x nghip/ nh my/ cng ty. Nhm mc ch bo m s ton vn thn th ca ngi lao
ng, hn ch v bnh ngh nghip, gim s tiu hao sc khe, nng cao cht lng ngy cng gi
cng, gi vng v duy tr sc khe lu di v lm vic c nng sut lao ng cao.
5.2. V t chc thc hin
thc hin cng vic an ton lao ng v v sinh cng nghip, cn phi c t chc cht ch t trn
xung ti cc c s sn xut, t cp B n cc S tnh, thnh ph, v cui cng l cc x nghip, nh
my hay Cng ty.
x nghip, nh my hay cng ty, ngi chu trch nhim cao nht l gim c, tu theo mc
xp loi c s sn xut, m vic t chc thc hin sao cho ph hp. i i vi k hoch sn xut, dch
v phi c k hoch o to v hun luyn cn b cng nhn vin x nghip, nh my hay cng ty nhm
t c:
1. Am hiu nhng lut l, quy nh v an ton lao ng v v sinh cng nghip, ngha v v quyn
hn ca ngi lao ng, trch nhim trc nh my v c bn thn mnh.
2. Thc hnh nhng bin php v sinh, tiu chun v sinh v an ton lao ng ca nh my hay x
nghip ra.
3. Thc hin tt cng tc bo h lao ng...
5.3. K thut an ton v cc phng tin, bin php bo v ngi lao ng
5.3.1. K thut an ton
K thut an ton l h thng cc bin php k thut, phng tin v t chc thc hin nhm ngn
nga tc ng ca cc yu t nguy him trong sn xut i vi ngi lao ng.
Yu t nguy him trong sn xut l nhng yu t tiu cc pht sinh trong sn xut khi tc ng ln
ngi lao ng s gy tai nn lao ng. Cc yu t nguy him trong sn xut c th l:
+ Cc b phn truyn chuyn ng ca my mc thit b (nh cc bnh rng truyn, ai truyn,),
cc thit b chuyn ng (nh xe nng, my trc, t,).
+ Cc vt vng bn trong qu trnh sn xut (nh phi gia cng ct gt, mnh dng c vng ra gy
chn thng c hc, hoc v bnh cha ho cht vng bn gy bng v tc ng ho hc,), cc vt
ri, sp.
+ Cc yu t nhit , m cao hoc thp qu mc bnh thng.
Yu t v in, cc yu t chy n, cc cht c hi cng nghip, cc cht bi, bc x, ting n,
5.3.2. Cc phng tin v bin php bo v ngi lao ng
Thit b che chn cch ly vi ngi, d tho lp, khng nh hng n cht lng sn phm. Thit
b bo him. Cc tn hiu, bo hiu (c th l nh sng, m thanh, ng h ch bo, mu sn, hnh,).
Khong cch v gii hn an ton (khong cch an ton ca ng dy ti in, khong cch phng
x, khong cch an ton chy n,).
Phng tin bo v c nhn (bo v mt, u, chn tay, cc c quan nh h hp). Nhng bin php
t chc k thut (thit k my thit b c hnh dng, kt cu, mu sc ph hp v an ton, dng in
p an ton, t chc lao ng an ton trong sn xut, hun luyn an ton, xy dng quy trnh quy phm
tiu chun v k thut an ton).
a) i vi cc c s sn xut ni chung
Ngi s dng lao ng (gim c) phi thc hin theo lut lao ng, thc hin nhng quy nh v
an ton lao ng v v sinh lao ng. C th tm tt vo mt s vn nh sau:
Mi trng v c s lm vic
V tr nh xng: thun tin, cao ro, thng thong, bi theo quy nh, din tch, nh
sng, b tr ph hp vi yu cu sn xut,...
Trang thit b: Lp t thun tin cho thao tc, cho v sinh sa cha, phi che chn nhng b phn
truyn chuyn ng nh motor, rng rc,... nhm m bo an ton tuyt i cho ngi lao ng,...
i vi ngi lao ng
Ngi s dng lao ng c trch nhim trang b y phng tin bo h lao ng, bo m an
ton lao ng, v sinh v ci thin lao ng cho ngi lao ng.
Ngi lao ng phi tun th cc quy nh v an ton lao ng, v sinh v ni quy lao ng ca x
nghip, doanh nghip,...
Mi t chc v c nhn c lin quan n lao ng, sn xut phi tun theo php lut v an ton lao
ng, v sinh lao ng v v bo v mi trng. (B lut lao ng, 1994, tr. 60).
Phi c o to v hun luyn thun thc cc thao tc, vn hnh, s dng my mc,... nhm
m bo an ton tuyt i.
C chng trnh v k hoch o to hun luyn nh k.
Khm sc kho nh k,...
i vi lao ng n cn c nhng quy nh ring (B lut lao ng, NXB H Ni 1994, tr. 67).
b) Mt s im cn lu cho cng tc an ton lao ng v v sinh cng nghip
Nhng s in thoi cn nh:
115 Y t
114 Cu ho
113 Cng an
Ch
Tiu lnh cu ho.
C dng c v phng tin phng chy cha chy (cc bnh CO
2
, cc bnh xt khc,).

S dng thnh tho mi phng tin phng chy cha chy, mun vy cn phi c s hun luyn
nh k cho mi ngi trong x nghip, doanh nghip,...
Nhng ni d chy n cn phi c bin php phng nga hiu qu nht.
Nhng ni d xy ra nguy him phi c tn hiu r rng, d nhn bit c ban ngy v ban m. V
d bng bo hiu c ch sn hay du sn trn nn trng, c n vo ban m hoc bin bo
pht quang,...
Nhng phng tin, cc thuc s cp cu cn thit (t thuc cp cu).
Nhng cu dao in, nhng in,... cn phi c hp bao che,...
Nhng thit b chu p lc, thang my,... cn phi c s kim tra nh k v cho php s dng ca
c quan chc nng,...
5.4. V sinh cng nghip theo GMP trong c s sn xut thuc
Xut pht t c im ca ngnh Dc l sn xut ra mt loi hng ho c bit:
l nhng sn phm ng gi phn liu, i hi cht lng, an ton, hiu qu v kinh t.
Sch s v v sinh trong sn xut.
Quy nh cao v cht ch trong tng ch phm.
Sn xut theo tng l, m.
Sn phm c hn dng.
Mi dng bo ch ph hp theo ng s dng.
Tha hng v p dng nhng tin b khoa hc ca cc ngnh khc.
V th v sinh trong sn xut c ra v l mt trong cc vn quan tm hng u ca c s
sn xut thuc nhm mc tiu:
Loi b/ trnh nhim bi mi trng v ngi thao tc.
Loi b/trnh nhng sai phm, sai st, lm li, trong qu trnh sn xut.
Loi b/ trnh cc tc nhn nguy him cho ngi lao ng.
WHO GMP ghi khon mc 3, 11 v 12 yu cu v iu kin v sinh c nhn, nh xng, trang
thit b (xem c th ni dung WHO GMP Ti liu c thm).
a) Mt s im cn lu
Ngun nhim, c th phi k t nguyn liu, con ngi, thit b/dng c, bao b, nh xng,
khng kh v cc nguyn nhn khc (nh ln ln, sai st,).
Tc nhn nhim: Nhng tiu phn, vi sinh vt (V d: tng s khi lng vi sinh vt trn tri t
gp 25 ln tng s khi lng cc ng vt. ngi: trn da c ti 20.000 con vi sinh vt/cm
2
, trong
rut c 10
12
hay mt ngn t con/1gam phn), nhim cho (l vic nhim ca mt nguyn liu hay
mt sn phm bi mt mguyn liu hay mt sn phm khc).
Cc yu t chuyn ch s nhim: con ngi, khng kh mi trng (bn ngoi, bn trong v s
lc), lu cht (nh nc,) v lung di chuyn nguyn liu.
Hng ro ngn cn s nhim: cc cht gi (airlock), trang phc, chnh lch p sut, khu vc kn,
bao b kp, lc khng kh v v sinh.
Quy nh chung v:
iu kin v sinh
V sinh c nhn
V sinh nh xng
V sinh thit b, dng c sn xut
b) iu kin v sinh
cp ti cc vn :
S dng cht ty ra, cht ty u sao cho ph hp v bin php kim sot vi sinh vt.
Thu gom rc thi, cc vt liu loi b,
Vic dng cc cht ph gia khi cung cp hi nc (trnh cc cht gy ung th).
V vic lm v sinh cc khu vc, trnh nhim cho khi nhn vin qua li,
Cc tiu chun v sinh v SOP lm v sinh phi c thm nh trc v ti thm nh theo nh
k. Ch cc vn cn phi xc nh trc khi thm nh, v d cc iu kin lm v sinh my cn
phi xc nh (xem c th mc v sinh thit b).
c) V sinh c nhn
Cn quan tm ti cc yu cu v:
Sc khe ca nhn vin (khm sc khe, trc khi tuyn, trong thi gian lm vic theo nh k
hoc t xut khi c vn e v sc khe c lin quan n cht lng sn phm).
Thi quen v sinh (mt s iu cm k trong khu vc sn xut nh n ung, ct gi cc n
ung, thuc l, chi tc, ngoy mi, h mi,). thc gi gn v sinh nh trang phc, ra tay,
Phi c cc SOP v sinh c nhn v thc hnh v sinh v phi c o to, hun luyn.
d) V sinh nh xng phi m bo cc nguyn tc v nhng quy nh chung t thit k xy dng
n lp t thit b, b tr mt bng, v sinh d dng, thun tin cho thao tc trnh cc nguy c
nhim, nhim cho, cho mt nh xng sn xut thuc. Mi mt khu vc c cc yu cu v sinh ph
hp v phi c hng dn (cc SOP) c k hoch v sinh cho tng khu vc nh:
Khu vc ph nh cc phng v sinh v nh ngh, phng thay qun o, xng bo dng, nh nui
sc vt, phi tch ring.
Khu vc bo qun.
Khu vc cn, khu vc cp pht.
Khu vc sn xut (thuc bt, thuc nc, thuc v khun).
Khu vc kim tra cht lng,
e) V sinh thit b, trc ht phi c s lp t sao cho hn ch ti a cc nguy c sai st hoc tp
nhim. Mi mt thit b chuyn dng phi c SOP v sinh ph hp v cc iu kin v sinh cn phi
c xc nh:
V bn cht ca tc nhn gy nhim (gy nhim ngu nhin, nh kim loi, g, si, cc giong, cht
lng lm lnh, Gy nhim thng xuyn nh cn ca nguyn liu, ca sn phm ra, nc lm v
sinh, nc trng, du m,).
Cch thc nhim (c gi l nhim lin tip khi mt sn phm b nhim bi cc vt ca mt
sn phm khc trc trong cng mt thit b. c gi la nhim ng thi khi mt sn phm b
nhim bi cc vt ca mt sn phm khc c pha ch ng thi trong cc thit b khc v thng k
bn).
Tc nhn lm v sinh nh cc cht ty ra (cng t thnh phn, n gin, cng t nguy him, d
loi b, cng tt,).
Phng tin lm v sinh (th cng, t ng, phng php hn hp). Nguyn tc kh nhim (lm
v sinh trong t, sau khi thay i sn phm, sau bo tr,).
K thut lm v sinh,
V sinh dng c sn xut nh cc gng tay, cc bnh thp khng r, cc pallet vn chuyn v cc
dng c khc, v.v

TI LIU THAM KHO
1. Hong Minh Chu, Bi ging Sn xut thuc Cng nghip Dc. Trng i hc Y Dc. TP.
H Ch Minh, 1997.
2. Hng dn Thc hnh tt sn xut thuc theo khuyn co ca T chc Y t Th gii (Bn dch
ting Vit, Cc Qun l Dc, B Y t, H Ni, 2004).
3. B lut lao ng ca nc Cng ho X hi Ch ngha Vit Nam, Nh xut bn Chnh tr quc
gia, H Ni, 1994, tr. 60, 67.

CU HI LNG GI * CHN CU NG
1. i vi c s sn xut thuc, yu cu v sinh theo quy nh WHO GMP gm:
a) iu kin v sinh, v sinh c nhn, v sinh nh xng, v sinh my mc thit b (MMTB);
b) V sinh mi trng, MMTB, con ngi, nh xng, c nhn, tp th;
c) V sinh nh xng, MMTB, mi trng, c nhn, chng nhim;
d) a, b, c u ng.
2. i vi c s sn xut thuc, iu kin v sinh sch s, v sinh c nhn, v sinh nh xng v
v sinh thit b theo quy nh WHO GMP nhm mc ch:
a) Loi b/ trnh nhim bi mi trng v ngi thao tc;
b) Loi b/trnh nhng sai phm, sai st, lm li, trong qu trnh sn xut;
c) Loi b/ trnh cc tc nhn nguy him cho ngi lao ng;
3. An ton lao ng v v sinh cng nghip c ra nhm mc ch:
a) Bo m s ton vn thn th ca ngi lao ng, hn ch v bnh ngh nghip;
b) Gim s tiu hao sc khe, nng cao cht lng ngy cng, gi cng, gi vng v duy tr sc
khe lu di v lm vic c nng sut lao ng cao;
c) a, b kt hp ng;
d) C a v b u sai.
4. S in thoi cu ho quy nh nc ta l:
a) 114; b) 116; c) 111; d) 115;
5. S in thoi cp cu Y t nc ta l:
a) 114; b) 115; c) 110; d) 113;
6. Ngun nhim, c th do:
a) Nguyn liu, con ngi, thit b/dng c, bao b, nh xng;
b) Khng kh v cc nguyn nhn khc (nh ln ln, sai st,);
c) a, b kt hp ng;
d) C a v b u sai.
7. Hng ro ngn cn s nhim:
a) Cc cht gi (airlock), chnh lch p sut;
b) Trang phc, bao b kp, khu vc kn, lc khng kh v v sinh;
c) C 2 a v b u sai;
d) a, b kt hp ng.
8. Mi mt thit b chuyn dng phi c SOP v sinh ph hp v cc iu kin v sinh cn phi
c xc nh:
a) V bn cht ca tc nhn gy nhim v cch thc gy nhim;
b) Tc nhn lm v sinh, phng tin v k thut lm v sinh;
c) a, b kt hp ng;
d) C 2 a v b u sai.
9. Nguyn tc v sinh v thc hnh v sinh trong c s sn xut thuc, theo GMP:
a) Phi c thc hin nghim ngt trong tt c cc qu trnh sn xut v kim tra cht lng;
b) Phm vi thc hin l tt c nhn vin, nh xng, my mc, thit b, nguyn vt liu, bao b,
bt k th g c th l ngun ly nhim i vi sn phm;
c) C chng trnh tng th v nguyn tc v sinh v thc hnh v sinh;

PH LC
Trn c s nhn thc v cc GxP, theo nhng ni dung khuyn co ca WHO GMP, GLP, GSP ta
c th xy dng nhng cng vic c th cho mi c s doanh nghip nh mt vi v d di y:
1. Quy trnh thao tc chun
2. Bn m t cng vic
3. Thm nh
4. Nhn
V d:
Quy trnh (SOP) pha ch gc
Quy trnh (SOP) pha ch l/m
1. Tn doanh nghip 2. Quy trnh pha ch gc 5. Trang
6. Ngy ban hnh
3. B phn
4. n v
7. S
8. Ngy sot li
9. Thay th s ngy
10. Ngi son tho

Ngy:
11. Ngi kim tra

Ngy:
12. Ngi ph chun

Ngy:
Tn sn phm
S m
Dng bo ch
Ngy bt u
M s
C m
n v ng gi
Ngy kt thc
Cng thc: Vin M
Tiu chun k thut:
Nguyn liu
Thnh phm
Thit b v dng c
1. Tn doanh nghip 2. Quy trnh pha ch l/m 5. Trang
6. Ngy ban hnh
3. B phn
4. n v
7. S
8. Ngy sot li
9. Thay th s ngy
10. Son tho
Ngy:
11. Kim tra
Ngy:
12. Ph chun
Ngy:
Tn sn phm
S m
Dng bo ch
Ngy bt u
M s
C m
n v ng gi
Ngy kt thc
Cng thc: Vin M

Quy trnh thao tc chun
(STANDARD OPERATING PROCEDURE (SOP))
Vn hnh cn in t HR200
(Ch s dng chc nng cn)
1. Mc ch
m bo cc thao tc vn hnh c thc hin ng b t c s n nh v mt cht lng
sn phm, vn hnh an ton v hiu qu i vi thit b.
2. Phm vi p dng
Quy trnh ny c p dng trn Cn in t HR200, t ti tng 3 phng Thc tp thuc vin
B mn Cng Nghip Dc.
3. Quy trnh
Kim tra sch ca cn.
Cm ngun in cho cn.
Nhn nt ON/OFF ch vi giy cho n khi hin ra s: 0,0000
* Ch :
+ Nu cn khng hin ra s 0,0000 th bm nt REZERO ch hin ra s 0,0000.
+ Trong trng hp cn khi lng ln hn 50g nn iu chnh nhy ca cn nhm bo v cn
bng cch bm nt RANGE chuyn thnh 0,000 ri tin hnh cc bc k tip. Nu bm nt
RANGE mt ln na tr li 0,0000 nh ban u.
Tiu chun k thut:
Nguyn liu
Thnh phm
Thit b v dng c
HYD TP.HCM
KHOA DC
Quy trnh thao tc chun (SOP) T s: 1/2
Vn hnh cn in t HR200 S: SOP 312.00
Ngy: 7/7/1999
B mn:
Cng nghip Dc
Phng:
Thc tp thuc vin
C hiu lc t:
9/7/1999
Ngi son:
DS. H..
Ngy 7/7/1999
Ngi kim tra:
DS.Nguyn
Ngy 8/7/1999
Ngi duyt:
PGS. Hong
Ngy 9/7/1999
Ngy sot xt li:
9/7/2002
Thay th s:
Ngy:.
+ Trng lng ti a ca cn l 200g (k c b) do khng c cn qu 200g nhm trnh h
hng cn.
+ ng tc bm nt cn phi dt khot khng nn bm lu v bm lu cn s chuyn sang chc
nng khc khng ng mc ch s dng l cn khi lng v s lm hng cn.
+ Cc nt chc nng khc (dng vi mc ch khc) khng c bm s dng trnh lm sai lch kt
qu cn v gim chnh xc.
M lng cn v t b nh nhng ln a cn, ng lng cn, ch vi giy ri bm nt REZERO
ch hin ra s 0,0000.
M lng cn, cho nh nhng v t t vt cn cn ln a cn, ng lng cn. c kt qu cn trn
mn hnh (khi n nh).
Cn xong, ly b v vt cn ra. Bm nt ON/OFF cn tr v ch ngh.
Ngt ngun cung cp in cho cn.
V sinh cn theo SOP lm sch Cn HR200.
4. Trch nhim
Tt c cc cn b ging dy, k thut vin, sinh vin c phn cng vn hnh thit b k trn phi
c hun luyn v kim tra theo quy trnh thao tc chun ny trc khi tin hnh thao tc trn my.
Cn b hng dn thc tp chu trch nhim hun luyn, kim tra, gim st vic thc hin ca sinh vin.

Vn hnh cn xc nh m bng hng ngoi
SHIMADZU LIBROR EB 340 MOC
1. Mc ch
2. Phm vi p dng

HYD TP.HCM
KHOA DC
Vn hnh cn xc nh m bng hng ngoi
SHIMADZU LIBROR EB 340 MOC
S: SOP 311.00
Ngy: 3/7/1999
B mn:
Cng nghip Dc
Phng:
Thc tp thuc vin
C hiu lc t:
6/7/1999
Ngi son:
DS. H..
Ngy 3/7/1999
Ngi kim tra:
DS.Nguyn
Ngy 4/7/1999
Ngi duyt:
PGS. Hong
Ngy 6/7/1999
Ngy sot xt li:
6/7/2002
Thay th s:
Ngy:.
Quy trnh ny c p dng trn Cn xc nh m bng hng ngoi Shimadzu Libror EB 340
MOC t ti tng 3 phng Thc tp thuc vin B mn Cng nghip Dc.
3. Quy trnh
Kim tra sch ca cn.
Cm ngun in ca c cn v h thng un nng bng tia hng ngoi.
Bt nt < ON/OFF > ca b phn un nng (Heater unit):
n < POWER > chy sng.
n < 100 > nhp nhy.
Bm nt < ON > ca b phn cn:
Tt c n trn mn hnh (display) bt sng.
n nt < TARE > tren bn phm hoc nt < TARE > trn b phn cn mn hnh hin s: 0.000
(cho mu th 60g).
Nu xc nh lng mu th 60g < P < 330g th n nt < RANGE > mn hnh hin ra s: 0.00.
Vic s dng kt qu ny s gip bo v c nhy v chnh xc ca cn. Nu mun tr li nh ban
u vi 3 s l th bm < RANGE >.
iu chnh nhit sy bng nt < HEATER TEMP > ty theo yu cu ca mu th gm cc giai
on:
+ Gt kho v pha ngc chiu kim ng h m b chnh nhit .
+ Xoay nm vn (c 5 vng) chn nhit thch hp sy (0 500
0
C).

+ Gt kho v pha cng chiu kim ng h ng v c nh nhit ci t.
* Ch :
+ Nhit ci t l nhit ca ngun nhit pht ra cn nhit thc sy mu l nhit o
trc tip bng nhit k gn trn a cn cha ng mu, nhit ny ph thuc vo lng mu sy, th
tch, din tch b mt khi mu sy, hm m ca mu, Do thng phi qua th nghim vi ln mi
chn c nhit ci t thch hp.
+ S tng quan mt cch tng i gia nhit ci t v nhit thc sy ti a cn theo mi
quan h ca hm s m.
V d:
+ Nhit ci t l 300
o
C th nhit thc sy khong 100
o
C.

+ Nhit ci t l 400
o
o
C.

+ Nhit ci t l 500
o
o
C.

t thi gian sy bng cch nhn cc nt s trn bn phm (thi gian sy ti a l 99 pht).
V d: Nu cn sy trong 30 pht th n cc phm < 3 >, < 0 > v < TIMER >
t khoang d khi lng im dng sy kh (dry end point detection weight with), n v l
mg bng cch nhn cc nt s trn bn phm.
V d: Nu mun t 5mg th n cc phm < 5 > v < AUTO WEIGHT >.
t thi gian iu khin im dng sy kh (dry end point monitoring time) bng cch n cc nt
s trn bn phm ch c 4 cch la chn tng ng vi cc m s sau:
30 giy 05
2 pht 20
5 pht 50
Khng cn iu khin 99
V d: Nu cn t 2 pht th n cc phm <2>, <0> v <AUTO TIME>
t iu chnh t ng b phn HEATER CONTROL n cc nt < 1 >, < 0 > v < AUTO TIME >
nhm mc ch khi ht thi gian sy ci t my s pht ra ting ku bo hiu v t ng ngt.
t khong in t ng (automatic printing interval) theo di s bin thin ca hm m theo thi
gian nh my in in ra bng cch nhn cc nt < 8 >, < 0 > v < AUTO TIME >. iu ny ch cn thit
khi cn c ni vi my in EP50.
*Ch :
Do khng c my in nn mc t khong in t ng khng thc hin
n li nt < TARE >, ko mn chn ngun nhit bo v ngi s dng cn bng cch ko con
thoi v pha trc, sau nng nh nhng b phn Heater unit ln ri cho mu th ln a cn (nn tri
u mu th cho vic sy tin hnh d dng hn), gn nhit k theo di nhit thc sy ln a cn.
H nh nhng b phn Heater unit xung, m mn chn ngun nhit bng cch y con thoi v pha sau.
n nt < UNIT > trn bn phm mn hnh (display) hin ra 100% v thi gian sy ci t (v
d: 30 pht).
n nt < START > trn bn phm v theo di nhit trn nhit k, cn s t hot ng cho n
ht thi gian yu cu, mn hnh (display) s bo lin tc % trng lng mu cn li so vi trng lng
ban u v thi gian cn li so vi thi gian sy c ci t ban u. Khi ht thi gian sy theo yu
cu, my s t ng tt v s pht ra ting ku lin tc trong khong 15 giy.
n nt < UNIT > bit % m ca mu th.
n nt < ON > ca b phn cn bit trng lng sau khi sy ca mu th.
Tt cn:
+ Bt nt < ON/OFF > ca b phn Heater unit n v tr < OFF >.
+ Tt b phn cn.
+ Ngt ngun in cung cp cho cn.
V sinh cn theo SOP lm sch cn xc nh m bng hng ngoi SHIMADZU LIBROR EB
340 MOC s SOP..
4. Trch nhim
Tt c cc cn b ging, k thut vin, sinh vin c phn cng vn hnh thit b k trn phi c
hun luyn v kim tra theo quy trnh thao tc chun ny trc khi hun luyn thao tc trn my. Cn b
hng dn thc tp chu trch nhim hun luyn, kim tra, gim st vic thc hin ca sinh vin.

Vn hnh my o pH MELTROHM
1. Mc ch
2. Phm vi p dng
Quy trnh ny c p dng trn my o pH Meltrohm t ti lu 3 phng thc tp thuc vin B
mn Cng Nghip Dc.
3. Quy trnh
M l thng p trn in cc v ngm in cc vo nc ct khong 10 pht phc hi in cc.
Cm in, n nt < ON/OF > trn my pH ch hin ra cc thng s.
n nt < pH/mV/
o
C > ch hin ra cc thng s.

Nhng in cc vo dung dch m chun 1 (pH = 7.00).
n nt < pH CAL > mn hnh s hin ln: nhit , du ngn tay, CAL/U.
i n khi mn hnh xut hin th ly in cc ra khi dung dch m chun 1 (pH =
7.00), ra in cc bng nc ct v lau kh in cc bng khn giy mm ri nhng vo dung dch
m chun 2: (pH = 4.00) nu dng o trong mi trng acid; (pH = 9.00) nu dng o trong mi
trng base.
n nt < ENTER > i n khi mn hnh hin 2 ng xin v dc (slope) 90% slope
105% v pHas tng xng 6.40 pHas 8.00 th qu trnh chun my mi t yu cu nu khng th
phi pha li dung dch m chun. Ly in cc ra ra sch bng nc ct ri lau kh in cc bng
khn giy mm.
Nhng in cc vo dung dch cn o pH, mn hnh s hin ln pH ca dung dch cn o, nhit
v mt hnh tam gic nh hng ln hoc xung. c kt qu pH (kt qu n nh khi tam gic bin
mt).
o xong, ra sch in cc bng nc ct, lau kh ri tip tc o cc dung dch khc (nu c).
Khi khng o na, in cc phi c ra sch bng nc ct, lau kh ri nhng vo dung dch
KCl bo ho bo qun in cc, ng nt thng p trn in cc. Gn in cc vo v tr quy nh.
Rt in.
HYD TP.HCM
KHOA DC
Vn hnh my o pH MELTROHM S: SOP 312.00
Ngy: 7/7/1999
B mn:
Cng nghip Dc
Phng:
Thc tp thuc vin
C hiu lc t:
9/7/1999
Ngi son:
DS.
Nguyn..
Ngy 7/7/1999
Ngi kim tra:
DS.Nguyn
Ngy 8/7/1999
Ngi duyt:
PGS. Hong
Ngy 9/7/1999
Ngy sot xt li:
9/7/2002
Thay th s:
Ngy:.
4. Trch nhim
Tt c cc cn b ging, k thut vin, sinh vin c phn cng vn hnh thit b k trn phi c
hun luyn v kim tra theo quy trnh thao tc chun ny trc khi hun luyn thao tc trn my. Cn b
hng dn thc tp chu trch nhim hun luyn, kim tra, gim st vic thc hin ca sinh vin.
BN M T CNG VIC
Tn cng vic:
Bo co cho:
Gim st:
1. Kin thc:
K nng:
Kh nng:
2. Tm tt cng vic:
a)
b)

3. Nhim v v trch nhim:
a) Nhim v:
b) Trch nhim:
4. Quan h cng tc:
Vi
Vi

1.Tn c s/
doanh nghip
2. M t cng vic (ca tng ngi) 5. Trang:

Tn Chc danh:
Trng
6. S:
7. Ngy ban hnh:
1/1/2004
3. B phn 4. n v 8. Ngy c hiu lc:
1/1/2004
9. Ngy xem xt li:
1/1/2005
10. Ngi son:

Ngy:
11. Ngi kim tra:

Ngy:
12. Ngi duyt:

Ngy:
13. Thay th bn:
14. S:
15. Ngy:
5. K nhn ca ngi c giao:
6. Ni nhn (Lu tr, phn phi):
Ban Gim c
Phng (ban) T chc
Phng m bo cht lng
Phn xng sn xut

QUY TRNH THAO TC CHUN (SOP)
THM NH QUY TRNH V SINH THIT B
1. Mc ch
Hng dn cc nguyn tc tng qut vic thm nh cc quy trnh v sinh thit b trong sn xut.
Thm nh ny nhm chng minh rng mt quy trnh v sinh xc nh khi c p dng lm v sinh
b mt thit b trong nhng iu kin xc nh trc, s m bo mt cch n nh rng b mt
khng cn b nhim ( nhim cho hay cht ty ra cao hn gii hn c n nh trc).
2. Phm vi p dng
Tt c quy trnh v sinh cc thit b thit yu trong sn xut.
3. Trch nhim
Tt c nhn vin lin quan n vic thm nh cc quy trnh lm v sinh.
4. Cc iu kin cn thit trc khi thm nh
Cc thit b sn xut c nh gi t (nh gi lp t v vn hnh).
Nhn vin lm cng tc v sinh phi c o to v l thuyt v thc hnh lin quan n cng tc
v sinh.
Cc thit b dng lm v sinh phi c nh gi: my ht, my ra,
Cc tc nhn s dng trong khi lm v sinh phi c thm nh (v d cc cht st khun ).
Thm nh thit b lm v sinh hay mt tc nhn s dng trong khi lm v sinh l nhm chng minh

Tn doanh nghip
SOP thm nh quy trnh v sinh thit b T s
S
Ngy
Phn xng B phn Hiu lc t
Ngy sot xt li
Ngi son
Ngy
Ngi kim tra
Ngy
Ngi duyt
Ngy
Thay th s
Ngy
rng cc phng tin ny ph hp vi phng php lm v sinh, khng gy tn hi cho b mt phi
v sinh, khng pht sinh cng nh khng a vo cc cht gy nhim.
5. Ni dung
5.1. Cc mc sch khc nhau phi t c
Quy trnh ny phn loi 4 mc v sinh thay i ty theo mc tip xc vi sn phm.
Mc A: Tt c b mt ca khu vc v thit b. Khu vc ny c quy nh khng c cha
mt vt g khc ngoi dng c cn thit cho vic pha ch.
Mc B: Cc b mt bn ngoi ca cc thit b dng pha ch hay ra l.
Mc C: Cc b mt ca thit b c tip xc vi sn phm.
Mc D: Nc thi sau khi ra.
5.2. Vic la chn trng hp xu nht
Mi thit b c s dng sn xut nhiu sn phm cng lc, do nguyn tc la chn sn
phm thm nh l phi chn trng hp xu nht.
La chn hot cht thm nh da theo nguyn tc:
Chn sn phm no m liu iu tr ti thiu hng ngy (DMT) ca hot cht thp nht. i vi
nhng sn phm c cng hot cht ch khc nhau v hm lng chn sn phm c hm lng hot cht
cao nht.
Chn sn phm no m hot cht kh loi b ( tan thp) nht trong dung mi lm v sinh.
Sn phm c ngng pht hin nh lng rt thp (di hay bng microgram).
La chn sn phm lm sn phm k tip:
Chn sn phm no c liu ti a hng ngy (DMP) cao nht (g/ngy) lm sn phm k tip khi
thm nh.
i vi cc my mc thit b gn ging nhau v hnh th v cu to, s c lp thnh mt nhm,
khi vic thm nh quy trnh v sinh ch cn tien hnh trn my c kch thc nh.
Vic thm nh trng hp xu nht (thit b lin quan v sn phm c chn) s dn n phi
xem xt tt c sn phm no s c s dng vi thit b .
Mt khi sn xut mt sn phm mi, phi so snh sn phm ny vi sn phm xu nht. Nu sn
phm ny tr thnh sn phm xu nht, phi tin hnh thm nh li, ngc li s c coi nh l
thm nh.
La chn tc nhn ty ra: Tc nhn ty ra cng c xem l tc nhn gy nhim thit b mc d
n c s dng h tr v sinh thit b. Hu ht tc nhn ty ra thng gm vi thnh phn khc
nhau vi chc nng ring bit nh tc nhn hot ng b mt, tc nhn phn lp, v.v Ni chung hu
ht cc tc nhn ty ra dng trong phng php v sinh l nhng cht c nghin cu s dng
cho ngnh dc phm nn kh an ton, v vy cn p dng cc k thut phn tch ph hp thm nh.
Vic la chn thnh phn (C) trong cht ty ra phn tch da theo nguyn tc sau:
Tng i c hi hn so vi cc thnh phn khc (la chn u tin).
Kh tan hn so vi thnh phn khc: nh lng thnh phn ny c th c lng c ton b s
lng cn ca tc nhn ra.
5.3. Cc phng php ly mu
5.3.1. Ly mu trn b mt bng phng php pht
Vic ly mu b mt c th p dng cho tt c cc b mt v thit b, bt k l loi b mt g min l
nhng im ly mu u c th ly c.
Hiu sut ly mu v hiu sut chit phi c tnh ton trc.
5.3.2. Ly mu t dung dch trng
Phng php ny ch p dng cho cc thit b v c bit l cc thit b c cc im kh ly mu hay
cc thit b kh tho ri.
Vic la chn dung mi cn c vo:
tan ca cht gy nhim s thm nh;
Bn cht ca b mt c ly mu;
Thao tc d dng v an ton;
Chi ph.
S lng dung mi s dng phi c bit r.
5.3.2. Phng php Placebo
Nguyn tc ca phng php ny l sn xut ra mt l sn phm ch vi t dc tr. Phng php
ny thch hp i vi cc thit b lin hon, khi l t dc tr c i xuyn sut qua cc thit b ca
dy chuyn, t dc tr s b nhim lin tc tt c cc ngun nhim. iu ny cho php kim tra trc
tip cc tc nhn nhim tch ly ging nh thc hnh trn l sn xut tht.
i vi sn phm rn, cn lu n kh nng cho php sn xut ca t dc tr v kh nng phn
tn ca cht gy nhim s thm nh vo t dc tr.
i vi sn phm lng, nc l dung mi tr tt nht.
5.4. Cc phng php phn tch
Mt s phng php c th c p dng:
o in tr sut/ dn in, pH, lng acid/ base: c th p dng tm vt ca cc tc nhn lm
v sinh.
Phng php o quang ph UVVIS.
Sc k lng cao p (HPLC)
5.5. Tiu chun chp nhn
5.5.1. Tiu chun A
Theo tiu chun ny, tt c b mt phi sch khi quan st bng mt.
C th p dng cho cc hot cht, t dc v tc nhn v sinh.
Tiu chun chp nhn A c xc nh cho mc A (tt c b mt ca khu vc v thit b) c
p dng cho tt c sn phm.
5.5.2. Tiu chun B
Tiu chun chp nhn B c xc nh cho mc B (cc b mt bn ngoi ca cc thit b) c
p dng trong vic tm kim vt cht gy nhim.
Theo tiu chun ny, b mt mc B khng c c qu 10 ln s lng ca cht cn gi li i
vi mc C (cc b mt ca thit b tip xc vi sn phm). LB = 10.LC
5.5.3. Tiu chun C
Tiu chun chp nhn C c xc nh cho mc C (cc b mt ca thit b tip xc vi sn
phm) v c p dng cho cc hot cht.

I: 0.001 ln ca liu iu tr ti thiu hng ngy ca hot cht (mg/ ngy).
J: Liu ti a dng hng ngy cho bnh nhn ca sn phm c sn xut k tip.
K: S liu cho mi l sn phm c sn xut k tip.
S: Tng din tch tip xc vi hot cht v sn phm c sn xut (m
2
)

Trong trng hp khng tnh n cc hot cht c th, c th p dng mt gii hn pht hin chung
l 10ppm tc l khng c c qu 10ppm hot cht A c pht hin trong sn phm k tip. Khi
vic tnh ton cho tng thit b cng nh trn:

hay:
Lng tp nhim ti a (Maximum contamination = MC):
Lng tp nhim ti a ca hot cht c php c trong 100cm
2
thc hin bng phng php
Swab, c tnh theo cng thc sau:

Trong R: H s hi phc ca t dc c tan thp nht (g).
S: C l ca sn phm sn xut sau (g).
T: Tng din tch b mt bn trong ca mu th (cm
2
).

u: Din tch Swab (100cm
2
).

n: S thit b trong dy chuyn sn xut.
5.5.4. Tiu chun D
Tiu chun p dng cho hot cht, t dc v tc nhn v sinh.
Tiu chun chp nhn ny c xc nh cho mc D (Nc thi sau khi ra).
X: nng hot cht c th tm thy trong sn phm k tip (tnh bng ppm).

Trong :
+ F: liu iu tr cn chp nhn c hoc liu c, mt cch tng qut 0.001 F 0.025.
+ DMT: liu iu tr ti thiu hng ngy ca hot cht c thm nh..
+ DMP: liu ch nh ti a hng ngy ca sn phm k tip
Bit X tnh c gii hn nng hot cht trong dung dch trng LD:

Trong : T
min
: c l nh nht ca sn phm nghin cu.

V: th tch ca dung dch trng tnh bng lt.
f: h s hiu chnh nu c l ca sn phm nghin cu
(T
sn phm
) nh hn c l ln nht ca sn phm ny (T
max
)

Bit LD tnh c X:

6. Ti liu thm nh
6.1. cng thm nh
Mt cng thm nh phi c thit lp v ph chun cho tng thit b kho st, trc khi thc
hin vic thm nh.
cng t nht phi gm c:
Mc tiu phi t.
Ngi thc hin v trch nhim.
La chn trng hp xu nht.
S v k hoch ly mu.
Phng php ly mu.
Tiu chun chp nhn.
Chu k thm nh.
Bng ghi kt qu vic thm nh.
6.2. Bo co thm nh
Bo co thm nh c thit lp sau khi thm nh. y l cng c y kt qu v kt
lun.
7. CHU K THM NH
Nu phng php v sinh khng c thay i, tin hnh phn tch mi 2 nm/ ln.
Mt khi phng php v sinh thay i, phi thm nh.
Nhn
Nhn tnh trng thit b

Khi kho st mt s vt, hin tng hay mt qu trnh, ngi ta thng quan st n di hai trng
thi:
Trng thi tnh: Kho st vt hay h vt trng thi cn bng.
Trng thi ng: Nghin cu v ng hc v ng lc hc ca cc qu trnh chuyn ng:
+ ng hc nghin cu s chuyn ng ca vt hay h vt m khng tnh n nguyn nhn gy ra
chuyn ng.
+ ng lc hc kho st nhng quy lut chuyn ng ca vt v nguyn nhn gy ra hoc lm thay
i cc chuyn ng .
Chng ny ny i su vo kho st trng thi ng ca cc qu trnh cng ngh c bn thng gp
trong cng ngh dc phm, ni dung ca n bao gm ba vn chnh:
CHNG 2
CC QU TRNH CNG NGH C BN
TRONG SN XUT DC PHM
Trnh by cc c s l thuyt.
Cc phng php tnh ton cc qu trnh cng ngh.
M t cc thit b c bn.
i su vo kho st cc c s l thuyt ca cc qu trnh i hi phi hc cc mn c s nh: c
l thuyt, c hc cht lu v.v, trong khun kh thi gian v yu cu ca hc phn ny, chng ta s
khng i su vo phn c s l thuyt, c bit l phn ng lc hc ca cc qu trnh, m ch yu tp
trung kho st phn ng hc ca cc qu trnh, ng dng mt s tnh ton qu trnh cng ngh n
gin, m t nguyn l cc thit b c bn nhm mc ch gip cho vic vn hnh, khai thc v la chn
thit b.
Tc pht trin nhanh chng ca k ngh dc i hi phi gii quyt nhng vn khoa hc
phc tp c lin quan n vn thit k, xy dng v sn xut ca cc nh my dc phm. iu cn
phi ch trng l tm ra cc qu trnh cng ngh c hiu sut ti u, nhng cu to my mc cho nng
sut cao v t ng ho thun li.

Bi 6
XAY RY VT LIU

KHI NIM CHUNG
Xay l mt qu trnh c hc lm gim kch thc cc ht rn. Nhng thut ng khc nhau: (p, gi,
phn tn, xay, nghin, tn mn) c s dng ng ngha vi qu trnh, thit b xay sn phm. My xay
c phn loi theo kch thc sn phm c xay: xay th, xay trung bnh, xay mn.
V d: C ht c xay
Xay th: 840mm
Xay trung bnh: 74 840mm
Xay mn: 74mm
Tuy nhin mt my c th to c nhiu c ht khc nhau tu thuc loi li ry s dng.
MC TIU
1. K tn c cc loi my xay thng dng trong ngnh dc.
2. Trnh by c nguyn l cc loi my xay.
3. Phn tch c nh hng ca cc yu t n hiu sut ca qu trnh ry.
4. Bit cch chuyn i c ry gia Dc in Vit Nam v c ry theo USP (mesh).
Qu trnh xay c c trng bng nghin:

Trong : n nghin
D ng knh ca vt liu trc khi xay.
d ng knh ca vt liu sau khi xay.
ng dng ca xay trong sn xut dc phm: Din tch b mt ca mt n v khi lng tng ln
khi gim kch c ht, iu ny s nh hng n hiu qu iu tr v khi vo c th cc ht s c din
tch tip xc vi dch c th tng ln, s rt ngn thi gian ho tan hn cc ht th.
6.1. My xay vt liu
6.1.1. My xay ba
My xay ba dng xay s b v xay nh ln
cui cc vt liu c m khng qu 15%. Cu to ca
n gm c v my, trn trc quay nm ngang c gn
a, trn a gn cc ba lp ng, ba thng lm
bng thp cng khng g. Vt liu a vo my qua
ca cp vt liu (hnh 6.1). Khi trc quay, di tc
dng ca lc ly tm ba ging thng theo chiu hng
tm v p mnh vo vt liu lm cho vt liu v nh
ra. Vt liu sau khi xay c tho qua ry. Ry ny c
th iu chnh thu c sn phm c kch c mong
mun bng cch thay i cc ry c l to nh khc
nhau.

Hnh 6.1. My xay ba

6.1.2. My xay ct
My xay ct gm mt lot cc li dao c gn
c nh vo mt rotor quay theo phng nm ngang,
khi rotor hot ng, cc li dao gn trn rotor c
chiu ngc vi cc li dao gn c nh trn v my
(hnh 6.2). Trong qu trnh xay, vt liu b ct thnh
nhng phn t nh gia hai b li dao. Mt li ry
c gn trn v my v gi li nhng vt liu c kch
thc ln hn l ry thc hin qu trnh ct xay tip
tc cho n khi t c c ht thch hp c th i qua
li ry. My c tc ct cao c bit thch hp cho
xay dc liu.

Hnh 6.2. My xay ct

6.1.3. My xay inh
Khi thng quay, di tc dng ca lc ly tm v do ma st cc bi p st vo thng s c nng ln
mt on theo hng quay n mt cao no , ri chng ri t do theo hnh parabol xung p vo
vt liu cn nghin di, (di tc dng ca trng lc vin bi, lc ny gc nng ln hn gc ri t do).
Nh vy vt liu c nghin nh nh ch st v va p.
Nu tng tc quay ca thng th lc ly tm tng v gc nng cng tng, lc ly tm tng cng s
vng quay ca thng n khi tr s ca n vt qu trng lc ca bi v vt liu nghin th bi s quay
theo thng quay, vt liu khng c nghin, my khng thc hin cng nghin c ch.
Do cn xc nh tc lm vic thch hp bi c chiu cao ri v tc ri ln nht. ng
thi cn kho st t l vt liu v bi, t l dung tch lm vic ca thng trn m bo thit b lm vic
c hiu qu. Qua nghin cu v tnh ton, ngi ta xc nh c rng:

Trong : D: ng knh thng
Lng bi np vo thng chim khng qu 30 35 % th tch thng.
Cu to ca my xay inh gm c 2 a trn mi
a c gn cc hng inh ng tm gi xen k vo nhau
(hnh 6.3). Khi my hot ng, cc hng inh gn trn
2 a c chiu quay ngc nhau, vt liu trt v va
p gia cc hng inh b xay thnh nhng tiu phn
c kch thc thch hp i qua l li ry ra ngoi.

Hnh 6.3. My xay inh

6.1.4. My xay a
Cu to ca my gm c a 1 khng chuyn ng,
a 2 quay nh gn vo mt trc nm ngang 3. a 2 c
th iu chnh qua li thay i khong cch khe h
gia 2 a bng b phn iu chnh, nh ngi ta c
th iu chnh c xay (hnh 6.4).

Hnh 6.4. My xay a

6.1.5. My nghin bi
My nghin bi gm mt thng bng kim loi hay
s, bn trong cha mt phn bi bng kim loi hay bng
s v vt liu cn nghin mn (hnh 6.5).

Hnh 6.5. My nghin bi
Kch thc vin bi (ng knh) ph thuc kch thc ng knh ln ca ht lc np vo v kch
thc ht sau khi nghin, tnh theo cng thc sau:

Trong : + Db: ng knh bi (mm).
+ dt: ng knh ht trc khi nghin.
+ dc: ng knh ht sau khi nghin.
Chiu di (L) so vi ng knh (D) ca thng:
L/D = 1,56 (nghin th) n 1,64 (nghin mn)
6.1.6. My xay keo
Trong mt s cu to my xay keo, thn my c th c bc v tin hnh lm nng hay lm
ngui vt liu khi xay.
6.2. Qu trnh phn loi c ht
phn chia vt liu rn xay thnh tng loi c kch thc gn ging nhau, ngi ta ng dng
phng php ry hay phn loi bng ry.
Tin hnh ry bng thit b ry m phn chnh ca n l li ry. Khi ry, nhng ht c kch thc
nh hn kch thc l li s i qua li ry, cn nhng ht c kch thc ln hn s li trn li, v
nh vy cc ht nh c tch ra.
6.2.1. Ry
Khi ry cc vt liu, ngi ta dng cc li ry lm bng li kim loi (ng, thp khng g) hoc
bng si vi tng hp, si la, si polyme Thng thng kch thc ca li c thit lp trn c s
My xay keo gm mt rotor b mt c rng ca
quay vi tc cao (300 20.000v/s) v phn v
my vi b mt xay hnh cn khe h gia v my
v rotor c th iu chnh khong cch 50
75m.
Trong ngnh dc, my xay keo c dng
x l huyn ph v nh tng, n khng c dng
xay cc vt liu kh. Cht rn c xay s b
c trn vi cht mang dng lng trc khi a
vo my xay keo, p lc gia hai mt my lm cho
phn vt liu dnh v quay theo rotor, lc ly tm s
ay vt liu i qua rotor vo v my. Di tc dng
ca cc lc phn tn cc ht c th xay mn ti 3m
v c th c tun hon tr li nh van 3 chiu. B
mt ca rotor v v my c th nhn. Vi b mt
ca rotor v v my nhn s to thnh mt mng
film vt liu ng nht rt mng, thch hp khi xay
nh tng (hnh 6.6).

Hnh 6.6. My xay keo
nhng quy lut nht nh c quy nh trong cc Dc in, trong ngi ta hay chia loi li
theo kch thc di ca l. Mi h thng hay mt thang gm nhiu ry, c trng bng t l khng i
ca l li loi ny vi l li loi tip theo ngha l bng mt i lng khng i gi l modun.
Ry c l khng phi l vung thng k hiu bng s, c ry quy nh cc nc khng ging nhau.
Dc in Vit Nam III quy nh s c ry theo t chc tiu chun ho quc t ISO da trn c s
chiu rng ca l mt ry (vung) (xem bng1).
Trong cc ti liu k thut quc t hoc ca cc hng nc ngoi thng s dng cch phn loi
theo tiu chun ca USP gi l mesh, trong c trng bng s l li trn chiu di 1 inch. V d:
200 l/1 inch ngha l 200 mesh.
Khi phn tch c ht phi ghi r p dng theo thang tiu chun no hoc ghi c th theo loi c mt
li c p dng.
Cht lng ca qu trnh ry c biu din bi hiu sut ry. Vt liu em ry gm cc ht kch
thc khc nhau, n gm cc ht c kch thc c th lt qua ry v cc ht khng th lt qua ry. Sau
khi ry thu c sn phm nm di ry gm cc ht lt qua li v sn phm nm trn ry gm c cc
ht khng th lt qua mt ry. Thc t khi ry khng phi cc ht c kch thc nh hn l ry u lt
qua, nn lng ht di ry bao gi cng nh hn lng ht c kch thc lt qua ry.
Bng 6.1. C ry theo tiu chun Dc in Vit Nam
Bng 6.2. C ry tiu chun
S ry (mm) C mt ry (mm) ng knh si (mm)
2000 2,000 0,900
710 0,710 0,450
500 0,500 0,315
355 0,355 0,224
250 0,250 0,160
212 0,212 0,140
180 0,180 0,125
150 0,150 0,100
125 0,125 0,090
90 0,090 0,053
75 0,075 0,050
45 0,045 0,032
S C mt ry
mm m
2 9,52 9520
4 4,76 4760
Hiu sut ry
T s lng ht qua ry vi lng ht c th lt qua ry ta gi l hiu sut ry, biu din bng %.

G khi lng vt liu ban u cho vo ry, kg.
G
1
khi lng sn phm di ry, kg.

a lng ht c th lt qua ry lc ban u, %.
E Hiu sut ry (%) tnh theo cng thc ty thuc kiu v cu to ry, hiu sut thng thay i
khong 60 75%, ti a 90%.
Nhng yu t nh hng n hiu sut ry:
1. Hnh dng v kch thc l ry, hnh dng vt liu.
2. B dy lp vt liu trn ry.
3. m vt liu.
4. Vn tc v c trng vt liu trn ry.
Dng v kch thc l ry l mt trong nhng yu t quyt nh v trong mi trng hp c th phi
chn l ry theo hnh dng ht vt liu. ry ht vt liu c dng hnh cu ngi ta dng ry l hnh
bu dc, hnh ch nht, hnh vung. Ht c dng hnh cu i qua li d hn cc ht khc. Thng
ngi ta chn kch thc l li ln hn mt cht so vi kch thc ht cn phi i qua.
B dy lp vt liu trn ry nh hng n cht lng qu trnh ry ch, khi lp vt liu trn ry
dy th nhng ht nh nm trn mt c th khng lt qua l ry m xung di. V vy, lp vt liu
cng mng th ry lm vic cng c hiu qu.
Cn phi cho nguyn liu vo ry mt cch u n. Nu tip nguyn liu khng u v cp mt
8 2,38 2380
10 2,00 2000
20 0,84 840
30 0,59 590
40 0,42 420
50 0,297 297
60 0,250 250
70 0,210 210
80 0,177 177
100 0,149 149
120 0,125 125
200 0,074 74
cch gin on vo ry nhng m ln vt liu em phn loi, th iu kin lm vic ca ry s km.
S la chn vn tc i qua ry c mt gia tr quyt nh. Vn tc cng nh th cng c nhiu ht i
qua l v hiu sut ca ry cng ln. nhng vn tc b qu th nng sut ca ry s thp. V th trong
tng iu kin c th khi la chn vn tc cn phi tnh n c hiu sut v nng sut ca ry.
c tnh chuyn ng ca ry v on ng chuyn ng ca ht vt liu trn ry cng ng mt
vai tr quan trng. ng cng di, hiu sut ca qu trnh ry cng cao. S tng on ng i ca ht
vt liu trn ry cho php tin hnh ry vi vn tc nh khi lp vt liu mng, iu to iu kin
tng hiu sut ry. S trt nh nhng v t do ca vt liu theo b mt ry lm cho nhng ht nh nm
lp trn cng khng tip xc vi l v i ra khi ry cng vi sn phm trn ry. V vy, tt nht l
phi lc vt liu trn ry, iu c ng dng trong phn ln cc cu to hin i ca ry.
Vi s tng m vt liu em phn loi, iu kin ry ht nh s km i bi v chng s kt li vi
nhau to thnh cc v do c gi li trn ry.
6.2.2. Cu to ry
Theo nguyn l lm vic ngi ta chia ry lm 3 loi chnh:
1. Ry th cng.
2. Ry lc.
3. Ry rung.
Ry th cng c cu to gm mt khung hnh tr trn pha di c gn cc li ry bng si kim
loi, si vi hoc si tng hp c kch thc l ry khc nhau.
Ry lc cu to gm mt hp ch nht trong lp li l. Ry chuyn ng dao ng nh bnh xe
lch tm hay c cu cam (hnh 6.7a).
Ry rung l loi ry dn c thay th cho ry hnh thng (hnh 6.7b), khc vi ry lc, trong ry
rung khung chuyn ng c di khng i, ry rung c c trng bng s thay i ca bin
chn ng. Ty theo phng php truyn rung ng cho ry ngi ta chia ra ry rung qun tnh, ry
rung p, ry rung in t.

Hnh 6.7. Cc loi ry

CU HI LNG GI * CHN CU NG NHT
1. Sn xut nh tng, nh dch s dng:
a) My xay inh;
b) My xay bi;
c) My xay keo;
d) b v c.
2. Hiu sut ry khng ph thuc:
a) dy lp vt liu trn ry;
b) m vt liu;
c) Vn tc v t trng ca vt liu trn ry;
d) Tt c u sai.
3. Tc chuyn ng ca ht vt liu trn ry:
a) Cng nhanh cng tt;
b) Cng chm cng tt;
c) Vn tc chuyn ng nh, ng i ca ht cng di cng tt;
d) Khng cu no ng.
4. My xay mn cho c ht:
a) 840m;
b) 300 840 m;
c) 100 300 m;
d) <74m.
5. Kch c ht trong qu trnh xay ch ph thuc:
a) Loi my c s dng;
b) Loi vt liu c xay;
c) Loi li ry c lp vo my xay;
d) Khng cu no ng;
e) C a, b, c u ng.
6. Di phn b c ht sau xay ph thuc vo:
a) Loi my xay;
b) Loi vt liu c xay;
c) Loi li ry c lp vo my xay;
d) Tc np vt liu khi xay;
e) Tt c u ng.
7. Mun tng tc ry:
a) Tng tc chuyn ng ca ht vt liu trn ry;
b) Tng tc ca my ry;
c) Dng tay ch vt liu xung mt ry;
d) Khng cu no ng.
8. Mun tng hiu sut ry:
a) Tng tc ry;
b) Np nhiu nguyn liu ln ry;
c) Np u n mt lp vt liu khng qu dy ln ry;
d) iu chnh cho vt liu chuyn ng vi mt tc nh v lp vt liu mng.
9. Trong xay ry, c ht trung bnh c kch thc trong khong:
a) Ln hn hoc bng 1200m;
b) Ln hn hoc bng 850m;
c) T 100 840m;
d) Nh hn hoc bng 75m.
10. Trong quy trnh xay, di phn b c ht khng ph thuc vo:
a) Tc np nguyn liu vo my xay;
b) Cht lng vt liu a vo xay;
c) Kch c l ry;
d) My xay ca hng no ch to.
11. Ry c c l mt ry 10mesh (tnh theo tiu chun USP) tng ng vi c s mt ry tnh theo
tiu chun quc t l:
a) 2000m; b) 1000m;
c) 4000m; d) 500m.
12. Trong mt quy trnh xay c th, mc rng hp ca di phn b c ht ph thuc vo:
a) Loi my xay;
b) Loi li xay;
c) Mc hin i ca my xay;
d) Tc np vt liu vo my.
13. My xay bi lm vic ti u khi:
a) Bi c kch thc ln;
b) Bi c kch thc thch hp;
c) My quay tht nhanh;
d) Bi c chiu cao ri v tc ri ln nht;
e) b, d: ng.

TI LIU THAM KHO
1. KAXATKIN, Nhng qu trnh v thit b c bn ca ngnh cng ngh ho hc, tp 3, NXB Gio
dc H Ni, 1996.
2. LEA v FEBIGER, The theory and Practice of industrial pharmacy, Philadelphia, 1996.
3. S tay qu trnh v thit b cng ngh ho cht, tp 2, NXB Khoa hc v k thut H Ni, 1978.
4. Remington: The science and practice of pharmacy, Alfonso R Gennaro, 20
th
edition.

Bi 7
KHUY TRN VT LIU

Khuy trn c ng dng rng ri trong cng nghip dc ch bin huyn ph, nh tng v
cc hn hp rn, cng nh lm tng cng qu trnh chuyn khi v trao i nhit. Ty theo mc
ch t c ca ch phm v mi trng tin hnh sn xut m ngi ta la chn phng php v
thit b khuy ph hp.
Khi la chn phng php khuy trn v iu kin ca thit b phi ch n trng thi lin kt ca
vt liu em khuy trn. Hai trng hp ph bin:
Khuy trn trong mi trng lng.
Khuy trn trong mi trng rn, xp, nho.
MC TIU
1. Nu c cc ng dng ca qu trnh khuy trn trong cng nghip dc.
2. Phn bit c cc qu trnh khuy trn theo trng thi lin kt ca vt liu.
3. Trnh by c nguyn tc cu to ca thit b khuy.
4. K tn cc dng cnh khuy v phm vi ng dng ca mi loi.
5. Phn tch c cc yu t trong ch thy ng lc ca thit b khuy.
6. Phn tch c ch cng ngh khuy.
7. Trnh by c nguyn l trn hi chuyn.
8. Trnh by c ch trn trong thng trn v cc yu t nh hng n hiu qu qu trnh trn.
7.1. Khuy trn mi trng lng
Trong cng ngh dc thng phi thc hin cc qu trnh lin quan n mi trng cht lng, vi
s phn b tng i ng u v vt cht v nhit , cc yu cu c th p ng c nh khuy
trn mi trng lng.
Phng php khuy c hc c thc hin bng cc cch khuy khc nhau t cc mc ch sau
y:
Thc hin qu trnh thy c: to nh tng, huyn ph, ho tan, ng ho.
Thc hin qu trnh nhit: c c dung dch, un nng, lm ngui.
Thc hin cc phn ng ho hc.
Thc hin cc phn ng sinh hc.
Nh vy khuy mi trng lng, trong :
+ Pha lin tc l mt cht lng.
+ Pha phn tn c th l: pha lng, pha rn hoc pha kh.
Khuy cht lng l cung cp nng lng to mt dng chy thch hp trong thit b nhm p
ng cc yu cu nu trn.
Qu trnh khuy c th thc hin trong thit b gin on hoc thit b lin tc theo yu cu ca mt
cng ngh sn xut c th, iu kin ca mi trng khuy trn c xc nh bi:
Nhit .
p sut.
Nng pha phn tn.
Do vy thit b khuy c th thc hin dng kn hoc dng h. Thit b khuy thng c ch to
dng hnh tr thng ng, tuy nhin cng c trng hp p dng thit b khuy nm ngang.
7.1.1. Nguyn tc cu to thit b khuy
Mt cch tng qut, thit b khuy gm cc b phn ch
yu sau (hnh 7.1): Thng khuy (1) hnh tr vi y trn
hoc hnh nn, pha trn y np (3) ghp vi thn (2) bng
bch theo ng tm ca thng lp trc khuy (10) vi cnh
khuy (11). Trc khuy thng xuyn qua np v c bt
kn bi hp m (4), truyn chuyn ng cho trc khuy t
ng c (7) qua hp gim tc (6) to tc thch hp cho
cnh khuy. Vic tho v lp trc khuy thng qua khp ni
(5). Thng c gn tai (12) nh bu lng gn vo chn
(13). Thc hin nhp liu qua ca (8) trn np thit b, c khi
ngi ta b tr ca sa cha v ca quan st (9).
Trong thc t, thit b khuy c thit k v ch to rt
a dng v kiu v hnh dng, ty thuc vo mc ch s
dng. Thit b khuy c th ch to dng h tc l khng c
ngn cch vi mi trng bn ngoi. Trong trng hp thit
7.1.2. Cc dng cnh khuy

Hnh 7.2. Cc loi cnh khuy:
a) Loi tm (bn) < 50 cP, n 20 80 vng/pht
b) Mi cho bn
c) Mi cho hai thanh thng < 50 cP, n 20 80 vng/pht
d) Mi cho thanh t cho < 500 cP
b lm vic vi iu kin nhit v p sut khc vi mi
trng kh quyn th phi ch to dng thit b kn, ngha l
c s ngn cch vi mi trng bn ngoi. Trc khuy lp
vo thit b c th b tr dng nghing hoc thng gc. Do
nhu cu ca qu trnh cng ngh, thit b khuy c th b tr
thm cc b phn khc nhau nh: ng dn kh, o nhit ,
dn ng truyn nhit

Hnh 7.1. S cu to thit b
e) M neo (ch U) = 10 1000 P
f) M neo ghp
g) Chn vt < 80 cP, n = 400 1800 vng/pht
h) Tuc bin kn < 150 P
l) Loi a rung ng
m) Loi mi cho c truyn ng hnh tinh
n) Sc kh
k) Sc kh tun hon
Khuy l qu trnh to dng chuyn ng ca khi cht lng trong thit b nh cc cnh khuy. V
kt cu cc dng cnh khuy c nhiu dng nhiu kiu khc nhau (hnh 7.2). Tuy nhin, theo quan im
v tc quay, ngi ta chia cc cnh khuy thnh hai nhm chnh:
1. Nhm cnh khuy tc nhanh.
2. Nhm cnh khuy tc chm.
Nhm cnh khuy tc nhanh gm: Bn 2 cnh (mi cho), bn 3 cnh, bn 6 cnh, chn vt,
tuc bin kn, tuc bin h.
Nhm cnh khuy tc chm: m neo, cnh khuy khung, cnh khuy vis, cnh khuy mi cho.
7.1.3. Ch thy ng lc trong thit b
7.1.3.1. Phng chuyn ng
Mi kiu cnh khuy khi lm vic s to ra dng chuyn ng khc nhau. s chuyn ng ca cht
lng c th xem hnh 7.3.

Hnh 7.3. Hng chuyn ng chnh ca dng cht lng trong khi khuy
Theo phng tip tuyn (a)
Theo phng ca trc (b)
Theo phng bn knh (c)
Dng cht lng chuyn ng trong thng khuy c nh hng nhiu n qu trnh khuy. Qua thc
t ngi ta nhn thy rng, dng chuyn ng theo phng trc (ln xung) thch hp cho qu trnh ho
tan cc cht rn v dng chuyn ng theo phng bn knh (qua li), thch hp cho qu trnh trn kh
vi lng hoc lng vi nhau. i vi chuyn ng theo phng bn knh c bit ch n nh hng
ca s khc nhau v nht gia hai cht lng.
7.1.3.2. S to phu (parabol)
Trong qu trnh khuy ngi ta thng thy xut hin nhiu
t lch tm cnh khuy vo b khuy, t nghing hoc t nm ngang, lp thm tm chn trn
thnh (hnh 7.5).

Hnh 7.5. Cc kiu t cnh khuy
7.1.2.3. Ch cng ngh khuy
Trong phn ny cp n ch cng ngh ca qu trnh c hc nh: ho tan, to huyn ph hay
nh tng.
a) C ch ca qu trnh ho trn
Trn hnh 7.6: biu din s bin i nng pha phn tn trong hn hp theo thi gian khuy. Gi
s ti thi im t
1
a pha phn tn vo pha lng, nng hn hp tng vt ln:

Trong : + G Khi lng pha phn tn ho trn, kg.
ch xoy ln trn b mt v chuyn ng trn ca cht lng
i khi b hn ch l do s mt mt nng lng nhiu v s to
bt trong khi khuy. Lm xoy parabol (hnh 7.4) hnh thnh v
tn ti s lm gim hiu qu khuy trn do t phu, kh c th
thm nhp vo mi trng lng (to bt), i khi cn c tc dng
ngc li l lm xut hin kh nng phn ly (tc dng lc ly tm).
trnh kh nng to thnh lm xoy parabol trong thng
khuy, ngi ta thng dng nhng phng php sau:
Hnh 7. 4. Lm parabol trong bnh
khuy
+ V Th tch cht lng trong thit b, m
3
.

+ C
tb
Nng trung bnh ca pha phn tn.

Tuy nhin nng pha phn tn trong giai on u ca qu trnh khuy trn phn b cn cha
ng u, ch nhiu, ch t. Ti thi im t
2
,

khi kt thc qu trnh khuy, nng ca hn hp gn t
n gi tr nng trung bnh cho trc:

Trong : + C Nng pha phn tn ti thi im ly mu t
i
.

+ C Chnh lch nng pha phn tn ti thi im ly mu so vi nng trung bnh.
Nh vy, thi gian khuy cn thit c xc nh: t = t
2
t
1
.

Hnh 7.6. S ph thuc nng vo thi gian khuy
t cng l thi gian cho s khuy trn t n ng u ca pha phn tn vo mi trng
phn tn cc v tr khc nhau ti cc thi im khc nhau.
Hiu qu ca qu trnh khuy c nh gi bng i lng mc ng nht. Mc ng nht
( ) ca hn hp c nh ngha nh t s gia nng ca hn hp v nng trung bnh cho trc:

Qu trnh khuy trn th hin ch, mun 1 v 0 th t
Thc hin qu trnh khuy t hiu qu ty thuc vo loi cnh khuy, quan h kch thc hnh hc
v ch thy ng lc trong thit b.
b) Ch cng ngh khuy
Qu trnh thy c c thc hin to ra cc hn hp vi mc ng nht cn thit c gi l s
ng ho. S ng ho nhm phn b tng i ng u trng vt cht v trng nhit .
Ch cng ngh ca qu trnh ho tan, huyn ph ho hoc nh tng ho l to ra mt ch
thy ng lc thch hp, trong khong thi gian ngn nht, chi ph nng lng thp nht t c
ng nht cao.
Mun vy cn quan tm nghin cu cc c tnh s bin i mi trng khuy:
Khi lng ring ().
nht ().
Kch thc (ng knh) cc phn t pha phn tn (d
p
).

iu kin tn ti vng bn ca hn hp. S tng quan v khi lng ring ca hai pha hoc hai
cu t ho trn c nh hng ln n hn hp, thng qua gi tr tc lng hoc ni ca phn t.
7.2. Khuy trn trong mi trng ht rn ri v bt nho (hn hp)
Trong cng nghip bo ch cc dng thuc dng rn: thuc bt, thuc vin, cng ngh khuy trn
trong mi trng rn ri v bt nho c s dng rng ri.
Cn c vo cu to ca cc thit b trn cc ht rn xp v bt nho c th chia thnh nhng
nhm sau:
Thit b trn c cc cnh quay.
Thng trn.
7.2.1. Thit b trn c cc cnh quay
trn cc vt liu dng bt ri v bt nho mm, c hoc khng thm cht lng, ngi ta s dng
rng ri my trn c cnh trn (mt hoc hai cnh). Trong thit b ny, qu trnh tin hnh theo nguyn
tc trn hi chuyn v ng thi chia ct khi vt liu (hnh 7.7).
Trn hnh 7.7 m t s ca my trn mt
cnh khuy un cong c bit trong thit b trn
hnh lng mng, khi cnh khuy quay 180
o
, di
nh hng p lc ca cnh, khi vt liu b p
ln yn mng v b p cht, khi phn vt liu i
ra khi phm vi tc dng ca phn th nht ca
cnh khuy ny th c phn th 2 ca cnh
khuy cun ly, qu trnh cng xy ra nh th
i vi khi vt liu ang i n yn ca phn
th hai ca cnh khuy, nh vy tc l c s tin
hnh phn chia vt liu. Cng vi hin tng
ny, nhng lc tc ng t cnh khuy hng
vo trong khi vt liu, im t ca cc lc thay
i t t, kt qu t c s trn bng hi
chuyn. Trong cc my thit k hai cnh trn.
trnh hin tng cc khi vt liu ng cht, do
yn gp nhau sau mi vng quay ca cc cnh,
th cc cnh phi khng cng mt s vng
quay nh nhau. ng thi t s ca cc s vng
quay khng phi l mt s nguyn (hnh7.8).
Hnh 7.7. S thit b nho trn
Qu trnh khuy trn trong thit b loi ny tin hnh cng vi s mit cc b khi vt liu v xy ra
nhng qu trnh khc ngoi yu cu. Tng ng vi chc nng, trn nhng thit b loi ny thng c
gi l my nho trn.

Hnh 7.8. Cc kiu cnh khuy trn
7.2.2. Thng trn
Thng trn bnh thng gm c mt thng cha c dng hnh hc khc nhau, cc dng thng dng
l: hnh ch v, hnh khi lp phng, hnh tr, hnh cn hai u cc thng cha c quay nh 1 trc
nm ngang (hnh 7.9).
C ch trn trong thng trn:
Qua cc nghin cu vic trn cht rn din ra bi s kt hp ca mt hay nhiu c ch:
a) Trn i lu
C ch ny c xem nh l gn ging s chuyn khi trong khuy trn cht lng. Trn i lu ph
thuc vo loi my c s dng, n xy ra bi s o ngc (nghch chuyn) khi vt liu bng cc
cnh, mi cho, bng trc quay hoc bng mt phng php no di chuyn mt khi vt liu
tng i ln t phn ny ca khi bt ti phn khc.
b) Trn trt
Cc mt phng trt to thnh nh l kt qu ca cc lc trong khi ht, n ph thuc vo c tnh
chy ca bt. Chuyn ng trt c th din ra mt cch n gin hoc lm tng s chy thnh tng lp.
Khi chuyn ng trt xy ra gia cc vng vt liu c thnh phn khac nhau v song song vi b mt
phn cch lp s lm gim phm vi phn cch bng cch lm mng i nhng lp khng ging nhau.
c) Trn khuch tn
Trn khuch tn l ni n s pht sinh khi c s chuyn ng ngu nhin ca cc ht trong khi bt
trn gy thay i v tr tng i vi nhau. S thay i v tr ca cc ht nh vy l dn n kt qu
gim cng phn ly. Trn khuch tn xy ra mt phn cch ca cc vng khng ging nhau chu s
trt v kt qu l trn trt, s khuch tn cng c th xy ra bi mt dng rung ng no m kt
qu s di chuyn v tr tng i gia cc ht vi nhau.
Cc c tnh chy chung ca bt xc nh mc trn d dng ca cc ht lc khi u. Ngha l s
chuyn khi ca khi bt d dng nh th no, khi bt p xung nh th no? cho php trn
k cc ht c th gim cng phn ly cc ht trong mt chu trnh thi gian ngn nht.
C ch phn ly:
Cc cht rn dng ht hng ti s phn ly bi cc tc dng khc nhau v c ht, t trng, hnh dng
v cc c tnh khc ca ht.
Qu trnh phn ly c th xy ra trong qu trnh trn cng nh trong cc cng on tip theo nh dp
vin, ng nang.
Hiu qu trn:
Hiu qu trn ph thuc vo tc quay ca thng trn. Tc quay qu chm khng to ra c
cng chuyn ng p xung hay chy xung nh thc nh ta mong mun hoc khng to ra
c tc trt cao. Mt khc khi chuyn ng qu nhanh s dn n vic to ra lc ly tm hay phn
ly bt ra pha thnh thng trn. Tc quay ti u ph thuc vo hnh dng, kch thc ca thng trn.
Thng th tc khong 30 100 v/pht.
Hiu qu trn ph thuc vo c tnh loi vt liu c trn, lng vt liu c np vo thng trn.

Hnh 7.9. Cc loi thng trn
a) Thng trn hai u hnh cn; b) Thng trn ch V.
Thi gian trn: Thi gian qu ngn dn n hu qu trn khng u. Thi gian qu di s lm trn
cnh cc ht d dn n phn ly.
Trong qu trnh trn c th xut hin hin tng vn cc do hin tng tch in ca ht trong qu
trnh trn, c th x l bng cch hi tng m ca bt.

CU HI LNG GI * CHN CU NG NHT
1. Pha lin tc trong khuy trn cht lng l:
a) Dung mi;
b) Cht rn;
c) Cht kh.
d) Dc cht ho tan.
2. Cnh khuy tc nhanh l:
a) Cnh khuy vis;
b) Cnh khuy mi cho;
c) Cnh khuy tuc bin;
d) S phn chia ny mang tnh tng i.
3. Pha ch dung dch tim truyn NaCl 0,9% dng loi:
a) Tuc bin;
b) Chn vt;
c) M neo;
d) Khung.
4. Pha ch nh tng s dng loi cnh khuy:
a) Mi cho;
b) Kiu tm;
c) Tuc bin;
d) M neo.
5. Phng chuyn ng ca cnh khuy chn vt theo:
a) Phng tip tuyn;
b) Phng ca trc;
c) Phng bn knh;
d) Khng cu no ng.
6. Phng chuyn ng ca cnh khuy tuc bin theo:
a) Phng tip tuyn;
b) Phng ca trc;
c) Phng bn knh;
d) Phng ca trc v phng bn knh.
7. S hnh thnh lm parabol trong khi khuy cht lng:
a) Gip ho tan nhanh cht rn do tc khuy cao;
b) Hn ch s phn ly khi ho tan hai cht lng c t trng khc nhau nhiu;
c) Lm cho kh xm nhp vo mi trng khuy trn to bt;
d) Tng cng din tch tip xc vi khng kh gip tng qu trnh trao i nhit;
8. Ph lm xoy parabol bng cch:
a) t cnh khuy chnh gia tm thng khuy;
b) t nghing cnh khuy;
c) Gim tc khuy;
d) Thay loi cnh khuy;
9. Hiu qu khuy trn ph thuc vo:
a) Thi gian khuy trn;
b) Kiu cnh khuy;
c) Bn cht moi trng khuy trn;
d) C a v b.
10. ng lc hc ca qu trnh khuy trn trong mi trng lng khng ph thuc vo:
a) Khi lng ring ca pha phn tn;
b) nht ca pha lin tc;
c) Kch thc tiu phn cc hot cht cn ho tan;
d) Bn cht ho hc ca pha lin tc.
11. trn mt hn hp bt kh, chn loi thit b:
a) Thit b nho trn (kneader);
b) Thit b trn hnh ch V;
c) Thit b trn c cnh khuy m neo;
d) My trn c cnh khuy chn vt.
12. Thit b trn c cnh khuy hnh ch Z hot ng theo nguyn tc:
a) i lu;
b) Hi chuyn;
c) Trt;
d) Trn khuch tn.
13. S phn ly ht sau qu trnh trn kh l do:
a) Phn b c ht;
b) T trng ht;
c) Thi gian trn di;
d) Khi lng m trn ln.
14. Cng ngh khuy trn nghin cu v:
a) S bin i ca pha phn tn trong qu trnh khuy trn;
b) Cu to ca thit b khuy;
c) Hnh dng cc loi cnh khuy;
d) Khng cu no ng;
15. Khuy trn l:
a) Qu trnh ho tan;
b) Qu trnh ho hc;
c) Qu trnh phn tn;
d) Khng cu no ng.
16. Qu trnh khuy c th thc hin trong thit b:
a) Thng khuy h;
b) Thng khuy c p sut thp;
c) Thng khuy c p sut cao;
d) Cu no cng ng.
17. iu kin ca mi trng khuy trn c xc nh bi:
a) Nhit ;
b) p sut;
c) Nng pha phn tn;
d) C a, b, c.
18. Cnh khuy tc chm c s dng :
a) Khuy trn trong pha ch thuc tim;
b) Khuy trn trong sn xut thuc m;
c) Khuy trn trong mi trng c nht ln;
d) Khng cu no ng.
19. Phng chuyn ng ca cnh khuy kiu khung bn l:
a) Phng ng knh;
b) Phng ca trc;
c) Phng bn knh;
d) Phng tip tuyn.
20. Pha ch hn dch chn loi cnh khuy no l thch hp:
a) Cnh khuy khung bn;
b) Cnh khuy chn vt;
d) Cnh khuy m neo;
21. Ho tan cht rn trong dung dch, chn loi cnh khuy c phng chuyn ng thch hp l:
a) Phng bn knh;
b) Phng ca trc;
c) Phng tip tuyn;
d) Phng ca trc v phng bn knh.
22. Hin tng to phu (Parabol) trong khi khuy lm kh xm nhp vo mi trng lng to bt.
Mun ph bt phi x l bng cch:
a) Ngng khuy;
b) Khuy chm;
c) Gim sc cng b mt mi trng khuy trn;
d) Thay cnh khuy khc.
23. Mt qu trnh khuy trn ti u l qu trnh c:
a) Thi gian trn ngn nht;
b) Tiu tn t (nng lng cho khuy trn) nht;
c) t ng nht cao nht;
d) t ng nht v thi gian trn thch hp nht.
24. C ch no khng xy ra trong thng trn:
a) i lu;
b) Trt;
c) Khuch tn;
d) Hi chuyn.
25. Hiu qu ca qu trnh trn trong thng lp phng ph thuc:
a) Thi gian trn;
b) Khi lng m trn;
c) Tc trn;
d) a v b.
26. Khi trn t dc trn trong thng trn, cm c hin tng chy khng u l do:
a) Thi gian trn khng ;
b) T trng cc loi bt trong hn hp qu chnh lch;
c) Khi lng m trn qu ln;
d) Tt c cc nguyn nhn trn.
27. Mun tng hiu qu qu trnh khuy ho tan:
a) Chn cnh khuy thch hp, hin i;
b) Chn cnh khuy chn vt;
c) Khuy khng to lm xoy parabol;
d) Tng cng din tch b mt tip xc gia pha lin tc v pha phn tn.
28. Qu trnh nho trn bt ti u trn thit b trn theo nguyn l hi chuyn ph thuc:
a) Mc hin i ca my trn;
b) Thi gian nho trn;
c) Mc ng nht v chc ca khi bt;
d) tng t trng ca khi bt.
29. duy tr tnh ng nht ca dch bao trong thng cha dch bao phim chn loi cnh khuy:
a) Cnh khuy bn;
b) Cnh khuy chn vt;
d) Loi no cng s dng c.
30. pha c mt hn hp ng nht hai cht lng khng ho tan vo nhau chn loi cnh khuy:
a) Cnh khuy kiu m neo;
b) Cnh khuy kiu hnh tinh;
c) Cnh khuy kiu chn vt;
d) Cnh khuy kiu tuc bin.
31. trnh to lm xoy parabol khi pha ch mt dung dch c nht cao:
a) S dng cnh khuy kiu chn vt;
b) t cnh khuy lch tm;
c) Tng tc khuy ln 3000 vng/pht;
d) Gim bt nht ca dung dch bng ho cht.

TI LIU THAM KHO
1. KAXATKIN, Nhng qu trnh v thit b c bn ca ngnh cng ngh ho hc, tp 3, NXB Gio
dc H Ni, 1996.
3. Michael E.Aulton, Pharmaceutics: The Science of Dosage Form Design
4. Nguyn Vn La, Cc qu trnh v thit b c hc, Quyn 1: Khuy Lng lc
5. S tay qu trnh v thit b cng ngh ho cht, tp 2, NXB Khoa hc v k thut. H Ni, 1978.

Bi 8
SY VT LIU

8.1. Khi nim chung
Sy l qu trnh tch pha lng ra khi vt liu bng phng php nhit. Phi nng l bin php sy
t nhin rt n gin, tuy nhin phng php ny b hn ch v tn din tch sn phi v thi gian, ph
thuc thi tit v mi trng. V vy trong cc lnh vc sn xut ca nn kinh t v x hi ngi ta s
dng cc thit b sy c ch to theo cc cng ngh sy khc nhau.
Kt qu qu trnh sy, hm lng cht kh trong vt liu tng ln. iu c ngha quan trng
trn nhiu phng din khc nhau: Tui th ca sn phm, n nh, cc ch tiu c l v ni chung
cc vt liu sau sy u c gim gi thnh vn chuyn.
Do cc ngha nu, i tng ca qu trnh sy tht a dng bao gm nguyn liu, bn thnh
phm, thnh phm trong cc giai on khc nhau ca qu trnh sn xut v ch bin.
Tht ra sy l qu trnh cng ngh phc tp v i khi n thng ng vai tr quyt nh trong quy
trnh sn xut. V d sn xut thuc vin nn, vin bao.
Nguyn tc ca qu trnh sy, l cung cp nng lng nhit bin i trng thi pha ca cht lng
trong vt liu thnh hi. Hu ht cc vt liu trong qu trnh sn xut u cha pha lng l nc v
ngi ta thng gi l m. Nh vy trong thc t c th xem sy l qu trnh tch m bng nhit.
Vic cung cp nng lng nhit cho vt liu trong qu trnh sy c tin hnh theo cc phng
php truyn nhit bit. Cc tn gi tng ng: cp nhit i lu gi l sy i lu, cp nhit bng dn
nhit gi l sy tip xc, cp nhit bng bc x gi l sy bc x. Ngoi ra cn cc phng php sy c
bit: Sy bng dng in cao tn, sy trong trng sng siu m, sy ng kh, v.v
Ngi ta ni rng sy l mt qu trnh in hnh v qu trnh khng thun nghch v khng n nh,
trong hm m ca cc vt liu bin i theo c khng gian v thi gian, m bn thn qu trnh t tin
dn n trng thi cn bng. Trong cc thit b sy, lng nhit m vt liu nhn c c th biu din
theo phng trnh:
Trong :
MC TIU
1. Phn tch c c ch qu trnh sy.
2. Phn bit c cc thng s ca trng thi khng kh m.
3. Phn tch c cn bng vt liu trong qu trnh sy v trng thi cn bng nhit m ca vt
liu.
4. Phn tch c cc giai on ca ng cong sy.
5. Phn tch c cc yu t nh hng n tc sy.
6. Phn loi qu trnh sy v thit b sy.
7. Trnh by s 3 loi thit b sy: sy i lu, sy tng si, sy phun.
dQ =
q
F (t
x
t
b
)

(8.1)
+
q
H s truyn nhit cho vt liu.

+ F B mt truyn nhit hay b mt bay hi ca vt liu.
+ t
x
Nhit trong phng sy.

+ t
b
Nhit bay hi ca m.

+ dQ Lng nhit m vt liu nhn c trong thi gian dt.
Lng nhit ny mt phn lm bay hi m, mt phn t nng vt liu v c gi l lng nhit
hu ch cn cho qu trnh sy.
Tc sy: Lng m bay hi trong mt n v thi gian.
Cng sy: Lng m bay hi t 1m
2
b mt vt liu trong 1 gi (jm, kg/m
2
.h) (cng sy
chnh l tc sy tnh cho mt n v b mt bay hi).
Theo nguyn l ca nhit ng lc hc, cng sy cn c gi l dng m v c biu din
tng qut:
Trong : j Mt dng.
X ng lc ca qu trnh.
L H s ng lc hc, ph thuc vo tnh cht ho l ca vt liu.
ng lc ca qu trnh sy c th l: Gradien hm m, gradien nhit , gradien p sut ton phn
hoc gradien p sut thm thu trong vt liu.
Theo phng trnh (8.2) mun tng cng qu trnh sy c th tng cng h s ng hc L, hoc
tng ng lc X. Thng thng trong qu trnh sy ng lc qu trnh b gii hn bi iu kin cht
lng trong vt liu. V vy mi c gng trong nghin cu u nhm ci thin h s ng hc. Cng c
nhng cng trnh nghin cu nhm tm kim cc gii php k thut, trong s kt hp tc ng ca cc
dng ng lc khc nhau. Ni chung cc cng trnh nghin cu v sy u hng n cc bin php lm
th no cho chi ph t nng lng nht, thu c cc sn phm cht lng tt nht trong cc thit b c
nng sut cao nht.
nh gi hiu qu ca mt thit b sy, ngi dng i lng hiu sut nhit hu ch (k hiu )
c biu din nh l t s:

C ch ca qu trnh sy trong thit b c din t bi 4 qu trnh cn bn sau (hnh 8.1):
j = LX (8.2)
1. Dng nhit q
m
cp cho b mt vt liu.
2. Dng nhit q dn t b mt vo vt liu.
8.2. Mi trng khng kh m
8.2.1. Trng thi khng kh m
Khng kh kh tuyt i thng c thnh phn khng i theo th tch, bao gm 78% nit, 21% oxy
v 1% kh tr. Trong khng kh bao gi cng c mt hi nc vi liu lng khc nhau. Nh vy hn
hp ca khng kh v hi nc c gi l khng kh m.
8.2.2. Cc thng s vt l ca khng kh m
a) Nhit bu kh: (t
k
,
o
C)

Ch r mc t nng ca khng kh. o t
k
bng nhit k.

b) Nhit bu t: (t
,
o
C)

c trng cho kh nng cp nhit ca khng kh, lm bay hi nc cho n khi khng kh bo
ho hi nc. Vy t
l nhit bay hi ca nc vo khng kh, nu t

k
= t
s bay hi ca nc s
ngng li. Qu trnh bay hi ca nc vo khng kh thc hin trong iu kin on nhit:
t
k
= t
k
t

o nhit bu t hoc bng m k hoc bng nhit k bc vi t.
c) Nhit im sng: (t
s
,
o
C)

L nhit ca khng kh m tng ng vi trng thi bo ho ( = 1). Vy nhit im sng
ch r trng thi hon ton bo ho hi nc trong khng kh, nu tip tc gim nhit , s xy ra qu
trnh ngng t hi nc thnh nc.
d) m tuyt i ca khng kh: (
h
, kg/m
3
)

L lng hi nc cha trong 1m
3
khng kh m, v mt tr s n bng khi lng ring ca hi
nc trong khng kh m. p sut v nhit xc nh m lng hi nc c cha ti a trong 1m
3
khng kh m, ngi ta gi l trng thi bo ho hi nc ca khng kh m, k hiu l:
h
, kg/m
3
.

3. Khi nhn c nhit lng q, dng m J di chuyn t vt
liu ra b mt.
4. Dng m J
m
t b mt vt liu tch vo mi trng xung
quanh.
Bn qu trnh ny th hin bng s vn chuyn bn trong vt
liu v s trao i nhit m bn ngoi gia b mt vt liu v mi
trng xung quanh.

Hnh 8.1. C ch qu trnh sy
e) m tng i (hoc mc bo ho) ca khng kh m:
m tng i l t s gia lng hi nc cha trong 1m
3
khng kh m vi lng hi nc bo
ho ca trng thi khng kh trong cng iu kin p sut v nhit .

Trong :
+ m tng i ca khng kh c tnh bng phn n v hoc bng %.
+ p
h
p sut ring phn ca hi nc trong khng kh nhit ca hn hp kh.

+ p
b
p sut ca hi bo ho nhit ca hn hp kh.

Gi tr ca thay i t 0 1, vi khng kh kh tuyt i p
h

p
h
= 0, nu khng kh hon ton bo
ho hi nc tc l p
h
= p
b
v = 1, nh vy c th vit: p
h
= .p
b

f) Hm m ca khng kh m:
L lng hi nc cha trong 1 kg khng kh kh tuyt i, k hiu l X,

k
Khi lng ring ca khng kh kh tuyt i nhit 30
o
C, p sut 1atm.

Hm m ca khng kh c th tnh bng gram m trong 1kg khng kh kh v k hiu l: d, (g/kg)

g) Khi lng ring ca khng kh m:
Khi lng ring ca hn hp khng kh m bng tng khi lng ring ca khng kh kh v khi
lng ring ca hi m cng nhit .
=
k
+
h
, kg/m
3

Khi lng ring ca khng kh trong iu kin tiu chun:
0
= 1,293kg/m
3

h) Th tch ring ca khng kh m ( ):
Th tch ring ca khng kh m l th tch ca 1kg khng kh kh v khi lng hi nc cha
trong , c ngha l:

i) Entanpy ca khng kh m: (I)
(Entanpy cn gi l hm nhit hoc l nhit lng ring tc l lng nhit cha trong 1kg khng kh
kh).
Entanpy ca khng kh m c xc nh bng tng ca entanpy ca khng kh kh v entanpy ca
hi nc cha trong : I = i
k
+ Xi
h
, j/kg
i
k
Entanpy ca khng kh kh, j/kg.

i
h
Entanpy ca hi nc trong khng kh.

8.2.3. Gin khng kh m
n gin ho vic tnh ton cc thng s vt l ca trng thi khng kh m, ngi ta xy dng
biu I X hoc biu I d c gi l gin khng kh m (hnh 8.2), mang tn gin Ramdin
(1918).

Hnh 8.2. Gin khng kh m
Nguyn tc thnh lp gin I X hoc I d:
th c v theo p sut P = 760mmHg. tin li trong s dng, ngi ta cu to gc hp
thnh gia trc I v trc X l 135
o
trn gin I X.

ng I = const l nhng ng song song vi trc X.
ng X = const l nhng ng thng ng song song vi trc I.
ng nhit khng i l nhng ng nghing c dc tng khi nhit tng.
ng m tng i khng i = const l mt chm ng cong xut pht t mt im trn
th (x = 0, t = 273
o
C). Khi t 99,9
o
C p sut ca hi nc bo ho bng p sut kh quyn
760mmHg. Khi ng = const gn nh song song vi ng X = const.
ng = 100% chia th thnh hai min: Min di l min qu bo ho, khi c mt phn hi
nc trong khng kh ngng li thnh nhng git nc nh dng sng m, min trn ng =
100% l min khng kh trng thi cha bo ho. Qu trnh sy bng khng kh ch thc hin c
min trn.
V d:
Trng thi khng kh m c nhit t = 20
o
C v m = 0,8, hy tm cc thng s vt l cn li
ca trng thi khng kh m .
Gii:
Theo ng t = 20
o
C = const ko n gp ng = 0,8, xc nh c trng thi khng kh m
im A.
T A theo ng X = const ko xung trc honh pha trn tm c d = 12g/kg.
T A theo ng I = const ko di en trc tung, tng ng I = 12kcal/kg.
T A ko song song vi trc tung xung trc honh pha di th c p sut ring phn ca hi
nc P
h
= 14 mmHg. (
190mmH
2
O)

T A ko song song vi ng I = const n gp ng =1, t giao im ny theo ng t =
const n trc tung tm c nhit bu t t
= 17,5
o
C.

T A ko song song vi ng d = const cho n ng = 1, t giao im ny theo ng t =
const n trc tung tm c nhit im sng, t
s
= 16,3
o
C.

8.3. Cn bng vt liu ca qu trnh sy
8.3.1. Mi lin kt m
m c ht vo trong vt liu v to thnh mi lin kt ca cc trng khc nhau. Da vo bn
cht ca lc lin kt ngi ta xp thnh ba nhm lin kt chnh: lin kt ho hc, lin kt ho l v lin
kt c l.
a) Lin kt ho hc
Th hin di dng lin kt ion hay lin kt phn t. Lng m trong lin kt ho hc chim mt t
l nht nh. Vt liu khi b tch m lin kt ho hc th tnh cht ca n thay i. Ni chung trong qu
trnh sy (120 150
o
C) khng tch c m lin kt ho hc.

b) Lin kt ho l
Th hin di dng lin kt hp ph v lin kt thm thu, lng m trong lin kt ho l khng
theo t l nht nh no. Lin kt hp ph c trng bi s ht m ca vt km theo qu trnh to nhit,
v li th tch vt m nh hn tng th tch ca vt kh v th tch ca m hp ph.
Lng m thm thu hp thu trong vt th gp nhiu ln lng m hp ph. c bit khi vt thu m
thm thu khng km theo s to nhit, tnh cht nc trong lin kt thm thu khng khc nc t do.
c) Lin kt c l
m lin kt c l gm cc dng: lin kt cu trc, lin kt mao dn v lin kt thm t, lng m
lin kt c l khng th hin mt t l nht nh no c.
Nh vy trong qu trnh sy tch ton b m lin kt c l, m lin kt thm thu, v mt phn m
lin kt hp ph a phn t. Phn m trong vt liu tch c khi sy gi l m t do.
8.3.2. Phng trnh cn bng vt liu chung
Trong k thut sy, ngi ta nu ln hai khi nim v m vt liu:
m vt liu tnh bng phn trm khi lng ca vt liu t. V d: ngi ta gi m ca vt
liu l 10% khi lng ca vt liu t, tc l nu vt liu t l 100kg th lng m cha trong vt liu
l 10kg, v lng vt liu kh tuyt i l 90kg.
m vt liu tnh theo phn trm khi lng vt liu kh tuyt i. V d: nu ta c m ca
vt liu l 10% khi lng vt liu kh tuyt i tc l lng vt liu t l 110kg, lng m trong l
10kg v lng vt liu kh tuyt i l 100kg.
Ta t mt s k hiu:
G
a
Khi lng nc cha trong vt liu, kg.

G
0
Khi lng vt liu kh tuyt i, kg.

G Khi lng vt liu m, kg.
w m vt liu so vi khi lng vt liu m, %.
W m vt liu so vi khi lng vt liu kh tuyt i, %.
U Hm m, kg/kg.

T hai khi nim v m trn, ta c th tnh ton chuyn t m ny sang m kia theo cng
thc sau:

8.3.3. Trng thi cn bng nhit m ca vt liu
Vt liu m t trong mi trng khng kh m s xy ra qu trnh trao i nhit m cho n khi t
trng thi cn bng nhit ng lc. Trng thi cn bng c lin quan cht ch n cc mi lin kt m
trong vt liu.
Trong trng thi cn bng phn t, nhit ca vt liu bng nhit ca mi trng khng kh
xung quanh, cn p sut ca hi nc trong vt liu bng p sut hi nc ring phn trong khng kh.
Hm m ca vt liu t gi tr khng i c gi l hm m cn bng hoc m cn bng.
Nh vy m cn bng ca vt liu ph thuc vo nhit v m ca mi trng xung quanh,
ng thi ph thuc vo phng thc t n trng thi cn bng , vt liu c th t n trng thi
cn bng do thi m (sy). ng biu din m cn bng ca vt liu ph thuc vo m ca khng
kh trong iu kin nhit khng i gi l ng ng nhit. Nu vt thi m t trng thi cn bng
th gi l ng ng nhit thi m.

Hnh 8.3. Hm lng m cn bng ca tinh bt ng v tinh bt bin tnh
O Tinh bt ng; Tinh bt bin tnh
Thc nghim chng minh rng, trong trng thi cn bng hm m ca vt liu phn b u theo
th tch, lc hm m mi im ca vt liu c gi tr nh nhau v gi l hm m trung bnh.
8.4. ng hc ca qu trnh sy
8.4.1. Khi nim chung v din tin qu trnh sy
ng hc nhm nghin cu s bin i hm m ( m) v nhit trung bnh ca vt liu theo thi
gian sy, tc l tm hai hm ny c xc nh bi tnh cht ho l ca vt liu. Trng
hm m v trng nhit c xc nh bi cc quy lut ca truyn vn m v nhit bn trong vt liu,
cng nh s trao i nhit m vi mi trng xung quanh.
S bin i nhit v hm m trung bnh ca vt liu theo thi gian, trc ht c xc nh bi
cc quy lut tc dng tng h gia vt liu vi mi trng xung quanh, tc l s trao i nhit m vi
mi trng bn ngoi.
8.4.2. ng cong sy
Trc ht, cn nm c cc quy lut cn bn ca qu trnh sy vt liu m. Trong qu trnh sy, vt
liu nhn nhit t bn ngoi v thi m ra mi trng xung quanh.
S ph thuc (trn th) gia hm m ca vt liu v thi gian sy c gi l ng cong sy
(hnh 8.4). tm c s ph thuc ny, em vt liu m sy i lu n gin bng khng kh nng
(xem nhit khng kh t
k
, m khng kh
k
v tc v
k
khng i) v gi s hm m phn b u
trong vt liu (lp vt liu mng). Phn tch ng cong sy v nhn thy din bin ca qu trnh nh
sau (hnh 8.4):

Hnh 8.4. S bin i m v nhit ca vt liu theo thi gian sy
Giai on t nng vt liu:
Nu ban u nhit ca vt liu thp hn nhit bay hi on nhit ca khng kh, th trong giai
on t nng, nhit ca vt liu tng ln. Trong giai on ny hm m vt liu thay i rt chm v
thi gian din tin nhanh.
Giai on sy ng tc:
Sau giai on t nng, hm m ca vt liu gim tuyn tnh theo thi gian sy (on thng trn
ng cong sy). Nu gi s gim hm m ca vt liu trong mt n v thi gian l tc sy (tc l
l tc sy) th trong giai on ny nn c gi l giai on ng tc, giai on sy
ng tc ko di n thi im m hm m ca vt liu t n gi tr w
k
no (w
k
gi l m ti
hn ca vt liu).
Giai on sy gim tc:
Khi m ca vt liu t n mt gi tr gii hn w
k
th tc sy bt u gim dn, v ng
cong sy chuyn t ng thng sang ng cong tim cn dn n m ca vt liu trong iu kin
ca qu trnh sy. Khi m ca vt liu t gi tr m cn bng, hm m ca vt liu khng gim
na v tc sy = 0, qu trnh sy kt thc.
Nh vy thi gian sy vt liu bng tng thi gian ca ba giai on ni trn.
=
0
+
1
+
2

0
thi gian t nng vt liu.

1
thi gian sy ng tc.

2
thi gian sy gim tc.

8.4.3. S thay i nhit ca vt liu trong qu trnh sy
Khi sy, vt liu nhn nhit lng t bn ngoi, trc ht lng nhit c hp thu trn b mt vt
liu, sau bng dn nhit truyn vo bn trong vt liu. V l nhit b mt tng sm hn nhit
tm vt liu (hnh 8.4). Trong giai on t nng, nhit vt liu tng t nhit ban u
0
cho n
nhit
1
tng ng vi nhit bay hi on nhit ca khng kh mi trng xung quanh. Sut giai
on sy ng tc, nhit vt liu khng thay i v vn gi gi tr
1
. iu c ngha l trong giai
on sy ng tc ch yu tch m t do, v p sut hi m trong vt liu bng p sut hi bo ho trn
b mt thong ( = 1), cn nhit b mt vt liu bng nhit bu t (
1
=
m
= t
). Nhit tm
vt liu
x
t nhit bu t chm hn mt cht. Nh vy trong giai on sy ng tc, nhit b
mt v nhit tm vt liu c gi tr nh nhau (
m
=
x
= t
), nn gradien nhit trong vt liu

bng khng:
Ghi ch: S bay hi on nhit:
nc bay hi vo mi trng xunh quanh, khng kh ng vai tr l phng tin vn chuyn.
Khng kh mang nhit cung cp cho b mt bay hi ca nc v nhn lng hi nc em i. Qu trnh
trao i nhit m xy ra trong iu kin on nhit m hm m ca khng kh tng ln, cn nhit
gim i.
Khi chuyn sang giai on sy gim tc, nhit b mt vt liu tng theo thi gian cui qu trnh
sy (lc w = w
0
), nhit t gi tr nhit mi trng t
k
. Nhit tm vt liu cng tng theo thi
gian, song chm hn, do vy trong vt liu xut hin gradien nhit . Gradien nhit ny
gim dn n lc m vt liu t n trng thi cn bng th bng khng (lc
m
=
t
= t
k
).

8.4.4. Tc sy
8.4.4.1. Cc yu t nh hng n tc sy
Tc sy ph thuc vo nhiu yu t, ch yu l:
Bn cht vt liu sy: Cu trc, thnh phn ho hc, c tnh lin kt m v.v
Hnh dng vt liu: Kch thc mu sy, chiu dy lp vt liu sy v.v Trong trng hp cc
iu kin khc khng i ta c th xem nh tc sy t l vi t s gia b mt ca cc phn t vt
liu sy vi th tch ca n, b mt ca vt liu sy cng ln th qu trnh sy tin hnh cng nhanh.
m ban u v ban cui ca vt liu sy, ng thi c m ti hn ca vt liu.
m khng kh, nhit v tc ca khng kh. Nhit khng kh cng cao, tc khng
kh cng ln, m tng i ca khng kh cng nh th qu trnh sy tin hnh cng nhanh. Nhng
nhit khng kh khng th vt qu nhit sy cho php ca tng loi vt liu, c th tc ca tc
nhn sy (khng kh) cng khng th qu ln v cn ph thuc vo iu kin lm vic v ch sy.
Tc nhn sy: C th sy bng khng kh hoc bng khi l, nu bng khi l th nhit cao,
nhng cng ch s dng c vi mt s vt liu chu c nhit cao.
Chnh lch nhit ban u v nhit cui ca tc nhn sy, nhit cui gim t th nhit
trong bnh ca tc nhn sy cng cao, do tc sy cng tng. nhng khng nn chn nhit cui
qu cao v khng s dng trit nhit.
Cu to mng sy, phng thc sy v ch sy.
Trn y nu ln mt s yu t c bn c nh hng trc tip n tc sy v thi gian sy, ta cn
bit cc yu t khi tin hnh sy mt vt liu c th th c th chn c nhng iu kin sy
thch hp nht.
8.4.4.2. ng cong tc sy
Nh trn ni, khi sy lng m bc hi gim dn theo thi gian v do tc sy cng bin i
theo thi gian, tc l bin i theo m ca vt liu. Vy khi nghin cu v sy ta nn tm hiu quan
h gia m ca vt liu vi thi gian sy v quan h gia tc sy vi m ca vt liu. i vi
tng vt liu sy c th, ta c th ly nhng s liu thc nghim v t v c ng biu din cc
mi quan h trn. ng biu din mi quan h gia m W ca vt liu vi thi gian sy gi l
ng cong sy (hnh 8.5). ng biu din quan h gia tc sy v m W ca vt liu gi l
ng cong tc sy (hnh 8.6).
Ta nhn xt qua hai biu :

Hnh 8.5. ng cong sy Hnh 8.6. ng cong tc sy
on AB: giai on t nng vt liu, nhit vt liu tng ln n nhit bu t, tng ng
vi trng thi khng kh lc sy, m vt liu thay i khng ng k, tc sy tng nhanh n
tc cc i.
on BK: Giai on tc sy khng i (ng tc) m vt liu gim nhanh v u n theo
mt ng thng (on BK trn ng cong sy), nhit vt liu khng i v vn bng nhit bu
t.
on KC: Giai on tc sy gim dn nhng u (ng chm l ng l thuyt), nhit
ca vt liu tng ln dn, m gim dn n m cn bng nhng mc gim chm hn giai on
trn. im C tng ng vi m cn bng, khi t m cn bng th nhit ca vt liu bng nhit
ca tc nhn sy.
Qua cc nhn xt trn ta c th kt lun l qu trnh sy mt vt liu t n m cn bng gm
hai giai on chnh:
1. Giai on tc sy khng i cn gi l giai on ng tc: lc ny vt liu cn nhiu nc, tc
khuch tn ca nc bn trong vt liu ln hn tc bay hi trn b mt vt liu, v th tc sy
trong giai on ny khng ph thuc vo cc yu t bn trong ca vt liu (v d chiu dy vt liu,
m ban u ca vt liu) m ch ph thuc vo cc yu t bn ngoi (v d: nhit , tc v m
ca khng kh sy v.v) khi cc yu t bn ngoi khng i th tc sy cng khng i.
Vy mun tng tc sy th ch yu thay i cc yu t bn ngoi. Ta c th tng nhit sy cao
hn nhit cho php ca vt liu v b mt vt liu cn ang t nn nhit vt liu xp x bng
nhit bu t t
, nhng cn ch l chn nhit sy th no nhit bu t t
phi nh hn
nhit cho php ca vt liu.
2. Giai on tc sy gim dn
Lc ny vt liu tng i kh, lng nc trong vt liu cn t nn tc khuch tn ca nc
trong vt liu gim xung nh hn tc bay hi ca nc trn b mt vt liu. Do tc sy trong
giai on ny ch yu ph thuc vo tc khuch tn ca nc bn trong vt liu, lng m khuch
tn gim dn nn lng m bay hi cng gim, do tc sy cng gim. V vy, tc sy khng
phi ph thuc cc yu t bn ngoai vt liu m ph thuc ch yu vo cc yu t bn trong ca vt liu,
cho nn mun tng tc sy giai on gim tc ta phi khc phc tr lc khuch tn bn trong vt
liu. Nh ni trn, nhit ca vt liu sy lc ny bt u tng dn v cho n khi t c m
cn bng th nhit ca vt liu bng nhit ca tc nhn sy, v vy n giai on ny ta phi gi
nhit cho php ca vt liu.
Vic xc nh hai giai on sy c ngha quan trng v t ta c th thit lp ch sy khc
nhau, thch ng vi c im ca tng giai on c th va m bo cht lng ca sn phm, ng
thi tit kim nng lng rt ngn c thi gian sy.
8.5. Phn loi qu trnh sy v thit b sy
Mc tiu ca qu trnh sy l lm sao thu c cc vt liu kh m cht lng ca n vn m bo
trong iu kin chi ph t nht.
C s l thuyt trnh by trn y cho thy qu trnh sy th hin hai giai on r rt:
Giai on sy ng tc ph thuc ch yu vo cc yu t bn ngoi (s trao i nhit m vi mi
trng).
Giai on sy gim tc ph thuc vo cc c tnh bn trong (s chuyn vt nhit m trong lng vt
liu).
Vt liu em sy c th nhiu trng thi khc nhau. Do vy cn t chc qu trnh sy cho ph hp.
Ngi ta thng phn loi qu trnh sy nh sau:
Sy lp vt liu trong trng thi tnh (bung sy).
Sy lp vt liu tnh c chuyn ng tng i (sy bng ti).
Sy lp vt liu trong trng thi xo trn (thng quay).
Sy vt liu trong trng thi l lng (tng si).
Sy vt liu trong trng thi phn tn (sy phun).
Theo cc phng php cng ngh ny, ngi ta ch to cc dng thit b sy khc nhau v c
phn loi nh sau:
Phn loi theo ch lm vic: Thit b sy gin on, thit b sy bn lin tc v thit b sy lin
tc.
Phn loi theo p sut lm vic trong bung sy: Thit b sy p sut cao, thit b sy p sut kh
quyn (p sut thng), thit b sy p sut thp (sy chn khng) v thit b sy p sut rt thp (p sut
t trng thi im ba ca nc) gi l sy ng kh.
Phn loi theo kt cu thit b:
Phng sy, t sy, hm sy.
Thp sy, thng sy quay.
Sy bng ti, sy a.
Sy tng si.
Sy kh ng.
Sy phun.
V phng din kt cu, thit b sy rt a dng v phong ph v chng loi. Cc thit b sy hin
i c kt cu gn nh, hnh thc p, trnh c gii ho v t ng ho cao. Tuy nhin v nguyn tc
t chc qu trnh sy vn theo cc cch nu trn. Trong phn sau chng ta cp n ba dng thit b
sy ch yu v thng dng trong ngnh dc.
8.5.1. Thit b sy i lu
Cc thit b sy thng dng thng gp l: T sy, phng sy, hm sy. Trong cc thit b sy ny c
th p dng sy i lu cng bc hoc i lu t nhin, cng c th p sut thng hoc p sut
chn khng. T kch thc nh thng c s dng trong cc phng th nghim, cu to tng i n
gin v d vn hnh.

Hnh 8.7. Nguyn tc cu to phng sy Hnh 8.8. T sy Glatt
Cu to phng sy c m t trn hnh 8.7. V bung sy 1 c bc cch nhit, bn trong b tr
nhiu ngn, ti mi ngn b tr nhiu gi khay 9, c th to trong bung sy cc rnh dn tc nhn 3.
Phng sy l loi thit b lm vic gin on, vt liu thng cha trong cc khay vi chiu dy thch
hp. Nhp liu vo v ly liu ra thc hin theo chu k bng cch m ca phng sy. Tc nhn sy l
khng kh qua ca 4, ri vo caloriphe si 5 nng n nhit sy. S chuyn ng ca khng kh
nh nng lng c cung cp bi qut ly tm 6 vo rnh 3 di chuyn theo cc nh hng 2 qua li
phn phi 8 thi song song dc theo cc b mt cc khay cha vt liu. gim chiu di phng sy,
ngi ta b tr o chiu chuyn ng ca khng kh nng bng cc hng dng 2 ng thi b tr
caloriphe ph 7 t khng kh gia chng nhm phc hi kh nng sy ca tc nhn. Khng kh sau
sy cng c thi qua ca 4. Ca 4 c cu to nh van bn ng lm nhim v iu chnh h s tun
hon kh thi.
Phng sy l thit b n gin v c s dng rt ph bin. T cu to trn hnh, c th thay i
cht t chuyn sy thi tc nhn song song sang sy thi tc nhn vung gc.
Trong phng sy hin i, ngi ta b tr b phn iu khin v iu chnh t ng, nhm m bo
chun xc cc thng s v ch sy, mc d c s tc ng ca cc yu t bn ngoi.
8.5.2. Sy vt liu trong trng thi tng si
8.5.2.1. c tnh thy ng lc ca tng l lng
Lp vt liu dng ht trong trng thi tnh c chiu cao h
o
tng ng vi xp
0
. Khi thi dng
kh vung gc vi b mt lp ht vi vn tc v
k
th p sut tnh ca dng kh b gim i mt i
lng p v c gi l tr lc ca lp ht.
Giai on u khi tc dng kh v
k
cn b, nu tng tc th tr lc tng nhng trng thi lp ht
vn khng thay i. Trn hnh 8.9, biu din s ph thuc gia tr lc p v tc dng kh. Khi tc
t n gi tr nht nh th tr lc t cc i (im k
1
) cc ht vt liu bt u linh ng v lp ht vt
liu th hin tnh nht ca cht lng. im k
1
tng ng vi trng thi ti hn, tc tc dng kh gii
hn chuyn lp vt liu tnh vo trng thi gi lng. Qua im k
1
tip tc tng tc dng kh th
gim p khng thay i bao nhiu nhng th tch lp vt liu tng ln nhiu. Tc dng kh tng n
im k
4
th cc ht vt liu b li cun theo dng kh, tc khi ht chuyn vo trng thi vn chuyn kh
ng. Tc dng kh tng ng vi im k
4
gi l tc pht. Trng thi vt liu t k
1
n k
4
c
gi l trng thi gi lng. S truyn nhit v truyn m gia dng kh nng v vt liu trong trng
thi gi lng rt mnh lit nn c ng dng trong k thut sy vt liu (hnh 8.9).
8.5.2.2. K thut sy tng si
Trong k thut sy, ngi ta chia trng thi gi lng ca vt liu ra ba giai on: t k
1
n k
2
l
trng thi tng si, t k
2
n k
3
l trng thi l lng, t k
3
n k
4
l trng thi pht.

Hnh 8.9. S bin i chiu cao v tr lc ca lp ht vt liu theo tc ca dng kh
Ba giai on chnh hnh thnh lp gi lng trn mt li phn phi c biu din thng qua tc
ch o ca dng kh qua l li phn phi nh sau:

Trong : + v
ak
tc ch o ca dng kh (m/s).

+ v
k
lu lng ca kh (m
3
/s).

+ F
d
din tch tit din cc l trn mt li: (m
2
).

Qua thc nghim nhn thy:
Trng thi tng si: v
ak
2v
cmax

Trng thi l lng: v
ak
= 2 3v
cmax

Trng thi pht: v
ak
v
cmax

v
cmax
tc cn bng ca ht vt liu (m/s).

Trong k thut sy tng si, i hi phi to c lp tng si ng nht v n nh. Thc t sn
xut cho thy lp l lng ng nht hn lp tng si. xp ca lp tng si 0,75 tng ng vi
chiu cao lp vt liu tng 2 3 ln. Thc t cng cho thy m ca vt liu c nh hng ln n tc
ti hn.
Trong qu trnh sy, thng nhit trn b mt li phn phi cao hn nhit trong bung sy.
Thnh phn c ht cng nh hng n ch chuyn khi vt liu vo trng thi tng si. i vi
khi ht a phn tn th s gin n ban u im ti hn vo lp tng si phi ln hn (1,25 1,4) ln.
i vi li phn phi, kch thc l hoc khe h phi c chn sao cho ht vt liu khng lt.
Li phn phi ng vai tr quan trng trong thit b sy tng si, khng nhng c nhim v khi ht
m cn gp phn to s chy ri v phn b ng u tc nhn sy l khng kh nng theo tit din
bung sy, ng thi hnh thnh v s cc dng tia m cc ht vt liu c treo trng thi l lng.
S trao i nhit m trong tng l lng ph thuc vo tnh cht vt liu v ch sy. Trn hnh
8.10 v hnh 8.11 m t s v my sy tng si.
So snh hai loi thit b sy:
T sy i lu, nhit phi thm nhp v hi phi khuch tn qua mt ng dn di.
T sy tng si: Cc ht nh c bao quanh bng khng kh nn nhit phi thm nhp v hi
khuch tn qua mt ng dn nh bng bn knh ca ht nn qu trnh sy nhanh din ra hn.
Nhit phn b trong sy tng si thp. Sn phm dng sy kh chu mt iu kin nhit ging nhau
nn kt qu sy ng nht.
Trong t sy tng si, vt liu tip xc khng kh sy bao quanh nhit rt thp trong khong thi
gian ngn nn c t s thay i nhng tnh cht l ho ca sn phm, l mt h thng sy thch hp cho
nhng sn phm nhy cm vi nhit. S khuch tn mu, trng hp chai ho v caramen ho trnh
c. y l mt s li ch ln ca tng si.

Hnh 8.10. S my sy tng si Hnh 8.11. My sy tng si Glatt
Tit kim lao ng: t sy khay tn cng ri vt liu sy ra cc khay. Sy tng si ton b vt liu
t trong mt thng chnh, tit kim thi gian v lao ng trong np liu v lm sch.
T sy tng si chim din tch sn bng 1/3 so vi t sy c in v cng mt thi gian cho nng
sut cao gp ba ln.
8.5.3. Sy phun
Sy phun dng sy cc dung dch v huyn ph trong trng thi phn tn. Thit b sy phun c
kt cu tng i phc tp, trong qu trnh sy xy ra rt mnh lit. S trao i nhit m xy ra ngay
trong lng th tch cc git cht lng. Ngha l qu trnh sy thc hin i vi tng git cht lng phun
ra. Do vy sn phm ca sy phun l mt dng bt mn.
T cc cng trnh nghin cu v sy phun ngi ta rt ra cc c im ch yu sau:
Trong giai on sy ng tc, p sut hi m ti b mt bay hi ca git lng xp x p sut hi
bo ho, cn nhit tng ng vi nhit bu t.
Tc bay hi t gi tr cc i, qu trnh ch gii hn bi cc yu t trao i bn ngoi (ch
sy).
Thy ng lc ca s phun ng vai tr to ln trong thit b sy phun.
Qu trnh xy ra ch yu trong giai on ng tc.
m ti hn trung bnh ca cc git lng thng ln hn ht m cc i.
Giai on sy gim tc l giai on hnh thnh cc ht rn.
T dung dch hoc huyn ph phi phn tn thnh cc git lng li ti trong thp sy. Thc hin cng
vic ny nh c cu c bit gi l vi phun. i vi mi vi phun th hin ng knh chm phun, s
phn b mt cc git lng theo bn knh phun v kch thc ca git lng.
Ngi ta thng dng cc loi vi phun sau: vi phun c kh (vi phun thy lc), vi phun kh
ng, vi phun ly tm (vi phun a) (hnh 8.12).
Mun xc nh c vi phun thch hp cn bit:
Tnh cht ho l ca dch phun.
Tnh cht mi trng kh xung quanh.
gim p sut ca vi phun.
Dng vi phun v lu lng dch phun.
Trn hnh 8.13 trnh by nguyn l cu to ca thit b sy phun dng khng kh nng. Khng kh
(4) nh qut thi (5) a qua caloriphe(6) nng n nhit sy. Dung dch sy (1) nh h thng
bm cao p a vo vi phun (2) t trn nh thp sy, di tc dng ca p sut cao. Dung dch c
phn tn thnh cc git lng li ti. Chm tia phun c dng tc nhn nng (8) phn tn u khp th tch
thp, ri cng chuyn ng xung y thp. Sn phm kh c tch t ti y v nh b tho liu a
ra ngoi (10), cn khng kh m theo ng ng vo xyclon tch bi (11). Sau cng kh thi nh qut
(12) tng ra ngoi cn bi sn phm ly ra t ca.
Trong thp sy phun c th t chc sy cng chiu, sy ngc chiu, vi phun c th t pha trn,
pha di hoc bn hng. m bo cho qu trnh sy (nu c th) ngi ta b tr h thng lm lnh
thnh thit b nhm chng dnh v chng chy sn phm. Trong nhiu trng hp, ngi ta b tr h
thng rung ng trn thnh thp sy nhm tch sn phm kh dnh trn .

CU HI LNG GI
Chn cu tr li sai
1. ng lc ca qu trnh sy phi l:
a) Gradient nhit ;
b) Gradient hm m;
c) Gradient p sut hi m;
d) S ng p ti b mt bc hi ca vt liu.
2. Sy l qu trnh:
a) t nng vt liu;
b) Lm kh vt liu;
c) Tch m bng nhit;
d) b v c ng.
3. C ch ca qu trnh sy bao gm cc qu trnh:
a) Cp nhit cho b mt vt liu;
b) m di chuyn ra b mt vt liu;
c) Nung nng vt liu;

Hnh 8.12. Cc loi vi phun
a, b, c Vi phun thu lc;
d, e Vi phun kh ng; f a phun.

Hnh 8.13. S my sy phun
d) Dn nhit t b mt vo bn trong vt liu.
Chn cu tr li ng
4. ng lc ca qu trnh bay hi l:
a) Nhit kh ca tc nhn sy;
b) Nhit t ca khng kh;
c) Nhit im sng;
d) Th sy t
k
.

5. Hin tng ngng t nc trong phng sn xut l do:
a) Nhit phng qu lnh;
b) m trong phng qu cao;
c) Khng kh m trong phng trng thi qu bo ho;
d) Khng cu no ng.
6. m tng i ca khng kh l:
a) Lng hi nc cha trong mt m
3
khng kh m;

b) T s gia m tuyt i v bo ho ca khng kh m;
c) T s gia m tuyt i v lng hi nc bo ho ca trng thi khng kh cng p sut v
nhit ;
d) a v b ng.
7. Hm m ca khng kh l:
a) Lng hi nc cha trong 1kg khng kh m;
b) Lng hi nc cha trong 1kg khng kh;
c) Lng hi nc cha trong 1kg khng kh kh;
d) Lng hi nc cha trong 1kg khng kh kh tuyt i.
8. S dng gin khng kh m, c th xc nh:
a) Hm m ca khng kh;
b) Nhit kh, nhit t ca khng kh;
c) Entanpy ca khng kh trng thi ;
d) Cc thng s trng thi ca khng kh m iu kin th nghim.
9. K thut sy i lu khng tch c m trong vt liu trng thi:
a) Lin kt ho hc;
b) Lin kt ho l;
c) Lin kt c l;
d) Lin kt mao dn.
10. Khi xc nh m cn li ca cm trong qu trnh sn xut vin nn ta dng cch tnh:
a) m vt liu tnh theo phn trm khi lng ca vt liu t;
b) m vt liu tnh theo phn trm khi lng ca vt liu kh tuyt i;
c) m vt liu tnh theo hm m tng i;
d) C th dng c hai cch tnh a v b.
11. tng cng qu trnh sy trong iu kin ng p mt nhit nht nh ta c th:
a) Tng cng lu lng tc nhn sy;
b) Gim m ca tc nhn sy i vo;
c) C th s dng a v b;
d) Khng th s dng ng thi a v b.
12. T sy ht t trong quy trnh sn xut vin nn lm vic theo nguyn l:
a) Bc x nhit;
b) Sy i lu;
c) Sy thng hoa;
d) Sy tng si.
13. m cn bng ca vt liu sau khi sy ph thuc:
a) Nhit mi trng xung quanh;
b) m tng i ca mi trng xung quanh;
c) Ch ph thuc vo bn cht vt liu;
d) C a v b.
14. Trong cng ngh sy i lu, hiu qu sy ph thuc vo:
a) Thi gian t nng vt liu;
b) Thi gian say ng tc;
c) Thi gian sy gim tc;
d) Thi gian vt liu sy t n m cn bng.
15. C th iu khin tc qu trnh sy giai on:
a) t nng vt liu;
b) Sy ng tc;
c) Sy gim tc;
d) Tng nhit tc nhn sy i vo.
16. Trong giai on sy ng tc, tc sy ph thuc vo:
a) Chiu dy ca lp vt liu;
b) m ban u ca vt liu;
c) Nhit , m, tc ca tc nhn sy i vo;
d) p sut hi ca khng kh thi vo.
17. Thit b no c th thc hin quy trnh sy i lu lin tc:
a) T sy;
b) Bung sy;
c) Phng sy;
d) Sy bng ti;
e) Cc thit b sy a, b, c.
18. Trong phng sy i lu c th tng hiu qu kinh t bng cch:
a) Tun hon 100% tc nhn sy;
b) Tun hon mt phn kh thi;
c) S dng ton b tc nhn sy mi;
d) Chuyn chiu thi ca tc nhn sy t song song sang vung gc vi b mt vt liu sy.
19. Trong thit b sy tng si, trng thi sy ti u nht l:
a) Trng thi gi lng;
b) Trng thi tng si;
c) Trng thi l lng;
d) Trng thi pht.
20. Cng ngh sy phun ng dng:
a) Sy ht t;
b) Sy dch chit dc liu;
c) Sy bao phim;
d) Sy bt mn.
21. Trong k thut sy phun, vic la chn vi phun khng cn tnh n:
a) nht ca dung dch;
b) Lu lng phun (kg/gi);
c) Bn cht ho hc ca dch phun;
d) Nguyn l cu to thit b sy.
22. Nhit ca vt liu sy ch t mc ti hn bng nhit tc nhn sy giai on:
a) t nng vt liu;
b) Sy ng tc;
c) Sy gim tc;
d) Ti mi thi im ca qu trnh sy.
23. Nhit b mt vt liu sy khng thay i v bng nhit bu t khi chu trnh sy ang trong
giai on:
a) t nng vt liu;
b) Sy ng tc;
c) Sy gim tc;
d) mi im trn ng cong sy.
24. Tc sy bin i theo:
a) Thi gian sy;
b) S bin i hm m trong vt liu;
c) Trng thi lin kt m trong vt liu;
d) C a v b.
25. Mt quy trnh sy ti u ph thuc:
a) Loi thit b sy c chn;
b) Mc hin i ca thit b sy;
c) Thm nh cc yu t cng ngh ca qu trnh sy;
d) n nh cc thng s cng ngh ca quy trnh sy.
26. Trong qu trnh sy mt vt liu, yu t no kh n nh nht:
a) Bn cht vt liu;
b) m ban u v m cui cn li trong vt liu;
c) m ca tc nhn sy;
d) Lu lng ca tc nhn sy.
27. ng lc ca qu trnh bay hi l:
a) Nhit kh ca tc nhn sy;
b) Nhit t ca khng kh;
c) Nhit im sng;
d) Th sy t
k
.

TI LIU THAM KHO
1. KACATKIN, Nhng qu trnh v thit b c bn ca ngnh cng ngh ho hc, tp 3, NXB Gio
dc H Ni, 1996.
3. Michael E.Aulton, Pharmaceutics: The Science of Dosage Form Design.
4. Nguyn Vn La, K thut sy vt liu, tp 7, Trng i hc Bch khoa TP. H Ch Minh.
5. S tay qu trnh v thit b cng ngh ho cht, tp 2, NXB Khoa hc v k thut H Ni, 1978.

Bi 9
QU TRNH NN DP VT LIU
MC TIU
1. Phn tch c vai tr cc thng s ca ht vt liu.

9.1. Khi nim chung
Cc khi nim v nn dp: Ba khi nim chnh.
+ Nn p bt (compaction of powders). Thut ng chung trong m t trng thi vt liu phi chu
tc ng ca cc lc c hc. Trong cng nghip dc, hiu qu ca lc nn p l c bit quan trng sn
xut vin nn, vin nang cng, cm ht v x l bt ni chung.
+ Nn dp (compression) c ngha l lm gim th tch khi ca vt liu do kt qu th ch ca pha
kh bng pha rn.
+ Lm chc ht (consolidation) lm tng bn c hc ca vt liu do kt qu tng tc gia cc
ht.
Vt liu trong qu trnh nn dp
Khng ging cc trng thi vt l khc ca vt cht, cc cht rn dng bt l mt hn hp khng
ng nht bao gm nhng ht ring r c hnh dng v kch c khc nhau rt rng, chng c phn b
ngu nhin vi nhng khong trng khng kh xen k gia chng. V l do ny, gn nh khng c kh
nng biu th c im ca h thng ny mt cch y bng nhng ngn ng c trng c bn. Tuy
nhin, nhng cng trnh nghin cu kt hp hai trng thi: Ht c th v ht khi bt, a ra nhng
yu t quan trng, ng dng hu ch trong ngnh cng nghip dc.
9.1.1. B mt phn cch rn kh
Cc nguyn t hay ion nh v trn b mt mt ht rn bc l ra s phn b khc nhau cc lc lin
kt ni phn t v ngoi phn t trong ht (hnh 1). Chng phi ng u vi nhng lc ht phn t
khng bo ho hng ra ngoi khong cch nh pha bn ngoi b mt ht rn. iu kin ny lm tng
ln nng lng b mt t do ca ht. Nng lng ny gi vai tr chnh trong tng tc gia cc ht v
gia ht vi mi trng xung quanh. Nhiu hin tng quan trng nh: hp th, dnh kt, bm dnh, tc
ho tan v kt tinh biu th tnh cht c bn ny ca tt c cc cht rn.

2. Trnh by c cc khi nim v hiu ng lc ng dng.
3. Trnh by c nguyn l to ht t v nh hng ca tnh cht ht n qu trnh nn dp.
4. Trnh by c s thit b nghin cu qu trnh nn dp.
Hnh 9.1. S phn b cc lin kt ht gia cc phn t, ion hoc nguyn t
trong mt vt rn so vi b mt ca n
Do nhng lc lin kt khng bo ho b mt hat, khi cc ht tip xc vi nhau, cc tiu phn ht
nhau cht lm chng dnh li vi nhau (vn cc). S ht nhau gia cc ht vi nhau th ny gi l s
c kt (cohesion). Khi cc ht tip xc vi mt ht rn khc hoc b mt khc chng b hut dnh li vi
nhau gi l hin tng bm dnh (adhesion).
Hin tng ny c nh hng trn mt vi cng on thao tc: S chy ht t phu hay thit b cp
liu, chuyn ng tng i trong my trn hay my dp trong sn xut ht v vin nn.
Ton b s n nh i vi chuyn ng tng i ca cc ht c th b nh hng bi hai yu t
khc. Th nht: Nhiu loi bt dc phm c s tch tnh in, c bit khi phi chu ma st bn trong.
Th hai: S c mt ca lp m hp th trn ht lm gim nh hng ca tnh in. Tuy nhin, mng m
ny c th hnh thnh cu m gi cc ht li vi nhau bi hiu qu ca sc cng b mt v p lc mao
dn.
9.1.2. Gc ngh (hnh 9.2)
Gc ngh ca bt xc nh theo cng thc:

9.1.3. Tc chy
y l gc ngh ti a c th thu c, n gip ta
nh gi nh hng ca lc c kt bn trong v kt qu
ma st bn ngoi ca cc ht.
Khi tin hnh o cn thn, kt qu o gc ngh ng
c th dao ng vi lch chun tng i khong 2%.
Trn thc t, chng rt nhy cm vi s thay i trong
phn b c ht, vi hm m ca ht. o gc ngh gip
cho ngi sn xut mt phng php nhanh chng
quan st s khc nhau quan trng gia l ny v l khc
khi kim tra trong sn xut.

Hnh 9.2. o gc ngh ca khi bt hnh nn
o tc chy Q ca bt qua mt my o tc chy
hoc mt l trn (v d: mt ci dp vin) gn trn mt ci
gi, th nghim o chy vi nhng hn hp ht c kch c
khc nhau ca cng mt loi vt liu, sau xc nh c
mt t l phn b ht ti u nu c chy ti a. Khi t l
bt mn trong hn hp vt qu khong 40% s c hin
tng tc chy gim t ngt.
nh gi tc chy ca ht, mt cch n gin
ngi ta p dng khi nim ch s nn (I) tnh theo cng
thc:
9.1.4. Quan h th tch khi lng
Mc d khi lng ca mu bt c th c cn vi chnh xc cao, vic o th tch ca n li
cng phc tp hn nhiu. Vn chnh lm tng th tch ca khi bt l cc khong trng khng kh
trong khi bt. C th phn bit ba loi khong trng khng kh (hnh 9.4).
a) Khong trng h trong mt ht
b) Khong trng kn trong mt ht
c) Khong trng gia cc ht
Bi vy ngi ta ngh ba cch hiu v "th tch bt".
Th tch thc (V
t
true volume): L th tch ton b ca cc ht rn loi tr tt c cc khong
trng ln hn kch thc phn t v c gi tr c trng cho mi loi nguyn liu.
Th tch ht (V
g
granular volume): Th tch chim ch bi cc ht bao hm c ch trng bn
trong ht (nhng khng bao hm ch trng gia cc ht).
Th tch khi (V
b
bulk volume): Th tch chim ch ca ton b khi bt khi o.

Do s gii thch ph thuc vo phng php o. Ngoi ra ngi ta cn dng khi nim th tch
tng i (V
r
relative volume):

Trong :
+ V Th tch chim ch ca mu bt sau khi chu mt
quy trnh g chun ho.
+ V
0
Th tch ca mu bt trc khi g.

Gi tr ca I di 15% cho mt c tnh chy tt, nhng
khi ch s khong 25% kh nng chy km.

Hnh 9.3. My o tc chy ca ht
hiu ERWEKA

Trong :
V L th tch ca mu trong iu kin th nghim c th. Th tch tng i gim xung v hng
ti mt khi khong trng b loi khi khi bt. Hin tng ny xy ra trong qu trnh dp vin.
Cc ch trng hoc l trng trong cc ht to thnh mt mng mao dn tinh vi c tc dng lm tng
tc ht cht lng v lm tng tc tan r cho cc vin nn.

Hnh 9.4. Cc kiu khong trng ca ht
nh gi vai tr ca cc yu t ny ngi ta a ra mt i lng khng th nguyn th hai l
xp ca ht (E, porosity).
xp l t l th tch ton b cc ch trng (V
v
void space volume) trn th tch khi ca
nguyn liu thng c chn quan st tin trnh nn dp.

xp thng biu th bng t l %
V d: Mt vin nn trn c ng knh 10mm, dy 4mm, khi lng 480mg, t trng thc ca
nguyn liu 1,6g/cm
3
.

Th tch khi: V
b
= r
2
h

V
b
= 3,1416 x (0,5)
2
x 0,4 = 0,3142cm
3

Th tch thc: Khi lng /t trng:
9.1.5. T trng (density)
Khi nim t trng (d) l t l gia khi lng v th tch vt liu.
Tng ng vi ba loi th tch c ba loi t trng khc nhau i vi vt liu bt rn.

m khi lng ca mu th.
Khi so snh t trng (d) ca mu th trong mt iu kin th nghim c th vi t trng thc (i
khi gi l t trng l thuyt) dn n mt i lng khng th nguyn mi gi l t trng tng i (d
r
relative density).

Trong qu trnh nn dp, t trng tng i tng ti mt mc ti a l bng 1 khi tt c cc ch
trng trong ht b loi tr.
9.2. Hiu ng ca lc ng dng
9.2.1. Bin dng (deformation)

Trong nghin cu khoa hc, ngi ta thng s dng
nhng thit b hin i o th tch ca ht (nhiu x X, t
trng k helium).
Th tch khi c o bng cc cch khc nhau. n gin
nht l rt mt mu th bit khi lng vo mt ng ong
c chia vch, s dng cc k thut c chun ho: nhi, g,
rung. Cc k thut ny c s lp li nhng chnh xc khng
cao. Kt qu ph thuc nhiu vo phng php c chn.

Hnh 9.5. My o th tch v t trng
ca bt, ht hiu ERWEKA
H = H
o
H

Khi bin dng nn z c tnh theo cng thc:

T l lc nn cn thit thc hin bin dng ny trn mt din tch A c gi l ng sut
(stress):

Ghi ch: ng sut l gi tr ca ni lc pht sinh trong vt th di nh hng ca nhng tc dng
bn ngoi (ti trng, nhit v.v). n v o ng sut trong h SI l Pascan (Pa).
9.2.2. Qu trnh nn (compression)
Khi lc c hc bn ngoi tc ng ln khi bt bnh thng, c mt s gim th tch khi. l kt
qu ca mt hoc nhiu hiu ng sau: Giai on u ca s np liu thng i cng vi s sp xp li
cc ht cht hn v y l c ch chnh ca gim th tch lc ban u. Tuy nhin, s sp xp li tip theo
s kh hn v khi nn tip s c mt s loi bin dng ht xut hin:
Nu ngng nn v tin hnh x nn, qu trnh bin dng thun nghch t pht sinh nh cao su. Lc
, bin dng c gi l bin dng n hi (elastic).
Bin dng l s thay i hnh dng kch thc ca vt th
di tc dng ca mt ngoi lc (hnh 9.6).
Mt vt th rn chu tc ng bi nhng ngoi lc i nhau
s dn n s thay i c gii hn v mt hnh hc ca n. S
thay i ca vt th ph thuc vo bn cht ca lc tc ng vo
n.
Lng bin dng tng i to ra bi nhng lc nh vy l
mt i lng khng th nguyn, c gi l bin dng (strain).
Trong qu trnh nn dp c ba loi bin dng thng thng
nht (hnh 9.6):
Bin dng ko (a)
Bin dng nn (b)
Bin dng trt (c)
Nu mt thanh vt liu rn b nn bi mt lc tc ng ln
mi u (b) s gy ra s gim chiu cao (h):

Hnh 9.6. S bin dng hnh hc
ca vt th rn
Ghi ch: Bin dng n hi l bin dng bin mt sau khi b ti trng gy ra n. i vi vt rn,
bin dng n hi thng l nh v t l vi ng sut t vo n.
Qu trnh bin dng xy ra ph thuc vo thi gian nn, tc nn, tc x nn. V d: Trong
trng hp vt liu bin dng do, tc np v x ti trng qu nhanh s c th xut hin hin tng
nt gy. Ngc li khi thi gian ngng li u n di ti trng nn ko di hn, lc bin dng do
c th tip tc a n kt qu vin chc hn. Trng hp dp vin paracetamol, vt liu c xu hng
bong mt trong khi bin dng, c s nhy cm thc s vi thi gian ngng di ti trng nn ti a.
Khc phc nguyn nhn ny bng cch tc my phi chm hn, ng knh trc nn ln hn thay v
phi iu chnh cng thc vin.
9.2.3. Qu trnh lm chc vt liu (consolidation)
Khi b mt ca hai tiu phn t ti s cht ngha l phn cch t hn 50nm, nng lng b
mt t do ca chng to ra mt lc ht mnh v qu trnh c gi l hn lnh, bn cht ca lin kt mi
to thnh ging nh ca cu trc phn t bn trong ht.
c nhiu im tip xc trong khi bt v truyn lc vo khi bt di tc ng ca cc lc, cc
ht nng ln do ma st. Nu s nng ln ny khng b tiu tan th s nng ln cc b c th thch hp
V d: Khi nn aspirin, CMC, c ch nn n hi
chim u th.
Trong mt nhm bt khc, khi x nn, qu trnh phc
hi thun nghch khng xy ra ngay lp tc, khi bt vn
gi c trng thi gim th tch. Bin dng ny c gi
l bin dng do (plastic).
Ghi ch: Bin dng do l bin dng vn cn li sau
khi b ti trng tc dng ln vt th, hnh thc bin
dng do ch yu l hin tng trt gia cc phn tinh
th theo cc mt v phng nht nh gi l mt v
phng trt, do hnh thnh cc ht block, do mng tinh
th b x lch sau khi bin dng do nn bn v
cng tng ln, do v dai gim i.
Nguyn nhn ca s gim th tch khi ca vt liu
bt l mt s phi hp cc c tnh l ho ca vt liu. Tt
c cc hiu ng bin dng c th km theo s b gy v
hnh thnh lin kt mi gia cc ht lm tng chc khi
cc b mt mi c p li vi nhau.
S nn gim th tch khi bt ng vo vin nang
cng t c bng cch sp xp li v c lng bin
dng ti thiu.
Trong qu trnh nn dp vin hoc cc k thut c
bit tng t, cc trc nn c nn cao, v vy thng
ng thi xy ra s sp xp li, bin dng n hi, bin
dng do v s gy dn.

Hnh 9.7. S hiu ng ca lc nn
khi bt ln khi bt
gy nng chy b mt tip xc ca ht, lm gim bt ng sut trong vng ht . Trong trng hp
ny lin kt chy s lm tng cng c hc ca vt liu. Trong thc t c nhiu loi ho dc cha
nhit lng thp v tnh dn nhit km truyn nhit t im tip xc i l chm.
S khc nhau gia s hnh thnh lin kt kiu ny v lin kt theo kiu hn lnh c v khc nhau v
nguyn l c bn nhng kt qu cui cng l ging nhau. Trong c hai trng hp hn lnh v nng
chy qu trnh u b tc ng bi cc yu t:
Bn cht ho hc ca vt liu.
Quy m b mt kh dng.
S c mt ca cc cht lm nhim bn b mt.
Loi v mc kt tinh ca cc ht vt liu, dng tinh th, kiu kt tinh, cu trc mng tinh th
nh hng n qu trnh do s khc nhau v lin kt to thnh v lm nh hng n chc ca ht.
Mt iu ng ch hin nay, cc t dc s dng cho dp thng thng c m t nh cc tinh
th.
Nu b mt ht sch, din tch b mt ln s a n s lin kt cht ch, s nt gy trong qu trnh
nn to ra nhng b mt sch m bo cho chng gn cht hn.
y l mt yu t quan trng khi xem xt qu trnh dp vin tm ra cc nguyn nhn gy tr ngi
cho c ch ny. V d, t dc trn magie stearat l mt dng lin kt yu, nu cho vo mt lng qu
nhiu hoc trn qu k vi khi bt, s a n kt qu l qu trnh bao vin tip theo s ko di hn v
trong mt s trng hp lm cho vin mm.
Kh nng ho tan ca cht rn cng ph thuc trn p lc nn. Nu mt mng mng m hin din
trn b mt ht rn. Di p lc cao im tip xc c th p vt liu thnh dung dch, s ho tan ny
s kt tinh ho hnh thnh cu rn, cng ca n ph thuc vo tc ti kt tinh, tc chm s
to ra nhng cu trc tinh th hon thin hn vi cng cao hn.
Trong mt s trng hp khi sy cm qu kh, trong m cn li cc thp, c cht lng vin
thp hn chng minh vai tr quan trng ca m.
9.2.4. Vai tr m
Trong a s cc trng hp khi sn xut vin nn, capsul, m cn li trong cm di 1% l ti
u.
Tuy nhin theo s liu thc nghim do Shotton v Rus cng b, m cn li trong cm cc nh
(0,02%) c th nh hng n cng truyn lc xung chy di, m cn li 0,55% qu trnh
hon ton o ngc so vi vt liu kh hon ton.
Nhng nghin cu gn y chng minh phn ng dehydrat nhit ho di tc ng ca lc p,
tm ra s ph thuc trn nhit m qu trnh dehydrat ho din ra.
9.3. To ht (Granulation)
9.3.1. To ht m (moist granulation)
Thm cht lng vo khi bt c th c c trng bng mt lot cc giai on (m t bi Newitt v
Conxay Jones, hnh 9.8).
Nu cc ht bt c lm t trong giai on u (a) mng lng s hnh thnh trn b mt ht v cc
ht c th kt hp vi nhau to ra nhng cu cht lng ri rc cc im tip xc, sc cng b mt v
p sut mao dn ring trn nhng cu ni nh vy cung cp mt lc kt t v a n mt trng thi gi
l dao ng (ung a, lc lc) c cng c hc thp.
Khi lng cht lng tng ln mt s cu ni c th hp li lm tng ln mt s cu ni c th km
theo s tng cng lin kt ca cc ht m ln mc va phi (b).
Khi lng cht lng a vo nhiu hn v khi bt c nho trn mang cc ht li gn nhau
hn, cc khong trng khng kh bn trong ht c loi tr ton b, thi im ny cc cu lin kt l
kt qu ca cc lc b mt gia cc ht v p sut mao dn dn m vo cc khong trng cha cht
lng bn trong, trng thi ny gi l trng thi mao dn (c). Thm tip cht lng s to ra trng thi git
(d). Trong trng thi git, cc ht cn dnh vi nhau bi sc cng b mt nhng khng c lc ni ht,
cu trc nh vy l yu. Trng thi mao dn tng ng vi cng ti a ca ht t v ti u ho,
nhiu quy trnh to ht phi m bo chc chn t c trng thi mao dn.
V d: Mt thit b to ht c th trang b thit b o
momen xon cm nhn c s thay i trong cng
sut khuy trn yu cu trng thi mao dn.
Trong nhiu cng thc, mt hoc nhiu cu t ho
tan trong cht lng (t dc dnh) to ht t n to thnh
cht dnh khi sy kh, cc cu cht rn c to thnh
trong ht khi cc nguyn liu ho tan kt tinh hoc kt
ta li. Qu trnh ny s lm tng cng ca ht.
Trong qu trnh sy, s di chuyn ca cc cu t ho
tan ra b mt ht to nn mt b mt ht khng in hnh
c th tr gip hoc ngn cn qu trnh lm chc ht tip
theo. Tc di chuyn ca thnh phn ho tan c th
gim bng cch tng nht ca cht lng to ht v
dng t sy tng si rt ngn thi gian sy ht.
9.3.2. Tnh cht ca ht
Cn phi quan tm n mt s c tnh ca ht thnh
phm v chng nh hng ln tin trnh dp vin v tnh
cht ca vin dp ra. Cc tnh cht l:
Kh nng sp xp v c tnh chy ca ht.
xp v bn ca ht.
Hnh dng v c ht c vai tr quan trng trong kh
nng sp xp v chy ca ht, cc ht c hnh dng gn
vi hnh cu c gc chy thp hn v t trng khi cao
hn s c tnh chy tt hn. Kt qu l chnh lch
khi lng gia cc vin trong qu trnh dp vin s nh
hn, cc vin s bn chc hn.

Hnh 9.8. Cc trng thi pht trin ca ht m
khi t l cht lng c tng ln
a) Trng thi dao ng (ung a)
b) Trng thi dy
c) Trng thi mao dn
d) Trng thi git

Mc sp xp ca cc ht l quan trng trong mi quan h vi ci hoc tup phn liu, xp ca
vin trong nhiu trng hp ph thuc vo s sp xp cc ht vo ci lc ban u. Ngi ta nh gi
mc sp xp cc ht ny qua ch s nn I ni trong phn tc chy.
9.3.3. bn ca ht
Cc ht phi c mt bn thch hp chu c nhng qu trnh x l v trn bnh thng m
khng b b v v to ra mt lng ln ht mn.
Ngc li, ht cng duy tr c s nhn dng ca chng vi mt lc nn cao, nhng chc ca
vin km v tng kh nng mm vin, vin c th r ngay lp tc nhng kh nng ho tan km.
Phn b c ht c xc nh tt nht bng quy trnh
ry th nghim, s phi ch cc c ht theo mt t l
thch hp l kh ni mt cch tng qut, nhng thng
c mt t l ti u cc ht mn cn thit t c mt
s tnh cht chy ti u.

Hnh 9.9. Thit b phn loi c ht,
hiu ERWEKA hiu ERWEKA
mt kha cnh khc, s gim c ht trong khi nn
vin cng l cn thit cho lin kt ti u theo nguyn l
hn lnh c th thc hin c.
Xc nh " bn" ca ht c hiu theo nhiu
cch ph thuc vo phng php s dng ti trng th
nghim.
bn c th c biu th bng gii hn ca th
nn, ko, trt, un cong, va chm, mi mn v.v ch
c th nghim nn v mi mn thch hp trong th
nghim bn ca ht khi sn xut dc phm.
bn ca nn c th bng cch t cc ht vo
gia cc tm p v lm v n bng mt ti trng nn.
Trong nhiu cng thc ngi ta c th xc nh mt
phm vi gii hn di ca thang ny c th lm cho
vin chc hn nhng li c xu hng gim xung trong
khi trn, x l, nn s b, mn ni chung lm chm
s ng nht khi np vt liu vo y ci.

Hnh 9.10. My o mi mn, hiu ERWEKA
Th nghim mi mn theo nguyn tc nho ln ht bng mt phng php v dng c c
tiu chun ho. Kt qu th nghim gip nh gi tnh cht ca ht ng thi so snh c ngay lp tc
bn ca cc ht nhng l khc nhau.
Th nghim c tin hnh vi mt mu ht bit khi lng v t l phn b c ht trung bnh.
Sau khi tin hnh th nghim theo quy trnh nho ln trong mt thi gian nht nh (100 vng). Xc
nh t l phn b c ht, c bit l t l bt mn tng ln (mn l c ht trung bnh nh hn 75m
(200mesh) c ch nhiu.
Lng cht lng dng xt ht v nng ca t dc dnh thm vo l nhng yu t chnh lm
tng bn ca ht.
Nhng ht xp v mm cho nhng vin chc hn khi nn ti trng nh hn so vi nhng vin
c nn t ht chc v cng. Ht cm chc v cng c th lm xut hin kh nng ho tan km hn,
nhng chng t mn hn, hnh dng u hn do lp ci u hn.
9.3.4. Qu trnh dp v lm chc di ti trng cao
Trong qu trnh dp vin, nn p v y vin ra i hi s dng nhng lc nn ln gy ra cc bin
dng ht cht rn. Cc lc phi ln vt qua gii hn n hi. Cc bin dng do hoc nt gy
s a n kt qu to ra nhng b mt sch mi, khi lc nn t ti ti a s cung cp cho cu trc vt
th rn mi mt bn nht nh.
Khng ph thuc c ch lin kt, cu trc ny phi mnh chu c nhng ng sut mi xut
hin khi x nn v y vin ra khi ci. giai on ny bin dng do, thm ch xu hn l bin dng
nt gy s lm h b mt vin, nu khng b bong mt hon ton th cng c th hng ti s nt mt.
Trong khi dp vin cn ch n vng tip gip vi thnh ci, do s trt vi cng ln m cc
vng vt liu phi chu khi n b nn vo v y vin ra dc theo b mt thnh ci. iu ny s a
n kt qu c mt lp "da" vt liu chc hn b mt thnh vin, lp da ny trong mt s trng hp
c th quan st bng mt thng. Mc d lp vt liu ny mng, n vn gp phn vo chu s mi mn,
n cng c th lm chm s thot khng kh trong qu trnh dp vin v li vo ca cht lng trong khi
ho tan, c hai iu ny ta u khng mong mun. gii quyt vn , ngi ta ch dp nhng vin c
t s chiu cao v ng knh vin thp.
S khng li cc chuyn ng khc nhau ca ht gy ra bi tnh c kt vn c dn n kt qu l cc
lc khng c truyn ng nht qua ton b khi vt liu, c th trong trng hp my dp vin mt
chy, lc c s dng bi chy trn h xung tng theo lut s m khi su bn di n tng ln, do
mi quan h gia lc chy trn (F
A
) v lc chy di (F
L
) c th c din t qua cng thc:
F
L
= F
A
* e
KH/D

Trong : + K Hng s ph thuc vt liu, xc nh bng thc nghim.
+ H, D Chiu cao v ng knh ca vin.
S khc nhau gia lc ca hai chy phi c gim n mc ti thiu trong dp vin thuc khng
c s khc nhau ng k trong gi tr nn v lm chc gia vng ny v vng khc ca vin. Gim hiu
ng ma st thnh ci bng cch gim t s chiu cao trn ng knh vin v thm cht lm trn.
9.3.5. Hiu ng ma st
C hai thnh phn chnh ca lc ma st cn phi xem xt:
Ma st gia cc ht: Pht sinh do tip xc gia cc ht v c th biu din bng thut ng: H s
ma st gia cc ht (
I
), ma st ny tr nn quan trng hn khi ti trng s dng mc thp nht.
Nhng vt liu lm gim hiu ng ny gi l cht trt. Trong sn xut thuc vin thng dng
colloidial silica (Aerosil).
Ma st thnh ci l kt qu t nguyn liu ang b nn chng li thnh ci v i xung. N c
biu th bng h s ca ma st thnh ci (
w
). Ma st ny tr nn quan trng nht khi lc nn cao, khi
vic sp xp li cc ht dng li v l mt yu t quan trng trong thao tc dp vin. a s cc vin cha
mt lng nh cc cht t dc trn lm gim ma st vi thnh ci: magie stearat,...
Do s khc nhau vn c ny gia lc t ln chy trn v lc tc ng n vt liu st mt chy
di, ngi ta a ra khi nim lc nn trung bnh hnh hc (geometric mean fence).
F
G
= (F
A
x F
L
)
0,5

Dng thng s ny c l l thch hp hn dng F
A
khi xc nh mi quan h gia lc nn vin v
tnh cht bn ca vin.
(n v o lc: Niutn (N): 1N = 1kgm/s
2
,
Lc ti trng phn b u trn b mt o bng Pascal
(Pa), 1 Pa = 1N/m
2
= 1kgm/s
2
)
9.3.7. S pht trin lc hng knh (F
R
)

Khi lc nn c tng ln v s ti sp xp cc ht trong khi vt liu c hon tt, th khi
vt liu lc ny c th c coi nh l mt vt th rn n gin. Khi , nh cc vt th rn khc, lc
nn tc ng theo phng thng ng dn n kt qu lm gim chiu cao vt th mt lng H, ngha
l c mt ng sut nn xut hin. Trong trng hp vt th rn trng thi t do, iu ny s dn n s
9.3.6. Phn b lc
a s cc cng trnh nghin cu c bn v dp vin c
tin hnh trn my dp vin 1 chy hoc trn nhng b chy ci
c lp lin kt vi h thng nn thy lc.
Trn hnh 9.11 trnh by s mu ct ngang v nghin cu
dp vin vi lc tc ng t trn nh khi bt hnh tr. H
thng nn n gin ny l mt phng tin thch hp kim
tra qu trnh chi tit hn, chnh xc hn. m bo mt trc
cn bng lc, ta xem xt mi quan h c bn di y:
F
A
= F
L
F
D

F
A
Lc cung cp ln chy trn.

F
L
Phn lc c truyn xung chy di.

F
D

Phn lc ca thnh ci do ma st b mt ny.

Hnh 9.11. S ct ngang b chy ci
mu dng nghin cu nn
m rng theo chiu ngang mt lng D. T s ca hai s thay i kch thc ny c bit nh l
ch s Poisson () ca vt liu c biu din nh sau:

T s Poisson l mt hng s c trng cho mi cht rn, n nh hng ln qu trnh dp vin theo
cch sau: Do vt liu khng t do m rng theo phng mt phng ngang v n b gii hn trong ci, khi
mt lc hng knh xut hin pht trin theo phng vung gc vi b mt thnh ci. Vt liu c t
s poisson ln s lm tng gi tr ca F
R
cao hn. Thuyt ma st c in cho php suy din rng lc ma
st dc trc F
D
lin quan n lc hng knh F
R
theo biu thc:
F
D
=
W
. F
R
.

W
H s ma st thnh ci.

ch rng F
R

gim khi s dng vt liu c ch s Poisson nh v trong trng hp nh vy s truyn
lc dc trc l ti u.
Hiu ng ma st so snh bng h s ma st
W
pht sinh t s trt ca ht dnh vo thnh ci. Khi
cc ht ny trt dc theo thnh ci, ln ca n lin quan ti cng trt (S) ca cc ht (hoc s
dnh ht vo thnh ci nu cng trt yu hn) v ton b din tch tip xc c hiu qu gia hai b
mt. Do s truyn lc c thc hin khi gi tr F
D
gim xung ti thiu bng cch m bo lm trn
thnh ci mt cch y (S thp hn) v din tch tip xc c hiu qu gim. Mt phng php thng
thng so snh mc bi trn l o lc nn v lc truyn dc trc xc nh t s:

R H s hiu qu bi trn.
Khi t s t n gi tr cc i (R 1) chng t qu trnh lm trn hon thin (khng c ma st
thnh ci). Trong thc t R 0,98 c th thc hin c. Khi R < 0,8 cho ta thy mt h thng bi trn
km hiu qu.
H s hiu qu bi trn R ch c xem xt trong nhng th nghim c th, bi v chng b nh
hng bi cc bin s khc nh lc nn v t s H / D ca vin.
Bng 9.1. Cng trt ca mt s t dc trn
9.3.8. Lm trn thnh ci
a s cc cng thc vin yu cu thm t
dc trn gim ma st thnh ci. Chc nng
lm trn thnh ci c thc hin bng cch t
mt mng c cng trt thp gia b mt
phn cch ca khi vin v thnh ci. Cht lm
trn tt nht l nhng cht c cng trt thp.
Cng trt ca mt s cht thng c o
bng th nghim thm chy c ghi trong bng
9.1.
Hnh 9.12. S minh ho lm trn thnh ci
9.3.9. Lc y tho vin
Lc hng knh v lc ma st thnh ci cng nh hng ln s d dng khi tho vin dp ra khi
ci. Lc cn thit y vin ra khi ci c chia thnh ba giai on phn bit:
Giai on 1: Lc nh im khi u y vin ra bng cch b gy s dnh gia vin v thnh ci.
Giai on 2: Yu cu lc nh hn y vin thuc trt i ln theo thnh ci.
Giai on 3: nh du bng s st lc y khi vin thot ra khi l ci.
S bin i ny i khi c nhn thy r rng khi qu trnh lm trn khng y hoc iu kin
dnh trt xy ra gia vin v thnh ci do hnh thnh tip s nt ch dnh gia vin v thnh ci.
9.3.10. X nn
Trong thao tc dp vin, qu trnh nn c tip theo bng mt cng on x nn khi ti trng nn
c loi b. iu ny s khi u cho s xut hin mt ng sut mi trong vin nh l s phc hi n
hi c b sung bng lc cn thit y vin trt ra khi ci. Do cc vin phi cng v mt
c hc iu tit ng sut ny, nu khng cu trc vin s b ph hy.
Trong trng hp mc v tc phc hi cao, thm vo cng thc mt vi thnh phn bin dng
do nh PVP c th l thch hp gim nguy c phc hi dn n ph v cu trc vin.
9.3.11. bn ca vin
bn c hc ca vin c m t theo nhng cch khc nhau: bn cng, bn un, bn
gy, mi mn, bn p, v.v
a) bn p ( cng)
nh gi bn ca vin ph bin nht l bn p (Sc) c nh ngha l lc nn Fc hng theo
chiu ung knh ti vin ngay v tr ca khe nt gy. a s cc th nghim c tin hnh bng cch
t vin ln trn hoc tri chiu vi mt ci e c nh v truyn lc ti n bng cch nh mt pitton
chuyn ng cho n khi vin b nt gy.
b) mi mn
Nguyn liu
Cng trt
(MPa)
Nguyn liu
Cng trt
(MPa)
Acid stearic 1,32 Natri stearat 3,32
Calci stearat 1,47 Talc xay 6,2
Parafin cng 1,86 Talc khng xay 7,85
Magie stearat 1,96 Acid boric 7,16
Kali stearat 3,07 Graphit 7,65
Th nghim cng nhiu khi khng nh gi c
tnh trng tim n ca vin khi x l v ng gi. mi
mn b mt trong nhiu trng hp l thng s thch hp
gi tr ca F t 0,8 1,0% c xem nh l gii hn trn c th chp nhn.
c) Bong mt vin
Mt vn thng gp trong khi dp vin l s h hng cu trc vin khi y vin ra khi l ci
hoc trong cc cng on tip theo nh bao vin, l hin tng bong mt.
Hin tng ny ton b l do by khng kh trong vin, khng kh ny b nn li di mt p sut
xp x p lc nn vin, khi y vin ra n c kh nng ph v cu trc vin.
By khng kh thng xy ra vi nhng vt liu c c ht mn, c xu hng sp xp km.
Tc nn chm v s dng quy trnh nn nhiu giai on thng gim xu hng bong mt.
Tuy nhin yu t ny rt phc tp, theo mt cng trnh cng b, ngi ta chng minh rng:
Khi mt loi ht nht nh c nn di iu kin chn khng cc b tc cao, kt qu l s bong
mt c gim ti thiu nhng xu hng tch lp li tng ln.
Mt s gii php k thut gii quyt vn ny:
iu chnh cc thnh phn trong cng thc, tng cng lin kt, cung cp khung vt liu bin
dng do v gim bt ng sut n hi.
Cp nn v x ti ln khi vin dn dn hn bng cch dng trc nn ln, nn s b, nn chm
gim lc nn ti a u c khuynh hng gim bong mt,
iu chnh li t l t dc trn v m cn li trong ht.
iu kin v dng hnh hc ca chy.
C ch nn: tm sai, quay trn.
9.4. Trang b ca my dp vin
Trong sn xut dc phm ngi ta thng s dng cc my dp vin tm sai, my dp vin quay
trn v cc thit b ng nang cng c b nn phn liu.
hn.
Trong th nghim ny, o khi lng mt i trn mt
i tng vin chu mt qu trnh nho ln c chun
ho, ph bin l my th mi mn.
Ly khong 6,0g vin (W
o
) thi bi, cho vo my,
cho my quay 100 vng, ly vin ra cn li (W), mi
mn (F) tnh theo cng thc:

Hnh 9.13. My o cng, hiu ERWEKA
c mt cng ngh sn xut vin t yu cu mong
Trn hnh 9.14 gii thiu mt s mu v mt t hp chy ci c cch ly v ni vi mt my
th nghim ko nn c kh nng quan st v ghi nhn tt c cc lc khc nhau tc ng ln h thng
cng nh s di v tr ca chy.
Nhng t hp nh vy to iu kin thun li cho vic nghin cu qu trnh nn nhng tc nn
khc nhau v cung cp nhng phng tin o kim gip nhn c lng thng tin ti a trong khi s
dng lng ti thiu thi gian v nguyn liu. Chng c gi l thit b m phng qu trnh nn.

CU HI LNG GI
* Chn cu tr li sai:
1. Hin tng bt vn cc (cohesion) l do:
a) S tch tnh in gia cc ht;
b) Cc cu m gia cc ht;
c) Nng lng b mt t do ca ht;
d) a, b, c u c th xy ra.
2. Trong sn xut, o gc ngh () ca ht :
a) nh gi s ng nht gia cc l m sn xut;
b) nh gi lc c kt bn trong ca ht;
c) nh gi ma st gia cc ht;
d) bit ma st ca ht.
3. Tc chy ca ht nh hng n:
a) Khi lng trung bnh ca vin;
b) cng ca vin;
c) ng u khi lng vin;
mun, nhng phn trn chng ta kho st cc
yu t nh hng trong qu trnh nn dp to thnh
sn phm. Cc c ch to thnh lin kt, cc kiu bin
dng, qu trnh x nn, cc yu t nh hng n cu
trc vin v.v c thm thng tin v nhng yu t ,
o lc cn chy ci cng vi s di ch tng i ca
chy, to iu kin nh gi cc thng s ca qu trnh
dp vin ny, gi tr s dng my dp vin mt chy cho
s nghin cu pht trin cng thc vin sn xut trn
my quay trn tht s b gii hn. Song n ph hp vi
iu kin nghin cu s dng t nguyn liu v yu t
quy trnh cng ngh l quan trng nht, tr khi yu t ti
trng l ti hn, tuy nhin nhy cm ca cng thc
th nghim s c th nn nhng tc khc nhau v
quan st xem c nhng thay i no trong tnh cht ca
vin.

Hnh 9.14. S t hp chy ci cch ly
d) mi mn vin.
* Chn cu tr li ng:
4. Xc nh th tch ht c nhi vo ci khi dp vin ta s dng khi nim:
a) Th tch thc ca ht; c) Th tch ht;
b) Th tch khi; d) Th tch tng i;
5. nh gi t trng ca ht trc khi dp vin bng:
a) T trng thc; c) T trng ht;
b) T trng khi; d) T trng tng i;
6. Khi nim no khng phi l bin dng:
a) Bin dng nn; b) Bin dng trt;
c) Bin dng ko; d) ng sut bin dng.
7. Cu no ng:
a) Bin dng n hi khng bin mt sau khi x nn;
b) Bin dng do l bin dng bin mt sau khi loi b ti trng gy ra n;
c) Bin dng do ging nh bin dng ca l xo hay dy cao su;
d) Bin dng do l bin dng vn cn li sau khi x nn.
8. m ti u cn li trong cm dng cho dp vin l:
a) 0,02%; c) 2,0%;
b) 5,0%; d) Tu theo mt hng c th.
9. Trong k thut to ht m, trng thi lin kt ht ti u l:
a) Trng thi dao ng; c) Trng thi dy;
b) Trng thi mao dn; d) Trng thi git.
10. c tnh no ca ht khng nh hng n tin trnh dp vin:
a) Phn b c ht; c) ng knh trung bnh ca ht;
b) Tnh chy ca ht; d) xp ca ht.
11. bn ca ht thch hp cho tin trnh dp vin:
a) Ht kh dn; c) Ht rn chc;
b) Ht do; d) Ht c xp v b v cn thit.
12. Vin dp ra b nt mt l do tc ng ca:
a) Bin dng trong qu trnh nn;
b) Bin dng n hi;
c) Do ng sut mi xut hin trong qu trnh x nn v y vin ra;
d) Do cht lng ht khng t.
13. Lp da vt liu b mt bn cnh vin tc ng xu n:
a) mi mn; c) cng;
b) tan r; d) chnh lch khi lng.
14. T dc Aerosil c tc dng:
a) Gim ma st trt gia cc ht;
b) Gim ma st gia vin v thnh ci;
c) C tc dng trong tt c cc hin tng do ma st gy ra khi dp vin;
d) L mt t dc trn a nng.
15. Cn c vo cng trt, t dc trn no l tt nht:
a) Acid stearic; c) Calci stearat;
b) Magie stearat; d) Talc.
16. Hin tng bong mt vin l do:
a) By khng kh trong vin;
b) Do nhiu ht mn;
c) Do c ht qu th;
d) Do cc ht sp xp km.
17. Hin tng bm dnh (adhesion) ca bt mn nguyn liu trn b mt phu ng ht ca my dp
vin th hin:
a) Ht qu dnh;
b) Ht cha t dc trn;
c) Do tc ng ca nng lng t do b mt ca ht;
d) Do m ca ht.
18. Gc ngh ca bt phn nh:
a) nh hng ca lc c kt bn trong ht;
b) trn chy ca ht;
c) Kt qu ma st bn ngoi ca ht;
d) C a v c.
19. Tc chy ca ht phn nh:
a) nh hng ca di phn b c ht;
b) Ma st gia cc ht;
c) Hnh dng ht;
d) C a, b, c.
20. Vin nn Vitamin C 500mg, sau mt thi gian tn tr, vin b ng mu vng mt cnh vin.
Nguyn nhn l do:
a) Nguyn liu khng t yu cu cht lng;
b) Phng php pha ch khng thch hp;
c) Do chy ci khng t tiu chun;
d) Do ch bo qun khng tt.
21. Khi thay i ngun cung cp mt dc cht trong mt cng thc vin no cn:
a) Xem xt hnh dng kt tinh ca dc cht;
b) Xc nh t trng khi ca dc cht;
c) Xc nh li tan ca dc cht;
d) Thm nh li ton b quy trnh ch bin sn phm.
22. Avicel l:
a) T dc n;
b) T dc r;
c) T dc dnh;
d) T dc a nng.
23. T dc no sau y thch hp cho k thut dp vin trc tip:
a) Tinh bt m;
b) Lactose monohydrat;
c) Avicel PH 102;
d) Aerosil.
24. Nhng hot cht no sau y khng cn s dng k thut xt ht kh:
a) PenicilinV Kali;
b) Aspirin;
c) Vitamin C;
d) Paracetamol.
25. Trong k thut to ht t, trng thi lin kt ht ti u l:
a) Trng thi dao ng;
b) Trng thi dy;
c) Trng thi mao dn;
d) Trng thi git.
26. c tnh no ca ht khng nh hng n tin trnh dp vin
a) Phn b c ht;
b) ng knh trung bnh ca ht;
c) Tnh chy ca ht;
d) xp ca ht.
27. Trong qu trnh nn dp, yu t no kh xc nh nht
a) Ma st gia cc ht vt liu;
b) Di phn b c ht vt liu;
c) Tnh bin dng ca cu trc vt liu;
d) m ca vt liu.
28. Trong qu trnh to ht t cn kim sot
a) Lng dung mi a vo;
b) Thi gian to ht;
c) Trng thi pht trin ca ht m;
d) Loi cht dnh s dng to ht.

TI LIU THAM KHO
1. LEA v FEBIGER, The theory and practice of industrial pharmacy, Philadelphia, 1996.
2. Michael E.Aulton, Pharmaceutics: The Science of Dosage Form Design.

Bi 10
CNG NGH BO CH VIN NN

10.1. c im k thut ch phm thuc vin nn
Mc ch ca sn xut vin nn l ch to hng lot vin nn quy m cng nghip. Cc thnh
phm c sn xut quy m ny phi t tt c cc tiu chun k thut nh nu trong h s ng
k sn xut thuc. c c sn phm t tiu chun k thut, quy trnh sn xut phi rt n nh th
hin s ng nht ca cc vin trong cng mt l v gia cc l khc nhau.
Cc tiu chun c quy nh chung cho vin nn thng bao gm hnh thc cm quan, khi lng
trung bnh v chnh lch khi lng tng vin, ng nht v hm lng, cng, mi mn, thi
gian r, ho tan
CHNG 3
CNG NGH BO CH MT S DNG THUC
MC TIU
1. Phn tch c nhng c im thuc vin nn.
2. Trnh by c nguyn l hot ng ca my dp vin tm sai v my dp vin xoay trn.
3. Phn tch c cc tnh cht ca ht.
4. Phn tch c cc vn k thut ca cc phng php sn xut vin nn.
5. V v phn tch c s quy trnh sn xut vin nn bng phng phap xt ht t.
10.1.1. Hnh thc cm quan l mi quan tm hng u ca ngi dng thuc, do , cc vin nn c
sn xut quy m cng nghip phi khng c nhng khim khuyt c th quan st c.
10.1.2. Khi lng trung bnh
Vin nn c thit k c mt khi lng dc cht nht nh trong mt khi lng vin c
tnh ton trc. S kim tra khi lng trung bnh vin l mt bin php gin tip xc nh hm
lng dc cht. Tuy nhin, cch ngoi suy ny ch c th cho kt qu tin cy khi (a) hot cht chim
mt t l ln trong vin v (b) s phn b hot cht trong ht hoc bt dng dp vin ng nht. Dc
in Hoa K cho php dng th nghim ng nht khi lng ngoi suy hm lng khi hm
lng dc cht trn 50mg hoc t l dc cht trong vin nhiu hn hoc bng 50%.
10.1.3. Hm lng v ng u hm lng
Hm lng trung bnh. Cc Dc in u quy nh gii hn hm lng chp nhn c ca vin
nn quanh gi tr hm lng ghi trn nhn. i vi cc vin cha dc cht hm lng thp, hm
lng dc cht phi trong khong 90 110% so vi hm lng ghi trn nhn. i vi cc vin c hm
lng trung bnh v cao, hm lng dc cht phi trong khong 95 105% so vi hm lng ghi trn
nhn. xc nh hm lng trung bnh, c mu phi ly ti thiu l 20 vin, tuy nhin trong nhng
trng hp vin c hm lng thp (v d vin Digitoxin), phi ly s vin sao cho tng hm lng
t n 5mg v lng mu cn cho mt ln xc nh phi t n 2mg hot cht.
ng u hm lng. ng u hm lng c xc nh bng cch nh lng tng vin
mt, vi c mu 10 vin. Vin c xem l t ng u v hm lng khi c t nht 9 vin c hm
lng nm trong gii hn cho php v lch chun tng i nh hn hoc bng 6%. Trng hp
khng t c th thc hin thm vi 20 vin v kt qu c xem l t nu khng c vin no trong s
20 vin th ln hai nm ngoi gii hn cho php v lch chun tng i tnh trn 30 vin khng qu
7,8%.
t c tiu chun v ng u hm lng, nht l i vi nhng vin c hm lng nh,
quy trnh sn xut phi ht sc n nh sao cho (a) s phn phi dc cht trong khi ht trc khi dp
vin l ng nht, (b) hn hp ht khng b tch lp trong nhng giai on khc nhau ca quy trnh sn
xut v (c) sai s khi lng nm trong gii hn cho php.
10.1.4. cng v mi mn l hai thng s quan trng nh gi bn c hc ca vin nn. Ch
tiu v cng cha c quy nh c th trong cc Dc in, tuy nhin cng c lin quan cht ch
n cht lng ca thuc nh thi gian r v ho tan, nn thng s ny phi c quan tm ngay t
giai on u tin ca qu trnh nghin cu xy dng cng thc.
Cho n nay c nhiu loi thit b ca nhiu nh sn xut khc nhau c dng trong cng nghip
dc xc nh cng. Cc thit b o cng khc nhau c th c nguyn l hot ng khc nhau,
do , c th cho nhng kt qu khc nhau. n v o cng thay i theo nh sn xut, cc n v
thng dng gm:
1kP (KiloPound) = 1kgf = 9,807N
1 SCU (Strong Cobb Unit) = 0,714kP
mi mn. Cc vin nn thng c khuynh hng mn, m cnh hoc nt khi chu cc tc ng
c hc. Nhng thay i ny lm vin thi bi ra gy nhim cho trong qu trnh sn xut, ng thi
cng nh hng n khi lng vin. mi mn phn trm l mt ch tiu nhm nh gi kh nng
chu va p ca vin trong qu trnh sn xut. Vin nn thng thng nu c mi mn phn trm
n 0,5% hoc n 1% (tu theo quy nh ca nh sn xut) v khng nt, m cnh, bong mt c xem
l t mi mn. Vin nn dng bao phim hoc bao ng nn c mn thp (t hn 0,2%). Th
nghim mi mn thng c tin hnh trn 10 vin nu vin c khi lng ln hn hoc bng
650mg, i vi vin c khi lng nh hn 650mg phi ly s vin sao cho tng khi lng t t nht
6,5g.
10.1.5. Thi gian r ( r)
c th hp thu, dc cht phi c ho tan trong dch tiu ho. i vi nhiu thuc thng
thng, vin phi r thnh cc tiu phn nh trc khi c ho tan. Trn thc t, kh c th xc lp
c mi tng quan gia thi gian r v ho tan, tuy nhin s r l giai on gii hn tc ho
tan, nht l i vi nhng dc cht kh tan trong nc. V vy, mc d hin nay Dc in dn dn
thay th th nghim r bng th nghim ho tan, nhng th nghim xc nh thi gian r vn l mt
ch tiu cn c quan tm trong nghin cu nhm xy dng cng thc ti u nht, ng thi l mt
phng tin nh gi quy trnh sn xut thuc, m bo ng nht ll.
10.1.6. ho tan
Cc vin nn dng ng ung phi ho tan dc cht trong dch tiu ho c th c hp thu.
Mc tiu chnh ca th nghim ho tan trong sn xut l chng minh (a) dng thuc c th phng
thch c gn 100% dc cht ra khi dng thuc v (b) tc ho tan dc cht ng nht t cc l
khc nhau trong qu trnh sn xut v tc ho tan ny tng t nh tc ho tan ca l thuc
dng trong nghin cu tng ng sinh hc v th nghim lm sng.
10.1.7. n nh
Ngoi cc th nghim c quy nh trong Dc in, nh sn xut cn phi chng minh n
nh ca ch phm, hn dng ca sn phm phi c xc nh cn c vo th nghim n nh y
v ng quy nh v s lng l, c l, thi im ly mu, thi gian th nghim n nh ca
ch phm phi c chng minh bng s n nh ca dc cht v n nh v cc ch tiu vt l ca
dng thuc nh cm quan, thi gian r, ho tan
Khi kim tra cc ch tiu k thut, cc vin trong cng mt l thng c ly kim tra. Tuy
nhin, m bo mt quy trnh sn xut c tnh n nh v cho ra nhng sn phm c cng mt cht
lng v cht lng phi duy tr n hn dng d kin cn phi quan tm n cc vn sau:
ng u gia cc sn phm trong cng mt l.
n nh gia cc l sn xut.
Hn dng.
Bao b, ch bo qun v vn chuyn.
c th t c tt c cc yu cu v tiu chun cht lng ca thuc v c mt quy trnh sn
xut n nh, cn phi c nhng nghin cu chi tit v khoa hc nhiu giai on khc nhau trc khi
a quy trnh vo sn xut.
10.2. Cc nghin cu xy dng quy trnh sn xut vin nn
10.2.1. Kho st cc tnh cht l ho ca dc cht
Cn c gi l nghin cu tin cng thc (preformulation) v l giai on u tin trong qu trnh
nghin cu quy trnh sn xut mt dng thuc. Mc tiu ca giai on ny l kho st cc tnh cht l
ho ca dc cht v s thay i cc tnh cht l ho c th xy ra khi kt hp vi t dc hoc do tc
ng ca quy trnh sn xut. Kt qu ca nghin cu l c s la chn t dc v xut phng
php sn xut vin nn, ng thi cng c th d on c cc tnh cht sinh dc hc ca thnh
phm. Mi loi dc cht c nhiu tnh cht l ho, cc tnh cht ny i khi thay i tu thuc vo k
thut ca nh sn xut nguyn liu. Do , trong trng hp thay i ngun cung cp nguyn liu, mt
vi tnh cht c th phi kho st li trc khi ng dng vo sn xut.
a) tinh khit
Kho st u tin khi nghin cu tnh cht l ho ca dc cht l tinh khit. Cc th nghim ny
nhm mc ch pht hin cc cht thoi ho v cc cht l c trong Dc cht. Mt s chuyn lun ca
Dc in c ghi phng php kim nh cc cht khng tinh khit. Trng hp khng c ghi trong
Dc in c th dng cc phng php nh o im chy, pH, xc nh kim loi nng, phng php
sc k lp mng
Trong sn xut vin nn khng cn phi nghin cu su v tp cht v cc cht lin quan nhng phi
c nhng hiu bit nht nh v tp cht v cc cht lin quan c th hin din trong dc cht. Cc
dc cht c tp cht vn c th c dng nghin cu, sn xut vin nn nu lng tp cht trong
gii hn cho php. Tuy nhin, vi tp cht trong nguyn liu c th nh hng n n nh ca ch
phm, nht l cc kim loi nng c th xc tc phn ng thu phn hoc oxy ho. Tp cht c th lm
thay i mu sc, mi v ca ch phm; mt s tp cht c th l cht c (cc amin mch vng l cc
cht c th gy ung th).
b) Mu, mi, v
Cn phi ghi nhn mu sc ca cc l thuc th nghim u tin v xem l mt tiu chun k
thut v phng din cm quan cho cc l thuc sau. Cn phi kim tra n nh ca mu. Trng
hp mu ca dc cht khng bn hoc khng p cn phi thm cc cht mu khc ci thin cm
quan hoc bao vin.
Nu dc cht c v ng th nn dng dng mui t tan hn nhng khng nh hng n sinh kh
dng ca thuc. Nu dng mui khc khng ph hp, c th bao vin che lp v ng.
Dc cht c mi kh chu c th ci thin mi bng cch cho thm cc cht thm hoc bao vin.
c) Kch thc tiu phn, hnh dng v din tch b mt
Kch thc tiu phn c nh hng ln n sinh kh dng v hiu lc iu tr ca thuc, c bit l
cc dc cht c tan l giai on gii hn tc hp thu. Cc dc chat kh tan c th c nghin
mn n dng siu mn lm tng tan v ci thin sinh kh dng (v d: griseofulvin, phenacetin).
K thut iu ch vin nn cng b chi phi bi kch thc tiu phn. Cc vin c hm lng nh
cn phi s dng dc cht c nghin tht mn, tuy nhin nghin mn qu nh li kh trn do nh
hng ca lc ht tnh in. Mt s dc cht khng bn vi iu kin mi trng khi c nghin qu
nh. Do , cn xc nh khong kch thc tiu phn ti u cho tng loi sn phm.
d) tan
Mt trong nhng yu t nh hng ln n s hp thu thuc l tan ca dc cht trong mi
trng dch tiu ho. Thng thng cc vin nn cha lng dc cht c th ho tan c hon ton
trong 250ml nc c pH trong khong 1 8 s khng gp vn ln trong sinh kh dng, tuy nhin cn
phi lu n liu v n nh ca dc cht trong dch tiu ho.
Trng hp dc cht c tan thp cn thay i dng mui hoc nghin mn dc cht hoc phi
hp vi mt cht mang thch hp iu ch dng phn tn rn.
e) Tng tc gia dc cht v t dc
Cc tng tc ho hc v vt l xy ra gia dc cht v t dc c th lm hng dc cht hoc
nh hng n cm quan ca dc cht. Cc tng tc dc cht t dc thng xy ra nhanh khi cc
thnh phn c hm m cao hoc khi cc thnh phn trong vin tip xc vi m ca mi trng trong
cc giai on ca quy trnh sn xut hoc trong thi gian bo qun. Cc tng tc ho hc c th c
pht hin bng cch gia tng nhit phn ng xy ra nhanh. Cc tng tc vt l (v d chy lng
hoc bay hi) thng kh pht hin c bng phng php lo ho cp tc.
g) Dng tinh th
Mi dc cht c th tn ti di mt dng tinh th hoc phi hp nhiu dng tinh th (a hnh).
Cc dng tinh th khc nhau thng c tan khc nhau nn s hp thu thuc c th khc nhau. Mt s
dc cht tn ti nhiu dng tinh th khc nhau v c bn khc nhau.
10.2.2. Nghin cu xy dng cng thc v quy trnh sn xut
Nghin cu xy dng cng thc l nghin cu cn bn v l giai on quyt nh trong sn xut vin
nn. Mc tiu ca nghin cu xy dng cng thc l nhm la chn loi v t l t dc, ng thi la
chn quy trnh iu ch thch hp.
Khi la chn t dc cn quan tm n cc yu t: tnh cht l ho ca dc cht, ngun nguyn
liu n nh, gi thnh r, v nhiu yu t khc lin quan n cht lng sn phm v quy trnh sn xut.
S ph hp vi tnh cht ca dc cht. Ngoi s tng k ho hc vi dc cht, cn phi quan
tm n cc nh hng ca t dc n dc cht v phng din vt l. Sau khi kho st cc tnh cht
ca dc cht, c th chn mt phng php iu ch vin, t c th chn cc t dc thch hp.
nh hng n tc phng thch dc cht. S la chn t dc tu thuc vo dng vin nn
phng thch tc th (immediate release) hay phng thch ko di (sustained release). Cc vin phng
thch tc th thng phi dng t dc r vi t l ln hoc dng t dc siu r, dng vin phng thch
ko di thng phi dng cc polyme hoc sp lm chm tc phng thch dc cht. Trong trng
hp yu t gii hn tc hp thu dc cht l tan, cn thit phi s dng cc t dc lm tng tc
ho tan hoc lm tng tc hp thu. Cc t dc siu r c th c dng trong vin nn cha dc
cht t tan, i khi c th s dng thm cc cht din hot cc cc tiu phn dc cht d thm t
khi tip xc vi dch tiu ho.
Thun li cho quy trnh sn xut. Cc t dc c chn phi gip cho vic iu ch ra vin nn t
cc ch tiu cht lng theo Dc in hoc tiu chun c s. Cc t dc c chn phi d mua, c
tnh n nh cao v d phi hp vi dc cht. Tiu chun ca thnh phm phi c xy dng ngay t
khi bt u nghin cu xy dng cng thc. Quy trnh sn xut phi c kim sot cht ch ngay t
u nhm m bo cht lng ca sn phm v ra nhng ch tiu kim tra, kim sot trong qu trnh
sn xut.
Tnh kinh t cao. Gi ca nguyn liu v cc chi ph trong qu trnh sn xut phi c tnh ton khi
nghin cu xy dng cng thc v quy trnh sn xut. Nhiu nh sn xut a chung phng php dp
thng d cc t dc dp thng gi cao hn, nhng vn r hn khi so snh vi mt quy trnh nhiu cng
on nh xt ht t hoc xt ht kh.
10.2.2. Thnh phn thuc vin nn
a) Dc cht
Yu cu chung dc cht trong dng vin nn l phi tan trong dch tiu ho c th c hp thu.
Tuy nhin, thuc vin nn c th cha dc cht khng tan nhm cho tc dng iu tr ti ch (thuc
khng acid, thuc tr bnh ng tiu ho). Vi cc thuc cha dc cht khng tan, tc ng tr liu
ph thuc vo din tch b mt, vin nn phi c thit k sao cho r nhanh v phn tn u trong dch
tiu ho vi din tch tip xc ln nht.
Vin nn l dng thuc rn cha nhiu loi t dc. S la chn loi, t l v cch phi hp cc t
dc trong k thut iu ch vin nn ph thuc vo tnh cht l ho, c liu v tnh cht hp thu ca
dc cht. Cc dc cht c hot tnh mnh, dng liu thp cn phi c phn tn mn m bo
ng nht hm lng. Tng t, cc dc cht dng khng acid hoc tc dng ti ch ti ng tiu ho
cn c nghin mn cho din tch tip xc ln.
Cc dc cht c tan cao v dng liu ln vn c th c sinh kh dng km do nh hng ca cc
t dc khc c trong cng thc.
b) Cc t dc
Cc t dc thng c phn loi theo chc nng chnh khi hin din trong vin nn, tuy nhin vn
c nhiu t dc c nhiu chc nng khc nhau. Vin nn cha nhiu loi t dc khc nhau, v hu
nh tt c cc loi t dc u nh hng n sinh kh dng ca thuc cc mc khc nhau. Hiu
bit v tnh cht ho l, i khi c tnh cht sinh hc, ca t dc l yu t quan trng khi nghin cu
xy dng cng thc.
c) T dc n
T dc n c dng trong trng hp dc cht khng dp thnh vin hoc pha long
trong trng hp dc cht c hot tnh mnh.
Cc t dc n thng c xem l cc t dc tr, tuy nhin chng c th nh hng n tnh
cht lho v sinh kh dng ca vin nn: Hm m trong t dc n l nguyn nhn ch yu lm
dc cht khng n nh. Khi nghin cu xy dng cng thc, cn phi quan tm n hm m, kh nng
gi m v hp thu m ca t dc n. Trong nhiu trng hp, s hp thu nc v mt nc khng
phi l mt qu trnh thun nghch nn kh c th loi m hon ton bng cc phng php sy thng
thng (t sy hoc my sy tng si). S hp thu nc ca t dc n ph thuc vo m v nhit
ca mi trng. Hm m cn li trong ht c nh hng n tnh cht vt l ca vin nn; vi mt
hm m nht nh lng nc trong vin c tc ng nh t dc dnh. Trn thc t kh c th sn xut
vin nn c mi mn thp khi dc cht nhy cm vi m.
Khi la chn t dc n, cn lu n tnh cht t do hay lin kt ca m. Calci sulfat dihydrat c
cha 12% nc kt tinh, tuy nhin nc ny ch phng thch khi nhit ln n 80
o
C, cao hn nhit
bo qun bnh thng rt nhiu, nn vn thch hp vi dc cht nhy cm vi m.
Mt s t dc n thng dng:
Lactose l t dc n thng dng nht, gm hai dng l dng khan v dng ngm nc, c hai
dng u ph hp vi a s dc cht. Lactose ngm nc c cha 5% nc kt tinh, thng dng
trong phng php xt ht t. C nhiu dng khan v dng ngm nc c sn xut bng nhiu
phng php kt tinh hoc sy khc nhau. Lactose c nhiu c ht ph hp vi nhiu phng php sn
xut vin nn. Lactose gip vin phng thch hot cht nhanh, d sy ht v cng ca vin t ph
thuc vo t l lactose c trong vin.
Lactose tng k vi nhng dc cht cha nhm amin v t dc trn bng c tnh kim.
Lactose khan khng cho phn ng Millard, gip vin r nhanh, mi mn thp, t b m hoc t
chm.
Lactose phun sy c dng gn nh hnh cu nn c lu tnh tt, c tnh chu nn cao, do thng
dng trong phng php dp thng (dng ring hoc phi hp vi cellulose vi tinh th). Khi dng ring
nn s dng vi t l khong 40 50%, tnh chu nn ca lactose phun sy gim khi b mt nc.
Lactose phun sy b ng mu khi phi hp vi cc dc cht c hm m cao hoc cc amin, cc
dc cht mang nhm phosphat, lactat, acetat. trnh hin tng vin ng mu nn dng t dc trn
bng l acid stearic hn l dng stearat kim.
Vin nn c iu ch t lactose phun sy c bn c hc cao hn khi iu ch bng cc loi
lactose thng thng, nhng vin d b vng hn.
ng saccharose. ng c s dng ch yu trong iu ch vin nn nhai hoc vin ho tan
trc khi ung. ng saccharose c th c dng di dng bt mn hoc dng ht trong vin nn
dp thng. Hin c loi ng dp thng vi tn thng mi l DiTab, NuTab.
Glucose (Dextrose). C v ngt v d tan nn thch hp cho vin nhai hoc vin ho tan trc khi
ung, thng c dng nh t dc n v dnh trong phng php dp thng hoc xt ht.
Mannitol. Thch hp cho vin nhai v ngm do li cm gic mt lnh khi tan ming. Lu tnh
ca mannitol rt km, nn nu dng cho phng php dp thng phi thm nhiu t dc trn bng.
Trn th trng cng c loi mannitol dp thng, c ch to bng phng php kt tinh c bit,
mannitol thch hp vi cc dc cht d h bi m, RH=90%, mannitol ch ht m khong 1%.
Sorbitol l ng phn quang hc ca mannitol, ht m rt mnh nu hm m tng i ca mi
trng 65%.
Tinh bt: c dng lm t dc n, r v dnh. Vin nn c s dng nhiu tinh bt c khuynh
hng mm v kh sy ht. Hm m trung bnh ca tinh bt trong khong 11 14%, mt s tinh bt sy
c bit c hm m 2 4%, khng nn dng tinh bt loi sy c bit lm t dc trong phng php
xt ht t do cc k thut sy thng thng ch c th lm cho ht t hm m trong khong 68%.
Mc d c m cao (1114%), tinh bt li c tc dng nh mt cht ht m n nh cc dc
cht nhy cm vi m.
Tinh bt dp thng c bn vi tn thng mi l Starch 1500 l loi tinh bt c tnh trn chy tt
v c tnh chu nn cao. Tinh bt 1500 c dng nh t dc n trong vin nn dp thng, t dc r,
ng thi c th c dng nh t dc trn nu dng t l cao hn 10% trong vin nn.
Cellulose vi tinh th, tn thng mi l Avicel, l mt loi t dc n kh t nn t khi c
dng ring m thng phi hp vi cc t dc khc ci thin tnh cht ca vin. C nhiu loi
Avicel khc nhau dng cho nhng phng php dp vin khc nhau: Avicel PH 101 dng cho phng
php xt ht t, Avicel PH 102 dng cho phng php dp thng v xt ht kh Avicel cn c
dng nh t dc dnh v t dc r.
Vin nn c Avicel hm lng cao c th b mm khi bo qun mi trng c m cao.
Dicalci phosphat. C hai dng dicalci phosphat khan v ngm nc u c tnh chu nn rt tt,
gi r nn c s dng nhiu. Vin iu ch bng t dc n ny thng r km, nn thng phi
phi hp vi cc t dc r mnh.
Tricalci phosphat l hn hp ca tricalci ortho phosphat v calci phosphat, cng dng ca cht ny
tng t nh dicalci phosphat, thng dng trong vin nn cha vitamin v nguyn t vi lng v va
cung cp calci va c tc dng nh t dc n.
Magie carbonat c s dng lm t dc n trong vin nn dp thng. T dc ny c tnh
thm ht mnh nn thch hp cho vin nn cha cc cht lng nh tinh du, cao dc liu.
Cc t dc n khc: Magie oxyd, calci lactat tribasic.
d) T dc dnh
Gip cho cc tiu phn rn lin kt li vi nhau to thnh ht hoc vin c cng thch hp. T
dc dnh c th c dng di dng bt mn hoc pha thnh dung dch hoc hn dch. Dng dng ph
thuc vo phng php sn xut c p dng v tnh cht l ho ca dc cht. T l s dng ph
thuc vo tnh cht ca dc cht, phng php xt ht v tnh cht ca my dp vin.
Mt s t dc dnh thng dng:
Gm Arabic dng di dng bt mn t l 2 3%, hoc dng di dng dch th 10 30%. Gm
Arabic cho vin c cng ln, kh r, nn thng phi phi hp vi t dc dnh khc.
H tinh bt dng dng dch th 5 10%.
Tinh bt tin gelatin ho dng dng bt mn trong phng php dp thng hoc dng dch th
trong cc phng php xt ht.
Acid alginic dng dng bt t l 1 5%, cn dng lm t dc r vi t l tng t.
Gelatin c dng di dng dung dch 3 20%, cn cho thm cht bo qun nh nipagin,
nipasol, natri benzoat. Gelatin c tnh dnh tt nhng lm vin kh r.
Glucose c dng di dng bt mn trong phng php dp thng.
Methyl cellulose (Tylose) dng dng bt mn hoc dung dch trong cn.
CMC hoc Na CMC thng dng dng dung dch trong phng php xt ht t.
Cellulose vi tinh th (Avicel) l t dc dnh rt tt dng cho vin nn dp thng v xt ht kh.
Polyme acrylate: loi thng s dng nht trong nhm lm t dc dnh l Eudragit E c
dng dng dung dch 5 20% trong cn.
Polyvinyl pyrrolidon (PVP) dng dng dung dch 5 10% trong cn hoc hn hp cnnc.
PEG 4000 hoc PEG 6000 dng dng dung dch trong cn hoc nc.
Cc t dc dnh c ngun gc t nhin (h tinh bt, gm arabic, gelatin) thng khng n nh v
cht lng gy kh khn cho qu trnh sn xut v nh hng n cht lng vin nn hin nay t c
dng.
e) T dc r
Cc loi t dc r ph bin hin nay l:
Tinh bt cc loi (ng, sn, khoai ty, la m).
Sodium starch glycolat (Explotab, Primogel, DST).
Tinh bt bin tnh.
Tinh bt bp bin tnh (Starch 1500).
Algins (natri alginat)
T dc r thng c trn chung vi cc thnh phn khc trc khi xt ht (t dc r ni). Tuy
nhin t dc r c th cho thm sau khi xt ht (t dc r ngoi) gip cho vin nn r d dng hn
khi tip xc vi dch tiu ho hoc mi trng th, hoc c th chia t dc r thnh hai phn vin
va c t dc r ni va c t dc r ngoi, khi vin s r tt hn.
g) T dc trn bng
T dc trn c bn chc nng:
To kh nng trt gia cc ht, lm tng lu tnh ca ht, gip vin t ng u khi lng.
Tng kh nng chng dnh, lm cho cc ht bt dnh vo chy ci.
Tng kh nng chng ma st, lm gim ma st gia cc tiu phn ht khi dp vin do truyn
sc p vo khi ht c tt hn.
To bng, to cho vin mt v p, bng lng.
Cc t dc trn bng c phn loi nh sau:
Nhm gip cho s chy ca ht (Trt, glidants): Talc, aerosil, acid boric, calci stearat, Mg
stearat, Zn stearat, PEG 4000, PEG 6000.
Nhm cht chng dnh (Antiadhesives): Acid stearic, aerosil, talc,...
Nhm cc cht trn (Lubricants): Talc, magie stearat, natri lauryl sulfat.
i vi cc vin nn pha thnh dung dch hoc vin si bt, cn chn loi t dc trn bng tan
c trong nc nh acid boric, natri borat, natri lauryl sulfat, PEG 4000 hoc PEG 6000
h) Cc t dc khc
Cht bo qun: Nipagin, nipasol, natri benzoat.
Cht chng oxi ho: Natri bisulfit.
T dc m: Calci carbonat, calci triphosphat, natri citrat.
T dc mu: Mu thin nhin, mu v c, mu hu c tng hp (tan trong nc v khng tan
trong nc).
T dc mi: Cc loi tinh du t nhin, tng hp, vanilin.
T dc to v: cc loi ng (glucose, sorbitol, saccharose, saccharin, Na saccharin, aspartam,
kali acesulfam, Na cyclamate).
i) Bao b dng cho vin nn
Bao b l mt thnh phn ca dc phm, c cc chc nng sau:
Gip nhn bit, nh danh sn phm.
Bo v bo qun thuc.
Thun tin cho vn chuyn thnh phm.
To thun li cho ngi tiu dng.
Tng cng v m quan thu ht ngi tiu dng.
Cc nguyn liu dng lm bao b phi c cc tiu chun sau:
R tin.
Khng c.
C bn c hc cao.
Khng thm m hoc thm m mt mc chp nhn c.
Khng tng tc, khng nh mi, khng nh mu, khng hp ph mi ca thuc.
D nh hnh trong cc my p v.
D in ch hoc cc logo.
Ph hp vi cc my ng bao b, t l loi thp.
D m v d ng (chai l), c kh nng ngn nga tr em.
D sn xut v d bo qun (chng c nhim bn v vi sinh vt).
Cc loi nguyn liu dng ch to bao b vin nn bao gm: Giy, carton, thu tinh, kim loi, nhm
l, bng, cc loi nha.
k) Nguyn liu lm chai ng thuc vin
Thu tinh. Nguyn liu c ngun gc v c, khng thm m v kh. Hu nh khng tng tc vi
bt k nguyn liu no. Thu tinh mu h phch c kh nng chng nh sng.
HDPE (High density polyethylen) v PE (Polyethylen): Nh, d bo qun, vn chuyn. Kh nng
chng m ca nha polyethylen rt km.
l) Nguyn liu lm v bm
Lp v trn
PVC (Polyvinyl clorid): Nhit nh hnh trong khong 120 140
o
C, thch hp cho tt c cc my
p v. Kh nng chng m km.
PP (Polypropylen): Nhit nh hnh trong khong 140 150
o
C, i hi my p v phi gia nhit
nhit cao v chnh xc, c hin tng co ko lm nhn v ngay sau khi to hnh. Chng m tt v
khng sinh clo khi t, c s dng nhiu chu u.
PVC trng PVDC (Polyvinyliden clorid): Kh nng chng thm m cao, PVDC c trng mt
trong (mt tip xc vi thuc).
PET (Polyethylen terephtalate) v PS (Polystyren): To hnh rt d nhng kh nng chng m rt
km.
Bng 10.1. Tnh thm m ca mt s plastic
Mt lng. Thng lm bng giy nhm, giy nhm trng PET hoc giy trng nhm v PET. Tnh
chng m tu thuc vo dy ca mng nhm, mng nhm dy t 25m tr ln hu nh khng thm
m.
m) Nguyn liu lm v x
Nguyn liu lm v x c th l plastic hoc giy nhm trng plastic tu thuc vo yu cu chng m
ca ch phm. V x thch hp cho vin c kch thc ln hoc vin cn chng m tt.
10.3. Yu cu cn bn trong sn xut vin nn
10.3.1. Quy trnh sn xut
Cng thc v quy trnh sn xut phi c tnh kh thi, ph hp vi iu kin trang thit b ca c s
sn xut. Cn phi c s phi hp cht ch gia cc nh nghin cu xy dng cng thc v nhn vin
cc b phn sn xut. Yu cu ny rt quan trng khi xy dng mt quy trnh sn xut vi mt thit b
Loi plastic Tc thm m
(g/ 100 inch
2
/ 24 gi)
HDPE 0,3
LDPE 1,3 1,5
PP 0,7
PS 7 10
PVDC 0,2 0,6
PVC 2,0 5,0
mi hoc s dng t dc mi.
10.3.2. Thit b
La chn ng thit b, vn hnh thit b thnh tho, bo qun thit b tt l mt yu cu quan trng
cn phi quan tm ngay t khi xy dng quy trnh sn xut. Ngi tham gia vo dy chuyn sn xut
khng nhng phi am hiu v thit b chu trch nhim chnh m cn phi c nhng hiu bit nht nh
v nhng trang thit b phi dng trong quy trnh sn xut.
10.3.3. Nh xng
Nh xng phi c xy dng theo nhng yu cu ca GMP. Din tch xy dng phi ph hp cho
tng cng on ca quy trnh. Vt liu xy dng phi khng c hp ph, nh mi hoc c th phn
ng vi nguyn liu.
Khi thit k tng th v cc b phn trong phn xng thuc vin nn phi lun lun ch chiu di
chuyn ca nguyn vt liu v phi kim sot c s nhim cho. Mc tiu quan trng nht l c s
cch ly gia cc sn phm ang trong giai on bit tr v sn phm khng t tiu chun. Tu thuc
din tch sn c v nhu cu sn xut c th thit k khu vc sn xut theo cc m hnh sau:
a) Khu vc sn xut bao quanh kho trung tm (perimeter manufacturing center warehouse)

Hnh 10.1. S thit k theo m hnh Khu vc sn xut bao quanh kho.
(1) Vn phng; (2) Phng tip nhn nguyn liu; (3) Bit tr nguyn liu; (4) Phng bao vin;
(5) Khu vc nn vin; (6) Khu vc xt ht; (7) Kho cha nguyn liu c chp nhn;
(8) Phng cha sn phm bit tr; (9) Kho cha sn phm c c duyt;
(10) Cp pht nguyn liu; (11) Khu vc sn xut thuc dng lng hoc bn rn; (12) Khu vc ng gi;
(13) Phng in v cp pht nhn; (14) Khu vc giao thnh phm.
M hnh ny c s dng tng i ph bin. c trng ca m hnh l khu vc trung tm s l
kho cha nguyn liu sn xut, nguyn liu ng gi; cc khu vc sn xut v ng gi c thit k
xung quanh kho. Nguyn ph liu dng cho sn xut s di chuyn t khu vc tip nhn v bit tr vo
kho. Nguyn liu s c cn v cp pht vi lng ph hp vi l sn xut v c chuyn thng vo
khu sn xut. Sau khi hon thnh sn xut, sn phm c chuyn vo kho bit tr v c chuyn vo
kho thnh phm khi c phiu xut l. Khi c lnh ng gi, nguyn liu ng gi v vin s c cp
pht v chuyn vo khu vc ng gi.
u im ca m hnh thit k ny l tit kim c din tch v khu vc cp pht gn k khu vc
sn xut. Tuy nhin, ng di chuyn ca cc sn phm (hoc nguyn liu) ct cho nhau nn c th gy
ra nhim cho hoc nhm ln.
b) Di chuyn theo ng cong (circular flow)

Hnh 10.2. S thit k theo m hnh Di chuyn theo ng cong
(1) Vn phng; (2) Phng tip nhn nguyn liu; (3) Bit tr nguyn liu; (4) Nguyn liu c
chp nhn; (5) Cp pht nguyn liu; (6) Khu vc xt ht; (7) Khu dp vin; (8) Phng bao vin;
(9) Khu vc sn xut thuc lng v bn rn; (10) Nguyn liu ng gi c duyt cp;
(11) Bit tr bn thnh phm; (12) Khu vc ng gi; (13) Phng in v cp pht nhn;
(14) Khu vc giao thnh phm.
Theo thit k ny, khu vc cha nguyn liu v ph liu duyt pht v khu vc cp pht c b
tr nm hn v mt khu vc c ngn cch vi khu sn xut, bit tr thnh phm, kho bn thnh phm
v ng gi bi mt hnh lang. ng di chuyn ca nguyn vt liu tng t nh m hnh kho trung
tm. Tuy nhin, nguyn vt liu ch di chuyn theo mt chiu, nn hn ch c s nhim cho hoc
nhm ln.
c) Di chuyn theo ng thng (straight line flow)
Nguyn vt liu c di chuyn theo ng thng. S nhim cho trong trng hp ny c hn
ch n mc ti thiu. Thit k ny c nhc im l cn nhiu din tch.

Hnh 10.3. S thit k theo m hnh Di chuyn theo ng thng
(1) Vn phng; (2) Phng bao vin; (3) Phng in v cp pht nhn; (4) Phng nn vin;
(5) Khu vc xt ht; (6) Cp pht nguyn liu; (7) Nguyn liu c chp nhn;
(8) Bit tr nguyn liu nhn; (9) Khu vc tip nhn nguyn liu;
(10) Khu sn xut thuc lng v bn rn; (11) Nguyn liu ng gi duyt cp;
(12) Bit tr bn thnh phm; (13) ng gi; (14) Khu vc giao thnh phm.
Mt trong nhng vn phi quan tm hng u trong thit k c s sn xut dng phn liu rn l
h thng x l khng kh. C s phi c thit k sao cho khng kh trc khi vo cc phn xng
phi qua h thng lc, n cc khu vc vi cc p sut khc nhau sau c lun chuyn tun hon ra
khi phn xng.
Khu vc cn v cp pht nguyn liu phi l khu vc kn c nhng trm hoc bung cn ring bit
thao tc cn v ly mu c th c tin hnh trong cng mt thi im. Khu vc ny c th c
thit k vi nhng lung khng kh tri thnh lp mng di chuyn theo chiu ngang hoc c cc thit b
thu ht bi. Khng kh cung cp cho khu vc ny phi c lc qua h thng lc HEPA.

Hnh 10.4. S h thng kh trong khu vc dp vin

Hnh 10.5. H thng ht bi trong khu vc cn v ly mu nguyn liu

Hnh 10. 6. Bung cn nguyn liu
Khi thit k khu vc xt ht phi quan tm n lung di chuyn ca nguyn liu. Khi nguyn liu di
chuyn d dng vo cc khu vc ch bin th kh nng nhim s gim. Thng thng p sut trong
khu vc trn v xt ht phi thp hn hnh lang pha ngoi trnh bi thuc thot ra hnh lang.
Mi my dp vin phi c t trong mt phng ring. Phng cha my dp vin c th c kch
thc khc nhau ph hp vi kch c ca my dp vin. Nu c th, my dp vin nn c t trn mt
k kim loi chc chn, k ny c th di chuyn d dng bng xe nng dng in a n khu vc v
sinh my v thay chy ci (thay v v sinh v lp rp chy ci ti phng dp vin). Cc phng cha my
dp vin nn c p sut thp hn p sut hnh lang trnh bi thot ra hnh lang gy nhim bi sang
cc phng khc khi m ca phng dp vin. Phng dp vin cn m thp phi c xy dng bng
vt liu c tnh thm m rt thp v nn c cht gi (airlock). Khng kh cung cp cho cc phng ny
phi c lc s b ngay ti thit b thu ht bi v c lc, sau qua h thng lc HEPA.
m v nhit trong khu vc sn xut vin nn phi c duy tr va bo m nguyn liu v
ch phm khng b hng, ng thi phi to cm gic d chu cho cng nhn tham gia v dy chuyn
sn xut. Ngoi tr nhng trng hp c bit, phng dp vin v bao vin nn c duy tr nhit
25
o
C v m tng i khong 45%.

Hnh 10.7. S mt khu vc dp vin
10.3.4. Nhn s
Phi c y nhn s tt c cc giai on ca quy trnh sn xut. Tt c cc nhn vin tham gia
vo sn xut phi c hun luyn hon thnh cng vic theo ng chc nng xc nh.
Nhn s tham gia dy chuyn sn xut vin nn gm:
Nhn vin vn hnh my trn, xt ht, dp vin. Ngoi k nng vn hnh, v sinh cc thit b c
giao, nhn vin vn hnh phi c hun luyn cc k nng lin quan n sn phm v bn thnh phm
ca tng quy trnh sn xut c th.
Nhn vin k thut. Ngoi kin thc chuyn mn v c in, cc nhn vin k thut phc v trong
dy chuyn sn xut phi c hun luyn cc k nng tng t nh nhn vin vn hnh my.
Gim st dy chuyn sn xut. Ngi gim st dy chuyn sn xut thuc vin nn phi l ngi
c hun luyn thun thc, ng thi c kinh nghim v hiu bit su sc v quy trnh sn xut, nu
c th ngi gim st nn c nhng k nng nht nh v vn hnh v bo tr cc thit b dng trong sn
xut. K nng thit lp k hoch sn xut, lp d tr nguyn ph liu v vn hnh quy trnh sn xut
cho ra sn phm t cht lng theo nh d kin l nhng yu cu cn thit i vi ngi gim st
quy trnh sn xut.
10.4. My dp vin
10.4.1. My dp vin tm sai
My ch c mt b chy ci nn cn c gi l my dp vin n chy. Lc nn t my dp vin
tm sai l do chy trn di chuyn trn mt h thng cam lch tm. My dp vin tm sai c lc nn ln
nn rt thun li trong trng hp dp vin c khi lng ln (vin nhai, vin si bt, vin pha dung
dch dng ngoi) hoc sn xut vin nn c thnh phn l dc liu.

Hnh 10.8. Chu trnh hot ng ca my dp vin tm sai
(1) Phu tip liu np cm vo ci; (2) Phu tip liu li ra sau gt ht tha;
(3) Nn vin; (4) Chy di a vin ln mt ci;
(5) Phu tip liu i ti y vin ra v np ht cho chu k tip theo

Hnh 10.9. B chy ci vi nhiu u dp
Do my ch c mt b ci chy nn cng sut rt thp, c th khc phc bng cch dng b ci chy
c nhiu u dp c th dp nhiu vin trong mt chu trnh. Lc nn vin ch yu l do chy trn,
nn vin cng hn mt trn. Ngoi ra my cn c nhc im l gy ting n khi vn hnh v bay bi
nhiu khi dp vin.
10.4.2. My dp vin xoay trn
Chu trnh nn vin trn my xoay trn gm cc giai on sau:
Ht cm t phu vo khung phn phi cm. Khung phn phi cm gm nhiu ngn ni lin
nhau tri ht cm trn mt din tch rng cho cc ci c thi gian nhn cm. Ti thi im ny,
cam di dn chy di tt xung y nhn cm vo bung nn.
Chy di v cm di chuyn n v tr cam kim sot iu chnh v tr ca chy di trong ci,
thanh gt gn trn khung phn phi cm s gt bng mt khi cm trong bung nn c mt khi
lng ht nht nh.
Sau khi iu chnh khi lng cm trong ci, chy di di chuyn qua khi cam kim sot, chy
di theo cam dn h xung thp.
Chy di di chuyn n trc nn di, chy trn cng di chuyn n trc nn trn p khi ht
trong ci. Lc nn c iu chnh bng cch thay i khong cch ti hn gia hai u chy trong ci
khi c hai u chy u v tr ca nh nn. Trc nn trn thng c c nh, trc nn di c th
iu chnh xc lp cao ca chy di.
Sau khi nn, chy trn c rt ln theo cam dn, chy di i ln theo cam dn a vin ln
ngang bng mt ci, v tr vin trn mt ci c iu chnh bng nm y vin. Vin c gt ra khi
my bng mt thanh gt gn c nh pha trc khung phn phi cm.

Hnh 10.10. S cc giai on nn vin trn my xoay trn
Mt vi my xoay trn c th c thit k cho 23 chu trnh nn ng vi mt vng quay ca
mm mang ci bng cch thm phu tip liu, khung phn phi cm, cam dn hng v trc nn.
Cc my khc nhau c th c cng sut khc nhau, cng sut (vin/ n v thi gian) ph thuc vo
s lng chy ci, s trm nn v tc quay ca my.
u im ca my dp vin xoay trn:
Cng sut ln.
My chy m, t bay bi.
C th dp vin nhiu lp.
C th dp vin bao bt (vin c nhn).
10.4.3. Ci chy cho my dp vin
Ci v chy l b phn xc nh hnh dng, kch thc v cc du hiu nhn dng ca vin.
Mi b chy gm: chy trn, chy di, ci.
Trn my tm sai, phn thn chy c gn c nh trn my, phn u dp c thit k khc
nhau tu theo kch thc v kiu dng vin.
Trn my dp vin quay trn, chy c cu to gm:
u chy phng tip xc vi trc nn, c mt cnh vt trn tip xc vi cam dn hng.
C chy trn c ng knh nh hn u chy.
Thn chy hnh tr, trn thn c cc cht nh v chuyn ng ca thn chy trong trng hp dp
vin khng phi l hnh trn hoc mt thn chy mang nhiu u dp.
u dp c th c ch to lin hoc ri vi thn chy ty theo hnh dng kch c ca vin yu
cu. Mt thn chy c th mang mt hoc nhiu u dp. Chiu di u dp ca chy di di hn ca
chy trn.
Khi vin c hnh dng khng phi hnh tr trn, thn chy trn phi c lp nh v bng cht then,
m bo chy ch c chuyn ng trt tnh tin ln xung m khng c quay trn.
Khi lp chy nh v, phi lp chy trn trc xc nh v tr ca ci. Chy di lun lun nm
trong ci.

Hnh 10.11. M hnh cc ci chy v cc mu vin tng ng

Hnh 10.12. B ci chy c then nh v
10.5. Vai tr ca ht trong qu trnh sn xut vin nn
Xt ht l mt quy trnh cng ngh nhm lin kt cc tiu phn rn li vi nhau thnh nhng khi
kt t c kch thc tng i ng nht trong khong 0,1 2,0mm, trong sn xut vin nn thng
dng ht c kch thc trong khong 0,5 1,5mm.
S xt ht nhm cc mc ch chnh l tng lu tnh v kh nng chu nn ca khi bt, nh vy s
gip cho vin c khi lng ng nht v c bn c hc t tiu chun. S xt ht cn gip trnh
c s phn lp ca khi bt cc giai on tip theo sau khi trn vi dc cht, gim bay bi v
trnh c nhim cho trong qu trnh sn xut vin nn.
Trc y, giai on sn xut ht cha c quan tm nhiu, cc nh sn xut ch quan tm n cht
lng ca vin hn l cht lng ca ht, thc ra cht lng ca vin lun lun ph thuc vo cht
lng ca ht. Ngy nay, s kim tra tiu chun cht lng ca ht v cc kim tra kim sot trong qu
trnh to ht phi c thc hin m bo quy trnh sn xut lun lun n nh. Cht lng ca ht
nh hng n nhiu ch tiu ca vin nn nh thi gian r, ho tan, cng, mi mn. Nu cht
lng ht khng n nh, s mt rt nhiu thi gian x l cc vn ny sinh trong dy chuyn sn
xut. Thnh phn cng thc v quy trnh xt ht khc nhau s cho ht c nhng tnh cht khc nhau.
10.5.1. Kch thc v hnh dng ht
Kch thc v hnh dng c nh hng trc tip n khi lng trung bnh ca vin nn. Ht cng
ln v c dng cng gn hnh cu th lu tnh cng cao. Tuy nhin ht qu ln s r kh, nn lm vin
kh r.
10.5.2. Din tch b mt
Din tch b mt ca ht gi vai tr quan trng trong trng hp dc cht khng tan hoc t tan
trong nc. Trong nhng trng hp ny, c ht v c bit l din tch b mt ca ht c nh hng
ng k ti tc ho tan.
10.5.3. T trng
T trng nh hng n h s nn, xp ca vin, thi gian r, phng thch dc cht v hnh
dng cm quan ca vin.
Ht c t trng ln, th cht cng rn cn c lc nn ln c th lin kt v bin dng khi to
thnh vin. Tuy nhin lc nn cao s to vin c thi gian tan r chm v kh phng thch dc cht. C
nhng trng hp vin r ngay nhng ht khng th r c phng thch hot cht. Ht chc cng t
b mi mn, ma st trong qu trnh nn dp cao. T trng biu kin ca ht c xc nh theo phng
trnh:

M Khi lng ca ht; V
b
Th tch biu kin ca ht.
Th tch chim ch ca khi ht c th xc nh bng ng ong
c chia vch: mt mu th c cn khi lng chnh xc, c
cho vo ng ong, sau ng c g nh cho n khi khng ghi
nhn c s gim th tch na. Trong trng hp g th cng phi
chun ho cch g, hoc c th dng thit b xc nh t trng biu
kin thit k theo m hnh sau:
H s nn C (%)
10.5.4. bn v xp
bn v xp ca ht l yu t quan trng nh hng n:
Phn b c ht.
Kh nng nn ht dnh vo nhau: ht qu cng s kh dp vin.
10.5.5. Tnh chy ( trn chy lu tnh)
c tnh chy ca dng tiu phn cht rn chu tc ng lc ma st, sc cng b mt, lc c hc gy
ra bi s ci vo nhau gia cc ht c gc cnh khc nhau, lc tnh in, lc dnh hoc lc Van der
Waals
Tt c cc lc ny c th nh hng ln tnh cht chy ca ht. Chng cn c th nh hng ln cc
tnh cht khc ca ht:
C ht v phn b c ht.
Hnh dng ht.
Kt cu ht hoc th ca ht.
Nng lng b mt.
Din tch b mt.
Vi bt mn ( 150m) lc ma st v lc Van der Waals chim u th.
Vi ht ( 150m) c sn xut bng phng php xt ht t, lc ma st thng chim u th
hn lc Van Der Waals.
Khi kch thc ca ht tng ln cc tnh cht vt l, tnh cht c hc v s sp xp ca chng thay
i theo.

b
T trng biu kin trc khi g.

T trng biu kin sau khi g.

H s nn ln th hin tnh chy ca ht km v ngc li.

Hnh 10.13. M hnh nguyn tc
hot ng ca thit b xc nh
th tch biu kin
10.5.6. Gc ngh
Phng php xc nh gc ngh l phng php n gin nh gi lu tnh mt cch gin tip.
thu c kt qu tng i n nh cn chun ho thao tc ht. Ht c qua mt phu gn c
nh. o ng knh v chiu cao ca khi ht hnh chp t tnh c gc

Nu: 30
o
: Ht chy tt.

40
o
: Ht chy km.

10.6. Cc phng php sn xut vin nn
10.6.1. Sn xut vin nn bng phng php dp trc tip (dp thng)
Phng php dp trc tip trc y c hiu l dp n cht, do ch c nhng dc cht c
tnh trn chy v tnh chu nn tt nh KBr, KCl, NaCl c s dng dp trc tip. Trn thc t,
cc trng hp dp n cht rt kh p dng v vin c th kh r, nn khng cho tc dng iu tr tt.
Ngoi ra, c rt nhiu dc cht c liu iu tr rt thp nn kh c th iu ch c vin nn m
khng thm t dc.
Ngy nay, phng php dp trc tip c hiu l phng php dp vin khng qua giai on xt
ht.
a) u im ca phng php
Sn xut vin nn bng phng php dp thng ch cn c hai thit b cn bn l thit b trn kh v
my dp vin. Theo phng php ny c th tit kim c chi ph u t trang thit b v c s vt
cht, quy trnh sn xut nhanh hn v tit kim c nng lng hn khi sn xut bng cc phng
php xt ht. So vi vin c iu ch bng phng php xt ht t, tc phng thch dc cht ca
vin nn iu ch bng phng php dp thng t thay i theo thi gian bo qun.
Phng php ny cng thch hp cho nhng dc cht d b ph hu bi nhit.
b) Cc vn cn lu trong phng php dp thng
Lu tnh ca khi bt v kh nng kt dnh (tnh chu nn) ca dc cht v t dc l hai yu t
phi c quan tm hng u trong phng php dp thng. Cc t dc dng dp thng phi l loi t
dc a chc nng.
Khi bt dng trong phng php dp thng c th b tch lp cc cng on sau khi trn, dn n
khng ng u hm lng, nht l trong trng hp vin c hm lng nh. ngn nga hin tng
tch lp c th chn t dc c t trng v kch thc gn vi t trng v kch thc ca dc cht,
iu ny hu nh kh c th thc hin c trong trng hp vin c hm lng thp v dc cht phi
c nghin mn m bo dc cht phn b u trong khi bt giai on trn kh.
Kch thc tiu phn dc cht. tng tc ho tan v tng sinh kh dng ca thuc vin nn,
nhiu dc cht c sn xut di dng bt siu mn, cc loai dc cht ny c tnh chu nn v lu
tnh rt km do ma st gia cc tiu phn ln.
Tuy nhin, dc cht c nghin mn li gip cho s trn u d dng hn trong trng hp iu
ch cc vin c hm lng nh.
Rt kh phi hp ng u cc cht mu trong phng php dp trc tip, khc phc c th dng
mu khng tan c nghin n dng siu mn.
Do c nhiu cht rn di dng ht mn nn thng phi dng nhiu t dc trn hn cc phng
php xt ht. Cn xc nh c th loi t dc trn, t l s dng v thi gian trn. S dng t t dc
trn s lm vin c sai s hm lng v khi lng, nhiu t dc trn lm vin c khuynh hung mm.
Ch nn trn trong thi gian khong 3 5 pht v nn trn sau khi trn tt c cc thnh phn khc.
Dc cht dp thng. Cc dc cht dp thng c sn xut nhm ci thin lu tnh v tnh chu
nn ca dc cht. Cc dc cht dp thng c cung cp di hai dng:
Dng kt tinh tinh th ln. Mt vi dc cht c th c kt tinh dng tinh th ln v c th dng
dp thng nh Vitamin C, Aspirin
Dc cht c xt ht sn. Dc cht kt tinh dng Otinh th ln c khuynh hng dn nn tnh
chu nn khng cao, khc phc mt s nh sn xut cung cp nguyn liu di dng c xt ht sn
nh:
C 90 (Roche): Vitamin C xt ht sn vi 10% tinh bt.
C 95 (Roche): Vitamin C xt ht sn vi 5% methyl cellulose.
C 97 (Takeda): Vitamin C xt ht sn ch cha khong 3% t dc.
Acetaminophen dp thng (Cornpap): hm lng 90%, c tnh chu nn v lu tnh cao.
Ibuprofen dp thng (Mallinckrodt): hm lng 63%.
T dc dng trong phng php dp thng phi l loi t dc a chc nng, t nht phi bao gm
chc nng chnh l n, dnh, r... mt s t dc dp thng cn c thm chc nng trn nh tinh bt
1500.

Hnh 10.14. Lactose monohydrat dng kt tinh
dng cho cc phng php xt ht

Hnh 10.15. Lactose phun sy dng cho
phng php dp thng
Bng 10.2. Mt s t dc dp thng thng dng
10.6.2. Sn xut vin nn bng phng php xt ht kh
Phng php xt ht kh l phng php iu ch ht bng cch nn dc cht v t dc thnh
vin hoc p thnh phin, sau nghin vin hoc phin thu c ht.
Phng php xt ht kh c p dng cho dc cht d hng bi m hoc nhit hoc c hai yu t
ny; cng p dng trong trng hp vin cha hm lng dc cht cao kh p dng phng php dp
trc tip.
Ht sn xut bng phng php xt ht kh thng cng chc, hnh dng khng ng u v c
nhiu gc cnh.
Quy trnh sn xut ht gm cc cng on:
Dc cht c trn vi t dc dnh dng rn.
Hn hp bt c nn thnh vin to tm thi, hoc p bng my p.
Nghin vin tm thi hoc khi rn n kch thc thch hp, thm t dc trn bng v dp thnh
vin.
Ht iu ch bng cch nn vin tm thi hay bng my p u khng c qu cng, lc nn tm
thi phi nh hn lc nn chnh thc ht cn c th bin dng c trong giai on dp chnh thc.
10.6.3. Sn xut vin nn bng phng php xt ht t
Trong sn xut vin bng phng php xt ht t, s lin kt gia cc tiu phn rn to thnh
ht kt t l do tc ng ca mt pha lng c gi l t dc dnh lng.
a) u im ca phng php
Kh nng kt dnh v tnh chu nn ca khi bt t n mc ti u, quy trnh xt ht t to ra ht
c kch thc ln v xp cao, cc ht ny s v ra trong qu trnh nn nn to c nhng b mt
mi gip vin dnh chc hn ngay c khi nn vi lc nn thp.
Lng t dc dnh cn thit t hn trong phng php xt ht kh nhng s lin kt gia cc tiu
Tn thng dng Tn thng mi
Lactose DCL, Tablettose, Fas Flo Lactose
Avicel 101, 102 Emcocel
Calci sulfat Delaflo
Saccharose Dipac
Dicalci phosphat Di Tab, Emcompress
Sorbitol Sorbitol 1162, 834
Tricalciphosphat Tritab
Lactose phun sy

phn cht rn rt tt.
S phn b dc cht trong khi ht ng nht nn rt thch hp cho sn phm c hm lng hot
cht thp, s phn b cc cht mu cng ng u hn.
Tc ho tan ca dc cht kh tan c th c ci thin tt hn nu chn c dung mi v t
dc dnh thch hp.
Cc tnh cht vt l ca vin nh mi mn, thi gian r thng n nh hn so vi vin dp
thng hoc xt ht kh.
b) Nhc im
Phng php xt ht t l mt quy trnh nhiu cng on nn cn c nhiu thit b v din tch
thc hin tt c cc cng on ca quy trnh.
Thi gian thc hin quy trnh thng di, nht l giai on to ht v sy ht.
Kh nng nhim cho v hao ht sn phm c th xy ra do phi di chuyn bn thnh phm t khu
vc ny sang khu vc khc.
c th sn xut c ht c cht lng cao, cn phi thm nh thn trng mi cng on ca
quy trnh sn xut ht. Cht lng ca ht ph thuc vo nhiu yu t:
tan ca hn hp bt trc khi xt ht.
Kch thc v hnh dng ca cc tiu phn dc cht v t dc.
nht v kh nng kt dnh ca t dc dnh.

Hnh 10.16. S sn xut vin theo phng php xt ht t
S xt ht t c th c thc hin theo 2 cch:
Trn t dc dnh dng rn vo khi dc cht v cc t dc khc (giai on trn kh), sau
phun dung mi to thnh khi m.
Phi hp t dc dnh vi dung mi to thnh t dc dnh lng dng dung dch, hn dch hoc
khi nho, dng t dc dnh lng lm m khi bt.
c) Cc thit b dng trong quy trnh xt ht t kinh in
Giai on trn kh
giai on trn kh c th dng my trn lp phng, my trn hnh V, my trn inh c v tn.
Giai on trn t
Cc my dng trn t dc dnh vo khi bt phi c kh nng trn mnh nh my trn hnh
tinh, my trn Z.
Giai on xt ht: Khi m c th c to ht bng my xt ht u a hoc my p n
(extruder).
Nguyn l hot ng ca my xt ht u a l p khi bt m qua mt li to thnh cc ht c
kch thc tng i bng nhau v c xp cao.
My p n to ra cc si cm ngn, do lc p mnh nn si cm t c xp, ht to thnh sau giai
on sy s cng hn ht c iu ch bng my xt ht u a.
Giai on sy
Ht c th c sy bng t sy c dng kh i lu hoc bng my sy tng si. Hin nay my sy

Hnh 10.17. My trn hnh V

Hnh 10.18. My trn inh c v tn

Hnh 10.19. My trn hnh tinh

Hnh 10.20. Nguyn tc hot ng ca my p n
tng si c ng dng nhiu do kh nng sy cao, gim c thi gian sy nn c th tng nng
sut v hn ch c h hng dc cht.
Giai on ry sa ht
Ht sau khi sy c lm nh bng my xt ht u a n kch thc cn thit sau thm t dc
trn bng. Thi gian trn t dc khng nn di qu trnh ht b v.
Xt ht t bng my trn v xt ht cao tc
My trn v xt ht cao tc (high speed mixer = high speed granulator) c th thc hin c c ba
cng on ca quy trnh xt ht t l trn kh, trn t v to ht. Thit b gm mt thng trn bng
thp, y thng trn c mt cnh trn c chc nng trn kh v trn t. Khi trn t, t dc dnh
c cho vo bng cch phun hoc qua mt ca m trn np.
Trn thnh thng trn c mt cnh to ht quay vi tc cao, c chc nng ct khi m thnh cc
ht c kch thc khng u nhau (trong khong 1,4 2,4 mm). Khi xt ht bng my xt ht cao tc,
lng cht lng cn thit t hn so vi quy trnh xt ht kinh in, nn cn phi tng nng t dc
dnh.
Ht iu ch bng my to ht cao tc thng c xp cao hn cc phng php kinh in. Trong
sn xut bng my to ht cao tc, thi gian trn kh cn c kim sot nghim ngt, nu thi gian
trn qu lu, kch thc tiu phn ca dc cht v t dc thay i c th nh hng n phng
thch dc cht ca vin sau ny.
d) Xt ht bng my tng si
Trong k thut to ht bng my to ht tng si, s kt t ca cc tiu phn v s sy xy ra ng
thi trong cng mt thit b v thi gian thc hin rt nhanh. Ht c to ra bng my to ht tng si
thng c kch thc rt ng u nn khng cn qua giai on ry sa ht. Ht c xp v tnh chu
nn rt cao. Vin c sn xut bng my to ht tng si thng d r v d ho tan.

Hnh 10.21. My to ht cao tc

Hnh 10.22. Thng trn ca my to ht cao tc

Hnh 10.23. Nguyn tc hot ng ca my to ht tng si
Bng phng php to ht tng si, kch thc ca ht c kim sot d dng nn c th khng cn
phi qua giai on sa ht.
10.7. Kim tra kim sot trong qu trnh sn xut vin nn
Cng vi nhng quy nh ca GMP, s thm nh quy trnh sn xut vin nn phi c thc hin
nhm m bo quy trnh sn xut n nh, m bo thnh phm v cc bn thnh phm ca tng giai
on sn xut t cc tiu chun cht lng nh d kin. S thm nh quy trnh sn xut vin nn
gm cc mc tiu chnh l thit lp qun l h s, cc kim tra kim sot trong qu trnh sn xut v
kim nghim thnh phm.
S thm nh quy trnh phi c cp n ngay t giai on nghin cu xy dng cng thc (giai
on RvD) v phi c thc hin tt giai on sn xut trn quy m cng nghip.
Theo FDA, s m bo cht lng ca sn phm bt ngun t cc kim sot cht lng thn trng
v c h thng tt c cc giai on ch yu ca quy trnh sn xut bao gm: la chn nguyn liu, xy
dng v thit k m hnh sn xut, thc hin cc kim tra kim sot trong qu trnh sn xut v kim
tra cht lng sn phm.
Trc khi dp vin, nhn vin m bo cht lng phi tin hnh kim tra tnh trng v sinh v nhn
ca cc thng nguyn liu, cc thit b dng trong dy chuyn sn xut phi trong tnh trng v sinh sch
s v c phiu ghi tn sn phm, hm lung v s l ca sn phm s tin hnh.
Khi bt u dp vin tin hnh hiu chnh my c th dp c vin t nhng tiu chun cht
lng nh d kin trn cc ch tiu cm quan, khi lng trung bnh, cng, mi mn v thi
gian r. Cc vin c dp trong giai on hiu chnh my phi c ring v tiu hu.
Trong giai on dp vin cc ch tiu vt l ca vin nh hnh dng cm quan, mu, mi, dy,
ng knh, mi mn, cng, sai s khi lng v thi gian r s thng xuyn c kim tra v
ghi thnh h s. Cc th nghim kim tra trong qu trnh dp vin nhm pht hin nhng s c xy ra
trong qu trnh dp vin. Nguyn nhn ca nhng s c thng gp l do tnh trng ca ht cha t nh
s trn ca cc thnh phn cha ng nht, t l ht mn qu nhiu, lu tnh km, nhim cho, t dc
trn cha ph hp.
Cc mu s c ly trong qu trnh dp vin, c kim tra v quy trnh sn xut s c hiu
chnh cho n khi cho ra sn phm t yu cu. Trong vi trng hp nh sai s khi lng hoc thi
gian r khng t, th phi loi b tt c nhng vin dp trc khi pht hin v sa cha. S lng
mu mi ln ly tu thuc vo c l v tnh cht ca sn phm. Nu my c nhiu ca ra thuc, th cc
vin ra t mt ca c xem nh mt my c lp v c kim tra ring.
Thi im ly mu tu thuc vo c l, thng thng trong sn xut c th ly mu nh sau:
Kim tra khi bt u dp vin: cm quan, khi lng vin, dy, ng knh, cng, mi
mn v thi gian r.
Kim tra cm quan cch mi gi.
Kim tra mi mn, cng, dy, ng knh, khi lng trung bnh v thi gian r cch
mi 2 gi.
Kim tra khi kt thc dp vin: cm quan, khi lng vin, dy, ng knh, cng, mi
mn v thi gian r.
ng nht v cm quan vin nn c th c nh gi bng cch quan st, mu ca vin c th
c nh gi bng cch so vi vin chun.
Sai s dy cho php thng c p dng l 5%. dy ca vin nn thng thay i t l
sang l do xp ca ht khc nhau, tc my dp khc nhau hoc lc nn trn vin khc nhau.
10.8. Cc s c thng gp khi dp vin nn
10.8.1. Chnh lch khi lng vin
Khi lng vin c xc nh bng lng ht trong ci trc khi nn. Do , nu ci khng c
np y c th lm vin khng khi lng. Tuy ci c mt th tch nht nh, nhng vn c th xy
ra hin tng vin chnh lch khi lng nu ht c phn b kch thc rng.
Kch thc ht cn ph hp vi ng knh ca ci, nguyn tc chung l vin ln dng ht ln v
vin nh dng ht nh. S chy khng u ca ht l mt nguyn nhn gy ra chnh lch khi lng.
cao ca chy di khng bng nhau cng l mt nguyn nhn lm cho khi lng vin khng
ng nht do lng ht np vo ci khng ng nht.
Khc phc:
Thm t dc trn.
Chn li ht, loi b bt ht qu mn v qu to.
Sa li chy.
10.8.2. Vin dnh chy
Vin dnh chy hoc my kh y vin ra do nguyn nhn chnh l thiu t dc trn, c th khc
phc bng cch:
Thm t dc trn.
Dng t dc trn hu hiu hn (v d Aerosil).
Ry t dc trn qua ry mn trc v trn t dc trn vi mt t bt mn trc khi trn vo khi
ht.
Gim kch thc ca ht.
Tng hm m ca khi ht.
Cc t dc trn bng nng chy nhit cao cng l mt nguyn nhn gy dnh vin vo chy,
trong trng hp ny phng dp vin phi c nhit thp v nn vn hnh my tc chm.
10.8.3. Vin t chm hoc bong mt
t chm l hin tng phn trn ca vin b t ri ra ngay sau khi dp. Nguyn nhn thng do
khi khng kh trong ht b nn mnh nhng khng thot ra c v to thnh mt lp m khng kh,
lp m ny trng n nhanh thi k gii nn. Hin tng ny thng gp khi khi ht c qu nhiu
bt mn hoc khong cch gia chy v ci qu nh (chy v ci mi a vo s dng).
Cc nguyn nhn khc c th gy nn hin tng t chm l do thiu t dc trn hoc hm m
ca ht qu cao.
Bong mt l hin tng mt phn trn ca vin b tch ri ra, s bong mt c th xy ra do cc
nguyn nhn ging nh trng hp t chm. khc phc s c t chm c th:
Thay i quy trnh xt ht.
Tng lng t dc dnh.
Thm t dc dnh kh nh tinh bt tin gelatin ho, PVP, gm arabic
Thay i t l (tng hoc gim) hoc thay t dc trn bng.
10.8.4. Vin m cnh, nt
Vin m cnh c th do chy qu mn nn vin b m quanh g vin (cnh vin khng sc) hoc do
vin cha ln khi mt ci b ht ra khi my (do phu tip liu ca my dp vin tm sai hoc thanh
gt trn my xoay trn).
Nt vin l hin tng vin b nt ngang trn b mt vin, nguyn nhn thng do vin dn n
mnh thi k gii nn.
Cc bin php sau y c th p dng trnh hin tng nt vin hoc m cnh:
Sa li mt chy.
Gim lng bt mn trong khi ht.
Gim kch thc ht.
Thay chy b mn qu nhiu.
Thm t dc dnh dng kh.

Hnh 10.24. Vin m cnh (tri) v vin t chm (phi)
10.8.5. Dnh chy
Dnh chy l hin tng mt phn ht t vin b tch ra khi vin v dnh cht vo chy khi x nn.
C th gy hin tng dnh vin l do mt chy b r, t dc dnh thiu, hm m ca ht qu cao,
cc thnh phn ca cm c nhit nng chy thp. C th c khc phc bng cch sy ht k hn
hoc thm t dc ht (nhm hydroxyd, cellulose vi tinh th), sa li mt chy hoc nh bng mt
chy bng du parafin.

TI LIU THAM KHO
1. Robert A. Nash, The essentials of process validation, in Pharmaceutical dosage forms: Tablets,
Vol. 3, Marcel Dekker, 1990, Pg. 417.
2. Roger E.Gordon et al., Granulation technology and tablet characterizaion, in Pharmaceutical
dosage forms: Tablets, Vol. 2, Marcel Dekker, 1990, pp. 245254.
3. Deodall A.Wadke et al., Preformulation testing, in Pharmaceutical dosage forms: Tablets, Vol. 1,
Marcel Dekker, 1990, pp. 1 157
4. Fred J.Banderlin, Compressed tablet by wet granulation, in Pharmaceutical dosage forms:
Tablets, Vol. 1, Marcel Dekker, 1990, pp. 131151.
5. Ralp F.Shangraw, Compressed tablet by direct compression, in Pharmaceutical dosage forms:
Tablets, Vol. 1, Marcel Dekker, 1990, 195203.
6. Mary J. Kottke, Edward M.Rudnic. Tablet dosage form, in Modern Pharmaceutics, Fourth
Edition, Marcel Dekker 2002, pp. 287234.
7. Robert J.Connolly, Frank A. Berstler, David Coffin Beach, Tablets Production, in
Pharmaceutical dosage forms: Tablets, Vol. 3, Marcel Dekker, 1990, Pg. 369415.

CU HI LNG GI * CHN CU TR LI NG NHT
1. Vin nn c khi lng trung bnh l 120mg, s vin cn phi ly xc nh mi mn nn l:
a) 10 vin; b) 20 vin;
c) 30 vin; d) 40 vin; e) 50 vin.
2. Thi gian r trung bnh ca vin nn khng bao:
a) Ln hn hoc bng 15 pht; b) Nh hn hoc bng 15 pht;
c) 15 pht; d) 30 pht.
3. Dng thuc vin nn khng cn th ho tan:
a) Vin cho tc dng ti ch trong ng tiu ho;
b) Vin cha dc cht rt d tan;
c) Vin bao tan trong rut;
d) Vin phng thch dc cht ko di;
e) Tt c cc dng trn u khng cn th.
4. Tnh cht no ca dc cht nh hng nhiu nht n sinh kh dng ca thuc
a) tinh khit; b) Hm m;
c) tan; d) Kch thc ht v phn b kch thc ht;
e) Mu, mi, v.
5. Bin php no tt nht nn p dng lm tng sinh kh dng ca thuc vin nn cha dc cht
kh tan:
a) Dng t dc siu r;
b) Nghin dc cht n dng siu mn;
c) Nn vin n cng va phi;
d) Chia lng t dc r thnh hai phn khi phi hp;
e) Khng c bin php no ph hp.
6. Nguyn nhn c th gy nn cng khng ng u ca cc vin trong cng mt l:
a) Lng t c dnh s dng qu nhiu;
b) Phn tn t dc dnh khng u;
c) Sau khi ti t dc dnh, thi gian nho trn qu di;
d) T dc dnh c kh nng kt dnh qu cao;
e) Khng cu no ng.
7. Tnh cht no ca ht cn thit cho vin c cng cao:
a) Phn b kch thc ht khng qu rng;
b) Ht phi cng;
c) Ht phi c th bin dng c khi c mt lc nn tc ng;
d) Ht c m trong phm vi cho php.
8. Tnh cht no ca ht gip cho vin t ng u khi lng
b) Ht phi cng;
d. Ht c m trong phm vi cho php.
9. Tnh cht no ca ht gip cho vin t mi mn
b) Ht phi cng;
d. Ht c m ph hp.
10. Ht iu ch bng phng php no c xp cao nht
a) p khi m qua ry, sy, sa ht.
b) Xt ht trn my xt ht cao tc;
c) To ht bng my tng si;
d) Tt c cc phng php trn.
11. Nng sut (vin/pht) ca my dp vin xoay trn ph thuc vo:
a) Cu to ca b ci chy v s lng ci chy;
b) S lng ci chy v tc quay ca mm mang chy ci;
c) S lng ci chy v khi lng ca vin;
d) Khi lng ca vin nn v in p;
e) Tt c cc yu t trn.
12. Phn bit chy trn chy di bng:
a) Hnh dng u dp; b) Hnh dng ton chy;
c) Chiu di chy; d) Chiu di u dp.
13. Phng php dp vin trc tip:
a) Ch p dng dp vin n cht: KCl, NaCl, KBr;
b) Ch dnh cho nhng vin c hm lng hot cht ln;
c) p dng c vi nhng vin c hm lng hot cht trung bnh v nh kt hp vi t dc dp
thng;
d) Ch thch hp cho nhng hot cht c tinh th hnh kim.
14. Trong xt ht t iu kin sy cm l:
a) 100
o
C;

b) Sy n khi lng khng i;
c) Sy va phi, nhit 50 60
o
C v thi gian sy tu tng loi sn phm;

d) Sy 40
o
C trong 5 gi.

15. Tnh cht no ca ht lm vin dnh chy
a) Ht qu cng;
b) Ht c kch thc qu nh;
c) Ht thiu t dc trn;
d) Ht c lu tnh km.

Bi 11
CNG NGH BO CH VIN BAO

11.1. Khi nim v vin bao
Bao vin l qu trnh bi p ln vin nhn cc cht bao thch hp nh ng, cc polyme hoc cc
t dc khc, i khi trong lp bao c th cha dc cht.
Bao vin nn cng on cui cng trong cc quy trnh sn xut vin nn, thng l cng on b
sung nng cao cht lng ca sn phm, tuy nhin trong nhiu trng hp, cng on ny quyt nh
cht lng ca sn phm, v d nh trong trng hp vin bao tan trong rut hoc vin tc dng ko di.
Trong cng nghip dc phm bao vin nhm cc mc ch sau:
Bo v dc cht khi cc yu t bt li ca mi trng xung quanh nh m, khng kh, nh
sng nn lm tng n nh ca dc cht c trong vin nn.
Che giu mi v kh chu ca dc cht.
Gip bnh nhn d nut vin hn.
Gip phn bit c cc sn phm vin khc nhau qua mu sc, hnh dng.
Tng bn c hc vin c th chu c nhng tc ng vt l trong cc giai on ng gi,
vn chuyn, ng thi c th trnh c nhim cho trong sn xut, ng gi do vin mi mn, bay
bi
Ci thin hnh thc cm quan ca vin nn, c bit l trong trng hp vin nn c nhng m, vt
nh trong trng hp dp cc vin t cc cao dc liu.
Trong cc dng thuc a thnh phn, k thut bao c th gip trnh c tng k gia cc thnh
MC TIU
Nu c mc ch bao vin.
K c cc giai on ca quy trnh bao ng.
Nu c c im k thut trong sn xut vin bao ng.
Nu c cc s c k thut lin quan n vin bao ng v cch khc phc.
Chn c cc cht bao thch hp iu ch vin bao bo v, bao tan trong rut.
Nu c u, nhc im ca cc thit b dng trong bao phim vin nn.
Phn tch c cc nguyn nhn v cch khc phc cc s c lin quan n k thut bao phim
vin nn.
phn dc cht. Trong trng hp ny, cc ht cha cc dc cht khc nhau c bao trc khi
dp thnh vin hoc ng vo nang cng.
Ci thin sinh kh dng vin nn bng cch iu chnh v tr tc ng (vin bao tan trong rut),
iu chnh tc phng thch dc cht (vin phng thch ko di)
Trong cng ngh sn xut dc phm c bn k thut cn bn c s dng to mng bao l: bao
ng, bao phim, vi nang ho v bao dp.
Trong phm vi chng ny ch cp n hai k thut thng dng nht l bao ng v bao phim.
11.2. Sn xut vin bao ng
Cng ngh bao ng c s dng t rt lu trong cng nghip thc phm v l cng ngh bao
vin kinh in nht trong sn xut dc phm.
Mc d c nhiu n lc nhm ci tin v t ng ho thit b, tuy nhin cht lng vin bao
ng vn ph thuc rt ln vo tay ngh v s kho lo ca ngi thc hin quy trnh bao, nn nhiu
nh sn xut vn xem bao ng l mt ngh thut hn l mt k thut.
Vi s pht trin mnh m ca k thut bao phim, bao ng ngy cng t c quan tm nhng
nhiu nh sn xut trn th gii vn duy tr vin bao ng v nhiu l do:
Bao ng s dng cc nguyn liu r tin, d kim v cht lng n nh.
Thit b n gin, d lp t, d vn hnh.
Quy trnh bao ng thng khng qu phc tp v khng phi kim tra cht ch cc thng s
nh trong quy trnh bao phim.
Tuy nhin quy trnh bao ng c vi nhc im:
Kch thc v khi lng ca vin c th tng n 50100% nn khng ph hp i vi vin nhn
c hm lng hot cht cao hoc c khi lng ln.
Lp bao ng kh dn nn d b m nu bo qun v vn chuyn khng thch hp.
Quy trnh bao kh t ng ho, ph thuc phn ln vo k nng ca ngi thc hin quy trnh
bao.
11.2.1. Nguyn liu dng sn xut vin bao ng
Cc loi ng:
ng saccharose l nguyn liu chnh trong sn xut vin bao ng. ng saccharose rt t ht
m v l nguyn liu rt d tan trong nc, cho dung dch c nng rt cao. tan ca ng
saccharose tng theo nhit . nht ca ng gim nhit cao. Sir ng nng t 65%
hoc thp hn khng b kt tinh nhit thng. Dung dch ng nng trong khong 50 60%
( nht thp hn 2 poise) c xem l ph hp nht khi bao bng sir ngui.
ng saccharose c th b thu phn thnh cc ng nghch chuyn l glucose v fructose. S
thy phn xy ra nhanh khi c cc iu kin thun li sau:
Nhit cao.
pH nh hn 6,0.
S hin din ca cc cation ho tr 2 hoc 3.
ng nghch chuyn l nguyn nhn lm vin khng kh trong qu trnh bao ng.
S kt tinh ca ng. ng c th b kt tinh khi dung dch ng t n trng thi qu bo ho.
H s kt tinh c biu th theo cng thc:

i vi ng saccharose, s kt tinh bt u xy ra khi Cs > 1,23; trong trng hp c ht mi, s
kt tinh c th xy ra vi Cs thp hn (khong 1,06). Trong k thut bao ng, iu quan trng nht l
ng phi khng c kt tinh trc khi vo khi vin, nhng phi c kt tinh nhanh v hon
ton sau khi c phn tn u trn ton b khi vin. S kt tinh ca ng t sir c th chm nu c
s hin din ca ng khc nh glucose, lactose, ng nghch chuyn, oligosaccharid.
Lactose. Do tan km, nn lactose t c dng ring r m thng phi hp vi ng
saccharose.
Maltitol. Maltitol l mt ng bn tng hp c th dng bao vin nn v c dng di dng
dung dch. Maltitol tan rt tt trong nc, c th t n nng 77% 20
o
C. Dung dch maltitol c
nht thp nn c th thc hin bao ng bng phng php phun.
Maltitol c ngt gn bng vi ng saccharose (khong 95% so vi sir), khng c tc dng
gy x v ch c khong 50% b thu phn bi dch tiu ho nn y l dng vin bao thch hp vi
bnh nhn king ng.
Sorbitol. Sorbitol c th tan c trong nc cho dung dch c nng cao hn c ng
saccharose. Sorbitol rt ht m nn vin c khuynh hng mm v gim bn c hc sau thi gian bo
qun nn cn phi c lp bao chng m tt.
Xylitol. Xylitol c tan cao hn c ng saccharose nhit cao hn 30
o
C. Lp bao xylitol c
khuynh hng dn, c th khc phc bng cch thm 2% gm arabic. Lp bao xylitol c tnh thm m
v kh rt thp nhng tan rt nhanh khi tip xc vi dch tiu ho hoc mi trng th.
Mannitol. t c s dng trong bao ng do tan rt km, ch c th dng di dng hn dch.
T dc n: calci carbonat, talc, titan dioxyd
Cht mu.
Cht to phim: gm, gelatin, dn cht cellulose, dn cht ca acid methacrylic.
Cht chng dnh: talc.
Cht din hot: gy thm gip cho dch bao bm u vo vin nhn v gip cc tiu phn rn phn
tn tt trong dch bao.
11.2.2. Quy trnh bao ng
Quy trnh bao ng gm nhiu cng on, mi cng on c mt mc ch khc nhau:
Bao bo v (= bao cch ly)
Hu ht cc vin nn u c mt xp nht nh nn d ht m, ngoi ra vin nn thng c
thit k sao cho c th r rt nhanh trong mi trng nc, nn vin cn c cch ly bng mt lp bao
khng thm nc trnh vin b hng cc giai on bao k tip.
Lp bao bo v c th c thc hin bng phng php ti cc dung dch polyme ln b mt vin.
Cc cht bao bo v thng dng l shellac, zein, hydroxypropyl methyl cellulose (HPMC). Cc cht
ny c th c pha vi nng 15 30%.
Shellac l cht bao bo v c dng rng ri nht, nhng c kh nng polyme ho chm nn lm
vin r chm hoc ho tan chm sau thi gian bo qun. Hin tng ny c th c khc phc bng
cch dung hn hp PVPshellac.
Lp bao bo v phi tht mng khng lm vin thay i r v ho tan.
Khi dch bao bo v c thm bng cch ti, cn cho thm talc cc vin khng b dnh i
hoc dnh li thnh khi, tuy nhin nu dng nhiu bt talc cc lp bao ng cc cng on k tip s
kh dnh.
Khi cn iu ch vin bao ng tan trong rut, lp bao bo v tr thnh lp bao chc nng bng
cch s dng cc polyme khng tan trong mi trng acid nh CAP, HPMCP, PVAP, Eudragit L,
Eudragit S
Bao lt (= bao nn)
Bao lt l cng on quan trng trong quy trnh bao ng. Mc ch ca giai on ny l lm trn
cc gc cnh v vin nhn t n khi lng cn thit.
Nguyn liu dng bao lt l cc cht rn nh talc, calci carbonat, kaolin, calci sulfat, titan dioxyd..
tng kt dnh ca sir v lm cho lp bao c bn cao nn thm mt lng nh cht to
phim nh gm arabic, gelatin, cc dn cht cellulose.
giai on ny, quan trng nht l lp bao phi ph ht cc gc cnh ca vin. c th ph ht
cc gc cnh th hnh dng ca vin nhn rt quan trng, vin cng li cng d bao.
S bao lt c th c thc hin theo mt trong hai cch: thm t dc dnh v rc bt lin tc hoc
iu ch thnh hn dch cc cht rn trong t dc dnh.
Phng php thm t dc dnh bt lun phin l phng php kinh in nht nhng tng i
kh thc hin. Phng php ny i hi phi c s cn bng nht nh gia lng t dc dnh v lng
bt c thm vo. Phng php ny lm tng khi lng vin rt nhanh nhng oi hi phi c s kho
lo v kh c th t ng ho quy trnh.
Phng php bao bng hn dch cho php kim sot quy trnh d dng hn v c th c thc hin
bi nhn vin t thnh tho v c th t ng ho d dng nhng khi lng vin tng rt chm, thi
gian bao rt lu.
Bao nhn (Grossing osmoothing)
Mc ch ca giai on ny l lm cho b mt vin tht lng trc khi bao mu. Nu lp bao t
c giai on bao lt lng th giai on ny c th b qua. Ty theo nhn mong mun, lp bao
lng c th l sir hoc sir c pha thm titan dioxyd to c, hoc thm cht mu to mu nn.
Bao mu (Color coating)
Bao mu l giai on quan trng nht trong quy trnh iu ch vin bao, quyt nh hnh dng cm
quan ca vin. T dc mu c th c ho tan hoc phn tn vo trong sir.
K thut bao mu bng dung dch cc cht mu tan thng kh thc hin hn bao mu bng hn
dch, thi gian bao mu bng dung dch mu tan thng mt khong 2 3 ngy. Nu bao nhanh qu,
mu s phn tn khng ng u trn vin lm vin c m hoc c sc do s di chuyn ca cht mu
(loang mu) trong qu trnh sy. Ngoi ra, mu tan thng km bn di tc ng ca nh sng.
bao bng dung dch mu, thng phi bi tng lp mng dung dch mu vi nng mu tng
dn cho n khi t c mu mong mun. Mi t thm cht mu ch c thm mt lng nh, cho
ni quay mu bm u v sy nh trnh s loang mu. Nn dng dung dch mu c nng cht
mu thp v bao nhiu ln lp mu bm u cho n khi t n mu cn thit, i khi phi bao n
khong 50 60 lp mu.
Phng php bao bng dung dch mu c th to ra vin c b mt sng hn khi c bao bng hn
dch. Tuy nhin nu k thut bao khng tt c th xy ra cc hin tng:
Mu khng u trn mi vin: nguyn nhn l do nhit sy qu cao (hin tng loang mu)
hoc qu thp.
Mu khng u gia cc vin: do s phn b cht bao khng ng nht do s o trn khng u.
Mu khng u gia cc l do lng cht mu gia cc l khng ging nhau.
K thut bao bng hn dch cc cht mu khng tan c phn tn trong sir c u im l hn
ch c s loang mu khi sy vin, thi gian bao nhanh hn v mu khng tan t b phai hn mu tan
khi tip xc vi nh sng.
Trong phng php ny ch dng mt hn dch mu c nng duy nht trong qu trnh bao, c th
thm titan dioxyd iu chnh cng mu. ng nht ca mu c th t c sau khong 8
10 ln ti dch, sau c th thm khong 5 7 lp lm lng b mt.
u im:
S phn b mu trn vin ng nht hn so vi bao bng dung dch, khng c hin tng loang
mu.
S phn b mu gia cc l tt hn.
Gim dy ca lp bao mu.
Gim thi gian thc hin ca ton b quy trnh.
Nhc im:
Lp bao mu khng sng nh trong trng hp bao bng mu tan.
Nu bao qu nhanh s lm mt vin khng lng.
Phi lun lun m bo hn dch mu c phn b ng nht, nu khng s c hin tng mu
lm m.
a s cc mu khng tan c tnh acid, nu nu sir mu nhit qu cao ng saccharose s b
thu phn thnh ng nghch chuyn.
Bao bng (Glossing polishing)
Vin sau khi c bao mu thng c b mt khng sng, giai on nh bng gip cho mu sc
trn vin tr nn sng hn.
Cc nguyn liu dng trong giai on bao bng c th l sp ong, sp carnauba; cc cht ny c th
c pha trong dung mi hu c hoc iu ch thnh khi nho trong cn hoc dng di dng bt mn
phn tn u trong khi vin trc khi sy. Vin c th c nh bng trong ni bao vin sch hoc
ni nh bng c lt n. Trc khi nh bng vin cn c sy nh qua m loi hon ton m trong
vin.
11.2.3. c im k thut trong sn xut vin bao ng
Trong sn xut vin bao ng, dch bao c cho vo bng cch ti ln khi vin ang chuyn
ng vi mt lng c tnh ton trc, sao cho va lm t khi vin. Do sir l mt cht lng
kh bay hi, nn s phn tn ng nht cc lp bao l do cc vin c xt vo nhau khi o trn phn
phi dch bao. Trong trng hp ny khng nht thit tt c cc vin phi di chuyn qua vng ti dch.
S ng nht ca lp bao chu tc ng ca cc yu t sau:
Dch bao phi cn tn ti th lng trong mt thi gian ngn sau khi tt c cc vin c thm
t.
Lng dch bao mi ln ti phi lm t khi vin, nh vy lng dch bao phi tng dn
ph hp vi s tng khi lng vin dn dn trong quy trnh bao.
Ni bao phi c hnh dng v chuyn ng sao cho khi vin c o u, hn ch cc im cht
trong khi vin. Nu ni khng c cnh o th phi dng tay o khi vin c chuyn ng u,
nht l sau mi ln ti dch bao.
C th ci tin k thut bao ng bng cch dng sng phun dch bao, cn lu l cc git sir
phun ra khng c qu mn v dy phun qu rng s lm t ni bao nhiu hn l lm t khi vin.
H thng phun dch tt nht trong trng hp bao ng l h thng phun khng dng kh nn.
11.2.4. Thit b bao ng
Ni bao c ch to bng thp khng g, hoc bng ng. Hin nay, ch s dng ni bao bng thp
khng g, ni bao bng ng ch thch hp trong trng hp khng c h thng thi kh, khi nhit
c cung cp qua thnh ni. Ni c hnh cu hi dp, hnh qu l hoc hnh nhiu gc cnh. Ni c
lp nghing mt gc khong 30
o
, c gn vi mt ng c in quay vi tc 830 vng/pht. Ni
c h thng thi kh c th gia nhit cung cp kh nng khi cn thit sy vin. Kh thi c thot
ra ngoi t do hoc c ht ra bng h thng ht kh. H thng ht kh cng c s dng ht
bi t vin giai on u trc khi ti dch bao.
Ni bao kinh in c kh nng sy thp. Cc ni bao ci tin c th c h thng phun dch bao v h
thng thi kh nng c a thng vo gia khi vin, gip cho dch bao v khng kh nng tip xc
u vi khi vin.
11.2.5. Cc s c k thut trong sn xut vin bao ng
a) Cc s c lin quan cht lng vin nhn
Bao ng l mt quy trnh ko di thi gian v trong qu trnh bao cc vin phi chu nhng tc
ng c hc mnh, do , vin nhn phi cng, mi mn thp v khng b m v. Cc mnh v
hoc bi thuc thi ra t vin nhn c th bm ln b mt vin v lm cho c l vin nhn b hng.
b) Cc s c lin quan n dch bao v quy trnh bao
M lp bao
Lp bao ng thng rt dn v c th b m nu c nhng va chm mnh, trnh hin tng m
cnh c th lm cho lp bao bt dn bng cch cho thm polyme vo sir cc giai on bao. Cc
polyme c th dng gm gm arabic, gelatin, dn cht cellulose, PVP. Lp bao cha nhiu cht rn
khng tan (t dc n, cht mu) cng lm vin d b m cnh trong qu trnh bo qun.
Nt lp bao
Nguyn nhn chnh l do vin trng n trong tri gian bao v ngay sau khi hon tt m bao. S
trng n c th l do vin ht m hoc do vin trng n sau thi k gii nn (hin tng thng gp
vi vin ibuprofen).
Hin tng ny c th c khc phc bng cch bao cch ly vin vi cc polyme t thm m hoc

Hnh 11.1. Ni bao kinh in vi h thng
thi v ht kh.

Hnh 11.2. S nguyn tc hot ng
ca ni bao ci tin
khng thm m; vi cc vin c tnh chu nn thp, cn phi bo qun vin mt thi gian trc khi
bao vin.
Lp bao khng kh
Nu lp bao khng kh d sy tht k, nguyn nhn c th do c nhiu ng nghch chuyn
trong dung dch sir. Lng ng nghch chuyn c trong sir khng nn qu 5%. Nguyn nhn sinh
ra ng nghch chuyn c th l do sir c bo qun qu lu trc khi bao. Mt nguyn nhn khc l
do s nu li sir trong trng hp ng kt tinh. Sir c pha mu khng tan khng nn bo qun
qu lu, v cc mu khng tan thng c tnh acid, nn to iu kin cho phn ng thu phn xy ra
nhanh.
Vin dnh i
Nguyn nhn chnh l do hnh dng vin khng ph hp. Din tch tip xc gia cc vin phi rt
nh. Cc vin dng trong bao ng nn l vin c hai mt li.
Mu khng u
S phn b khng ng u ca cc cht mu c th do nhiu nguyn nhn khc nhau:
S phn b dch bao khng ng u trn vin: nguyn nhn chnh l do lng dch bao mu mi
ln thm khng lm t v bao ph ton b khi vin, hoc do khi vin khng c o trn u
nn dch bao mu khng phn b ng nht.
S loang mu khi bao bng dung dch mu tan.
Lp bao lt khng nhn dn n dy ca lp bao mu trn vin khng ng u hu qu l to
ra nhng m c cng mu khc nhau.
Lng dch bao mu mi ln ti qu nhiu, gy hin tng lp sau ho tan lp trc (cc lp bao
mu kh ti ho tan trong dch bao mu va mi thm), lp bao mu s c nhiu m hoc mu b
loang.
Sy qu kh sau mi ln thm dch bao mu s lm dch bao mu khng nhn to cm gic cng
mu khng ng u ti mi im trn vin.
S phn b khng ng u ca lp mu d pht hin khi s dng mu m. m bo ng
nht mu gia cc l, cn lu vin mu so mu v bao cho n khi mu ca vin ging nh mu ca
vin mu.
Ni ht (Blooming) hoc thm m (Sweating)
Nu vin khng c sy k trc khi bao, lng nc cn li trong vin c th khuch tn ra ngoi
lp bao. Nu hm m trong vin thp, lng nc thot ra c th lm m lp bao; nu hm m trong
vin cao, lng nc khuch tn c th kt t thnh ht trn b mt vin, cc vin ny c th dnh nhau
sau mt thi gian bo qun trong bao b kn. Hin tng thm m c th c khc phc bng cch sy
vin k trc khi nh bng.
Mt vin c vn (Marbling)
Mt vin bao thnh phm c vn c th do lp sp trn vin khng c phn b ng u, trnh
hin tng ny cn phi o vin v cung cp nhit y trong qu trnh nh bng. Mt nguyn nhn
khc gy ra hin tng c vn l do lp bao mu khng nhn nn lp bao bng khng ng nht
dy.
11.3. Sn xut vin bao phim
Bao phim l qu trnh ph mt lp mng mng ln cht rn. Lp bao trn cc sn phm bao phim
thng rt mng ch vo khong 10200 m. Cc cht rn c th l cc vin nn, vi ht, cm hoc cc
tinh th dc cht.
u im ca quy trnh bao phim:
So vi vin bao ng, lp bao phim thng rt mng khong 10100m, nn khi lng vin
ch tng khong 25%.
Thi gian bao nhanh hn.
Hiu qu v nng sut cao hn.
C th s dng cc cng thc bao v quy trnh bao ph hp ci thin sinh kh dng ca thuc.
Quy trnh c th t ng ho d dng.
L phng thc thch hp iu ch vin tan trong rut, vin tc dng ko di.
Quy trnh bao phim c th c thc hin bng phng php ti hoc phun, hin nay ch p dng
phng php phun dch bao.
11.3.1. C ch to thnh mng phim
Trong phng php phun, cc cht bao to thnh nhng git t rt nh, cc git cht bao thm t
b mt vin v kt t li thnh lp phim khi dung mi bay hi. Trong k thut bao phim cn iu chnh
cc thng s sao cho t c cn bng gia tc phun dch bao v quy trnh sy cc git cht bao
c th kh ngay sau khi thm t b mt vin.
Do s bay hi dung mi xy ra nhanh chng ngay khi cc git cht bao bm u vo vin, nn s
phn b cht bao va ph thuc vo s o trn ca ni va ph thuc vo cch phun dch bao ng
nht hay khng. Trong bao ng s phn b cht bao ch ph thuc ch yu vo s o trn dch
bao chuyn t vin t sang vin kh cho n khi c khi vin t u, nn khng cn thit tt c cc
vin nhn phi di chuyn qua vng ti dch bao. Trong bao phim, s sy kh phi vin kh ngay,
nu c s di chuyn dch bao cha kh t vin ny sang vin khc s gy nn hin tng vin b lc v
cam hoc r mt, nn cn thit tt c cc vin nhn phi di chuyn ngang qua vng phun dch bao.
Cc quy trnh bao phim thng c xem l quy trnh lin tc, do cht bao c phun lin tc t khi
bt u cho n khi kt thc. Tuy nhin, y l mt quy trnh gin on, bi v ch c mt phn ca khi
vin nhn di chuyn ngang qua vng phun dch bao, tip sau l giai on sy vin trc khi vin di
chuyn n vng phun.
Bao phim bng dung dch polyme l phng php c ng dng t rt lu. Cc polyme c
ho tan trong dung mi hu c nh aceton, isopropanol, cn, methyl chlorid.
Qu trnh hnh thnh lp phim t dung dch polyme ph thuc rt ln vo tc bay hi ca dung
mi. Hai yu t chnh nh hng n tc bay hi ca dung mi l nhit ho hi ca dung mi v iu
kin sy ca quy trnh bao. Qu trnh bay hi ca dung mi xy ra ngay t khi git cht lng ra khi u
phun dch bao, git cht lng s co th tch ngay trc khi tip xc vi vin v nht ca dung
dch polyme s tng ln. Khi tip xc vi vin, dung mi tip tc bay hi vi tc chm hn, c
kim sot bi s khuch tn ca dung mi qua mng polyme, cc phn t polyme sp xp li vi nhau
ti im ho rn. Sau khi hon tt m bao, dung mi vn tip tc bay hi vi tc chm trong mt
khong thi gian di. Tc bay hi trong giai on ny ph thuc vo cc khong trng gia cc phn
t polyme (c gi l th tch t do).
Trong qu trnh bay hi chm ny, th tch t do gim dn v nhit ho knh ca polyme tng
dn. Cui cng th tch t do gim n mc dung mi khng cn bay hi c na. loi c ton
b dung mi cn phi sy sn phm nhit cao hn nhit ho knh ca polyme, iu ny hon
ton khng th thc hin c v nhit ho knh ca cc cht bao kh cao, v d nhit ho knh
ca HPMC c th ln n 180 200
o
C.

Bao phim bng hn dch polyme l phng php bao dng h phn tn polyme trong nc. to
c mng phim, cc tiu phn polyme phi c kt t thnh mt lp lin tc. S sy c th loi c
dung mi d dng, nhng to c mng phim lin tc cn c thi gian di hn.
S to phim t hn dch polyme gm cc giai on:
Cc tiu phn cht rn tin n gn v tip xc vi nhau.
p sut mao qun c hnh thnh cc khe gia cc phn t polyme, khi p sut mao qun ln
hn lc y gia cc tiu phn polyme s lm cho cc tiu phn polyme bin dng
Cc tiu phn polyme lin kt vi nhau to thnh mng lin tc.
Qu trnh to mng ph thuc rt ln vo cc iu kin bao. S kt t ca cc tiu phn polyme c
trong hn dch ph thuc rt ln vo th tch t do. Nhit sy trong qu trnh bao phi cao hn nhit
ho knh ca polyme (hoc hn hp polyme cht ho do).
11.3.2. Thit b bao phim
Ni bao hoc thit b bao tng si
H thng cung cp v x l khng kh
Thng cha v khuy trn dch bao
H thng bm dch bao
H thng phun dch bao
a) Ni bao kinh in
Ni bao c dng bao phim t rt lu bng cch thm h thng phun dch v ci tin h
thng sy vin, tuy nhin khi ng dng trong bao phim, ni bao kinh in c ba nhc im chnh:
S sy kh ch c thc hin trn b mt khi vin; do cu to ca ni, lung kh nng khng th
i xuyn vo trong khi vin, nn hiu qu sy rt km. Do , trong bao phim, ni bao ng khng
th p dng bao vi dung mi nc.
Kh nng o trn rt km, c nhiu im cht (cc v tr vin khng c o trn u), nhc
im ny c khc phc bng cch o bng tay trong trng hp bao ng, nhng kh khc phc
trong bao phim.
S mt cn bng gia lung kh vo v kh thot do lung kh nng cung cp vo ni v kh thot
u lu thng qua t mt ca, va lm cho hiu qu sy km, ng thi lm dung mi thot ra khu vc
bao vin gy nhim.
b) H thng ni bao c l (Perforated pan system)
Ni bao c cu to gm ba phn, hai phn hnh cn hai bn, phn gia hnh tr c c l. Ni
c quay trn mt trc nm ngang vi tc khong 3 30 vng/pht.

Hnh 11.3. Thit k ca ni bao c l

Hnh 11.4. S di chuyn ca lung khng kh
sy vin trong ni bao c l
c) H thng bao tng si
H thng tng si c s dng sy v to ht trong
cng nghip dc phm. Sau ny c ci tin thnh h thng
bao bng cch thit k thm u phun dch bao. Tu theo v tr
u phun dch bao, cc h thng tng si gm ba loi: kiu
phun t trn xung, kiu phun t di ln v kiu phun tip
tuyn.
Kiu phun t trn xung: thit k cn bn ca h thng
ny tng t nh my to ht tng si nn h thng c th
c dng vi hai chc nng iu ch vi ht v bao vin hoc
vi ht.

Hnh 11.5. Nguyn l hot ng ca my
bao tng si kiu phun t trn xung
Kiu phun tip tuyn: Thit k c bit ca h thng ny
l khng c a phn phi kh, thay vo l mt a quay trn,
kh nn c cung cp cho bung bao qua mt khe hp gia a
quay v thnh thit b. Cc vin s chuyn ng trong bung
bao theo kiu xon thng, do s chuyn ng rt nhanh ny,
nn cc vin cn c bn c hc tt chu ng s va chm
mnh gia cc vin.
Kiu phun t di ln: cn c gi l h thng bao
Wurster. Trong h thng ny, cc l trn a phn phi kh c
a) H thng phun dch bao. C hai h thng phun dch bao c s dng: h thng phun khng
dng kh v h thng phun dng kh nn.
H thng phun khng dng kh nn cn c gi h thng phun cht lng p sut cao, hot ng
theo nguyn tc cho dng cht lng c nn p sut cao (3,5 20,0MPa hoc 500 3000PSI) i qua
mt l phun c ng knh rt nh (200 400nm), to thnh cc git cht bao. C nhiu kiu u
phun dch khc nhau c th iu chnh cc kiu phun khc nhau. Tc phun ph thuc vo p sut
cht lng, kch thc l phun v nht cht lng. Kch thc ht cht lng khi c phun ra ph thuc
ch yu kch thc l phun. Kch thc l phun dch rt nh, nn trong trng hp phun hn dch cc
tiu phn phn tn phi c nghin rt mn khng lm tc sng phun.
H thng phun khng dng kh c p dng nhiu quy m cng nghip v di phun n nh hn
khi phun tc cao v d kim sot cc thng s.
H thng phun dng kh nn c kh nng cung cp dch bao vi mt tc v mc n nh khi
cn phun tc thp n trung bnh. Hai b phn quan trng nht ca h thng l l cung cp dch bao
v l cung cp kh. L cung cp dch bao thng c kch thc kh ln (c th n 2 3mm), dch bao
c cung cp bng mt bm nhu ng, i qua l phun vi mt p sut tng i nh v c to thnh
tia mn nh mt lung kh nn vi p sut cao phun ra t l cung cp kh, do h thng ny c gi
l h thng kh ho p sut thp.

bao tng si kiu phun tip tuyn
kch thc khc nhau: ng knh ln trung tm v
ng knh nh hn vng ngoi.
Lung kh nn vng trung tm rt mnh y vin ln
cao v lung kh nn yu bn ngoi gip sy vin trong chu
trnh bao. Bn trong bung bao c thit k mt ct nh
(c gi l bung trong), kch thc tng ng vi vng c
l phn phi kh ln. Cc vin s i ln trong lng ct, ngang
qua vng phun dch v ri xung vng ngoi ct. u phun
dch bao c thit k gia a phn phi kh v phun t
di ln. Thit k ny bo m cho tt c cc vin u i qua
vng phun dch.
Cc h thng tng si c u im l kh nng sy rt cao,
rt thch hp cho mi loi dung mi khc nhau. Ngoi cng
dng dng bao, cc h thng ny cn dng to ht v
iu ch vi ht hoc iu ch vi nang.

bao tng si kiu phun t di ln
(kiu Wurster)
Kch thc v s phn b kch thc cc git cht lng c kim sot bng p sut v th tch kh
nn qua h thng. Mc phun ph thuc vo p sut cht lng, kch thc l phun dch v kiu l cp
kh.

Hnh 11.8. Sng phun dch bao kiu dng kh nn
H thng cung cp kh nn c th cho dy phun nhiu kiu khc nhau t hnh trn cho n oval
dy phun c th m rng v ph ln chiu ngang ca khi vin ang chuyn ng. Cn rt thn trng
khi iu chnh lung kh nn, nu lung kh nn qu mnh c th lm ri lon chuyn ng ca khi
vin hoc gy ra hin tng phun sy i vi git dch bao (dch bao kh trc khi chm vo vin
nhn). Trong trng hp cn c dy phun vt qu gii hn iu chnh ca h thng, cn phi s dng
nhiu sng phun t song song.
H thng phun khng dng kh thng c dy phun rng hn h thng dng kh nn; ph chiu
ngang mt khi vin ang chuyn ng trong ni bao vi kch thc 120cm c th dng hai sng phun
khng dng kh nn, nhng phi dng n 3 4 sng phun dng kh nn.
quy m sn xut ln, c hai loi sng phun u c th c s dng mt cch hiu qu, tu thuc
vo cng thc dch bao v tng sn phm c th.
H thng phun dch bao dng kh nn c s dng ph bin quy m nh v c th iu chnh
c tc phun v mc phun mt cch chnh xc, h thng ny cng rt thch hp khi bao vi dung
mi l nc.
11.3.3. Nguyn liu bao phim
Dch bao phim gm bn thnh phn chnh: polyme (cht to phim), cht ho do, cht mu v dung
mi. bao phim trong sut, c th khng s dng cht mu hoc cht to c. Trong mt s trng
hp cn thit c th s dng thm cc cht ph gia khc nh: mi thm, cht din hot, cht lm bng
v cht ph bt.

Hnh 11.9. u phun dch bao dng kh nn

Hnh 11.10. u phun dch bao khng dng kh nn
Nguyn liu bao phim l tng phi c cc tnh cht sau:
Tan c trong dung mi dng pha dch bao, trong trng hp khng tan c th cht bao phi
d dng phn tn thnh dng hn dch mn, c lng tht chm.
C tan ph hp vi mc ch bao vin: cc mng bao dng bao bo v phi tan nhanh trong
mi trng nc, cc mng bao tan trong rut phi c kh nng khng dch v, v kh nng ny phi n
nh trong thi gian bo qun.
Cc mng bao phim phng thch ko di phi gii phng thuc mt tc n nh.
C th to c mt mng phim mng, dai bn v p.
Khng mu, khng mi, khng v.
Bn vi tc ng ca nhit , m v khng kh. Mng phim khng b thay i trong qu trnh
bo qun nh thu phn chm hoc tip tc b polyme ho trong thi gian bo qun.
Khng tng k vi cc thnh phn khc c trong dch bao, khng tng k vi thnh phn ca
vin nhn.
Khng c, khng c tc dng dc l ring.
Thch hp cho cc phng php bao vin nn hoc vi ht.
Khng che lp cc logo.
Rt kh c th chn c cht bao p ng c tt c cc yu cu trn, nn trong tng trng hp
c th cn phi xc nh yu cu u tin.
Polyme: polyme l thnh phn chnh ca dch bao phim, v l cht c nh hng ln nht n cht
lng lp bao. c trng quan trng nht nh hng trc tip n cht lng mng phim l khi lng
phn t v nht.
Bng 11.1. nh hng ca nht v khi lng phn t n tnh cht mng phim
Cc polyme dng bao phim c chia thnh ba nhm chnh.
* Nhm polyme dng bao phim tan trong d dy:
Hydroxypropyl methyl cellulose (HPMC)
Hydroxypropyl cellulose (HPC)
Hydroxyethyl cellulose
Methylhydroxy ethyl cellulose
Carboxyl methyl cellulose
Na carboxyl methyl cellulose
Tnh cht nh hng khi tng khi lng phn t ca polyme
bn c hc Tng
Tnh kt dnh ca mng phim Gim
nht ca dch bao Tng
Tnh thm ca mng phim Thng khng nh hng, tr trng hp tnh cht c hc
ca polyme tng khi gia tng phn t lng polyme
Polyvinyl pyrrolidon (PVP)
Polyethylen glycol (PEG)
Dimethylaminoethyl methacrylatemethylacrylates acid ester copolyme
Ethylacrylatemethylmethacrylate copolyme (cc Eudragit)
* Nhm polyme dng bao phim tan trong rut
K thut bao phim tan trong rut c ng dng kh lu vi cc mc ch sau:
Trnh kch ng da dy hoc gy bun nn khi dc cht c phng thch ti d dy.
Bo v dc cht khi tc ng ca acid c trong dch v nh cc thuc c ngun gc enzym v
mt vi khng sinh.
Phng thch hot cht ti mt v tr nht nh trong rut duy tr nng thuc cao, v d cc
thuc dng st khun ng rut nn c r ti rut hn ch s gim hm lng ca thuc, do thuc
b hp thu ti d dy.
i vi thuc c vng hp thu ti u ti rut, cc vin nn bao tan trong rut s phng thch thuc
ti rut non v s tp trung nng thuc ti rut non s cao nn sinh kh dng ca thuc s cao hn.
Cho n nay c khong 60 cht dng bao phim phng thch dc cht ti rut non:
Nhm th nht gm cc cht bao phng thch dc cht do mn dn trong h tiu ho nh sp
carnauba, acid stearic, du thu du hydrogen ho, ceresin, specmaceti, gelatinformaldehyd, keratin,
gluten, casein, zein Nhm cht ny i hi dng thuc phi xung n rut non trc khi b bo mn
hon ton. S phng thch dc cht ca cc dng thuc c bao bi nhm cht ny ph thuc rt
nhiu vo thi gian lu ca dng thuc trong d dy nn hin nay t c dng.
Nhm cht to phim th hai l cc polyme khng tan trong mi trung dch v, nhng tan tt mi
trng c pH t 4,5 tr ln. Cc cht to mng phim tan trong rut l cc polyme mch di c cha cc
nhm carboxyl. pH thp ca dch v, cc nhm carboxyl ny khng ion ho nn khng tan trong mi
trng nc, pH cao ca mi trng dch rut, cc nhm ny b ion ho v tan trong nc d dng.
Cc polyme trong nhm ny gm:
Cellulose acetate phtalate (CAP): c phn t lng khong 20008000, khng tan trong nc, cn,
hydrocarbon, tan d trong hn hp cnether, ceton. CAP c th c dng di dng dung dch trong
dung mi hu c hoc hn dch trong nc. Vin nn bao bng CAP r pH khong 6,5.
Hydroxypropyl methyl cellulose phtalate (HPMCP): Trn th trng c ba dng l HP50, HP55 v
HP55S. Vin nn bao bng HP50 r pH 5,0; bao bng HP55 v HP55S r pH 5,5; dung dch
HP55S c nht cao hn dung dch HP55 c nng tng ng.
Cc HPMCP tan c trong cc dung mi hu c, dung mi ho tan tt nht l methylchlorid hoc
hn hp cnnc.
Polyvinyl acetat phtalate (PVAP). Vin bao bng PVAP r c pH 5. PVAP tan c trong
methanol, ethanol, hn hp acetonmethanol.
Cellulose acetate trimelitate (CAT), vin c bao bng CAT r c pH 4,5.
Hydroxypropyl methyl cellulose acetate succinate (HPMCAS).
Eudragit S100 cho vin r pH t 7 tr ln.
Eudragit L100 cho vin r pH t 6 tr ln.
Eudragit L 10055 cho vin r pH t 5,5 tr ln.
Cc polyme c tan theo pH thng c bn cht ester, nn c th b thu phn, mc thu phn
tu theo tng loi polyme, cellulose acetat phtalat l cht d b thu phn nht. Nhit v hm m cao
trong thi gian bo qun l tc nhn thc y phn ng thu phn. Khi cc polyme ny b thu phn, sn
phm s khng cn tnh khng dch v. Do , th nghim ho tan (hoc r) nht thit phi c thc
hin trong chng trnh th n nh.
Khi chn cht bao tan trong rut cn lu n mt s yu t nh hng n kh nng khng dch v
ca mng phim:
Bn cht ca dc cht.
T l polyme so vi khi lng vin: khng c mt t l nht nh cho tng loi vin v mi loi
cht bao, nn cn phi xc nh bng thc nghim. Nu khng t c t l ti u vin c th r trong
mi trng pH thp, hoc ngc li kh r trong mi trng pH cao.
pH m ti polyme tan.
Thi gian lu ca dng thuc trong ng tiu ho, thi gian ny thng chm i vi dng vin
bao tan trong rut, trong trng hp cn thit c th iu ch di dng vi ht bao tan trong rut dp
vin hoc ng nang.
*Nhm cht bao phng thch ko di.
Cc polyme dng iu ch vin nn phng thch ko di thng to mng phim phng thch dc
cht theo kiu khuch tn, khi cha tip xc vi dch tiu ho hoc mi trng, lp bao l mt mng lin
tc, khi tip xc vi mi trng, mng phim trng n to thnh nhng knh khuch tn phng
thch dc cht.
Cng c th iu ch vin phng thch ko di h mng bao ho tan bng cch bao cc ht bng cc
cht bao c tan khc nhau c sn phm phng thch theo nhiu thi im.
Mt s dn cht ca nhm cellulose c th c dng to mng phim phng thch ko di nh
ethyl cellulose, cellulose acetat, cellulose triacetat, cc cht ny khng tan nhng trng n trong nc
vi cc mc khc nhau. Tnh thm ca mng phim c th c iu chnh bng cch phi hp vi
cc polyme tan trong nc nh HPMC, PEG, PVP hoc phi hp vi cc cht to knh khuch tn
dng ht rn khng tan trong nc.
Cc dn cht methacrylat c cha nhm amoni bc 4 nh Eudragit RS100 v Eudragit RL100 c th
dng to mng bao thm thu m khng cn cc cht ph gia, tnh thm nc ca cc polyme ny
ph thuc trc tip vo t l nhm thn nc trong phn t polyme: Tnh thm nc c th c iu
chnh bng cch phi hp hai polyme ny nhiu t l khc nhau.
Tc phng thch dc cht c th c iu chnh bng cch phi hp vi cc polyme khng
cng nhm nh cc polyme tan trong mi trng acid hoc polyme tan theo pH. V d phi hp HPMC
vi EC; Eudragit RS100 vi Eudragit S100, Eudragit RL100 vi Eudragit L100 hoc Eudragit RS100
vi Eudragit NE 30D.
Mt phng php khc l bao vin bng mt mng bn thm, sau dng tia laser to mt l
thuc phng thch ra ngoi. Tc phng thch dc cht trong h ny ph thuc vo kch thc l
phn phi thuc, dy mng bao v p sut trong nhn.
Mt cch khc iu chnh tc phng thch dc cht l cho thm cc cht to p sut thm
thu trong nhn.
Hnh 11.11. Vin phng thch dc cht ko di bng p sut thm thu
(a) nh chp b mt; (b) nh chp mt ct
Cht ho do
Khi nim v trng thi knh v nhit ho knh. Hu ht cc polyme dng bao phim l cc cht v
nh hnh, khi nhit polyme b h thp n mt nhit ti hn gi l nhit ho knh (Glass
transition temperature Tg) th polyme s c mt s thay i ng k v tnh cht, do s chuyn ng
tng i ca cc phn t polyme b ngng li. Khi polyme cn c cung cp nng lng tr v
trng thi bnh thng, nu nng lng nhit cung cp khng , nhit ca polyme thp hn Tg,
polyme s th hin tnh cht ca knh: cng v dn.
Do nhit ho knh ca hu ht cc polyme u cao hn nhit sy p dng trong cc quy trnh
bao, nn cn thit phi thay i nhit ho knh ca cc polyme. S dng cht ho do l phng php
hu hiu nht iu chnh tnh cht c nhit ca polyme. Cc cht ho do l cc cht c phn t
lng thp so vi polyme, cht ny lm gim nhit ho knh (Tg) v lm polyme t th rn thnh
polyme dng mm do hn. Yu cu cn bn ca cht ho do l phi tng thch vi polyme. S tng
thch vi polyme th hin kh nng trn ln c vi polyme v phi to c nhng lin kt lin
phn t vi polyme. Kh nng tng hp vi polyme c xc nh bng cc phng php nhit ng
hc.
Mi loi cht ho do u c nhng tnh cht ho l ring, nn vic la chn cht ho do phi cn
c vo loi polyme c dng. Khng c cht ho do no c th dng cho tt c cc loi polyme. Do
, nu dng nhiu loi polyme phi hp vi nhau, c th phi dng nhiu loi cht ho do tng ng.
Trong trng hp to mng bao bng h phn tn polyme trong nc, cht ho do ng mt vai tr
quan trng trong vic to ra v duy tr th tch t do nhit bao nhm gip cho s to thnh mng
polyme lin tc.
Ngoi tnh cht lm cho mng phim bt dn, cht ho do cn c th ci thin c nhiu tnh cht
khc nhau ca mng phim, nn cht ho do c vai tr quan trng trong iu ch mng phim phng

(a)

(b)
thch ko di.
Bng 11.2. nh hng ca cht ho do n tnh cht ca mng phim
t c cc mc tiu ny, cht ho do phi c phn b vo gia chui polyme tng tc
vi cc nhm chc ca polyme nn lm gim tng tc gia cc nhm chc polyme vi nhau, c ch
ny lm cho mng phim mm do hn.
Cc cht ho do thng dng:
Nhm cn a chc: Propylen glycol, glycerol, polyethylen glycol.
Nhm ester acetate: Glycerin triacetat (Triacetin), Triethyl citrat (TEC), acetyl triethyl citrat.
Ester phtalate: Diethyl phtalate (DEP).
Glycerid: monoglycerid acetyl ho.
Du: du thu du, du khong.
Dung mi
Dung mi c dng ho tan v phn tn cc polyme, ng thi gip polyme phn b u trn b
mt vin.
Nc. Vi dn cht cellulose nh HPMC hoc ethyl cellulose c th ho tan thnh dung dch trong
nc, do c th ho tan iu ch thnh dung dch bao trong nc. Dung dch polyme trong nc
c nht kh cao nn ch c cc loi polyme c phn t lng thp nh Methocel E3, E5 hoc
Pharmacoat 603, 606 c dng bao di dng dung dch c nng trong khong 510% trong
nc.
Cc cht khng tan trong nc c dng bao di dng hn dch trong nc. Khi bao dng hn
dch, cc tiu phn polyme phi c kch thc rt nh khng lm tc sng phun v cho lp phim lng,
mn.
Dung mi hu c. u im ca cc loi dung mi hu c l c nhit ho hi thp, bay hi nhanh
nn c th bao trong iu kin sy km v rt ngn thi gian bao.
Cc dung mi thng dng trong bao phim gm ethanol, methanol, isopropanol, aceton,
dichloromethan, trichloromethan.
Bng 11.3. Nhit si v nhit ho hi ca mt s dung mi thng dng
Tnh cht nh hng khi tng nng cht ho do
dnh ca mng phim C th tng
nht ca dch bao Tng, mc tng thay i theo tng loi cht ho do
Tnh thm ca mng phim C th tng hoc gim tu thuc vo tng loi polyme
Nhit ho knh Gim, mc gim tu thuc vo kh nng tng thch vi polyme.
Dung mi
Nhit si (
o
C)

Nhit ho hi (J/g)
Ethanol 78,3 855
Hn hp dung mi thng c s dng vi mc ch gim nht ca dch bao, gim nhit ho
hi ca hn hp. nht ca dch bao nn vo khong 150500 Cps (i vi h thng phun dng kh
nn) nht thp gip dung mi thm t b mt vin tt hn to thnh mng phim lin tc.
Hn hp dung mi thng dng gm ethanolnc i vi cc dn cht cellulose hoc aceton
isopropanol i vi dn cht ca acid methacrylic.
Cht mu
Hu nh cc cht mu khng c tc dng trc tip n hiu qu tr liu ca thuc, cht mu ch gip
phn bit gia cc vin trong qu trnh sn xut v lu hnh.
Cc cht mu dng trong bao ng v bao phim vin nn phi l cc cht mu t tiu chun dng
trong dc phm.
Theo quy nh ca Hoa K, cht mu c th thuc vo cc tiu chun sau:
Tiu chun FD&C: l cc cht mu c dng trong thc phm, dc phm v m phm.
Tiu chun D&C: cc cht mu c dng trong dc phm v m phm.
External D&C: cc cht mu ch c dng trong cc m phm v dc phm dng ngoi.
Cc cht mu t tiu chun ca Cng ng chung chu u thng c k hiu l E, v d: E 121 l
m mu ca carmin.
Tu thuc vo tan, cc cht mu dng trong dc phm c chia thnh hai loi l mu tan (dye)
v mu khng tan (lake).
Mu tan trong nc: thng c ngun gc tng hp, ch yu l tng hp t cc sn phm ph trong
cng nghip du kh. Cc cht mu c th c cung cp di dng bt, dng ht, dng dung dch hoc
dng hn dch. Cc loi mu tan thng khng bn, c th b phai bi cc yu t nh nh sng, cht oxy
ho, cht kh, vt kim loi nng, pH, nhit cao v vi sinh vt.
Bng 11.4. Mt s cht mu theo tiu chun FD&C v D&C
thng dng trong bao phim vin nn
Methanol
Isopropanol
Aceton
Dichloromethan
Trichloromethan
Nc
64,7
82,3
56,2
40,1
61,2
100,0
1102
667
520
321
247
2264
Tn cht mu K hiu
Brilliant blue FD&C blue # 1
Indigotin FD&C blue # 2
Erythrosine FD&C red # 3

Bng 11.5. Mt s cht mu theo tiu chun chu u
thng dng trong bao phim vin nn
Mu khng tan trong nc: c ch to bng cch cho cc cht mu kt ta ln cc cht nn nh
mui nhm. So vi mu tan trong nc, cc mu khng tan thng bn hn khi b tc ng bi cc yu
t nh nh sng, cht oxy ho, nhit Mu khng tan theo tiu chun FD&C c ch to t mu
tan t tiu chun FD&C vi cht nn duy nht c chp nhn l mui nhm. Mu khng tan theo tiu
chun D&C v external D&C c ch to bng cch kt ta cc cht mu t tiu chun D&C vi cc
cht nn khc nhau nh mui nhm, titan dioxyd, km oxyd, talc, nhm oxyd, calci carbonat.
La chn cht mu: Cc mu tan t c dng trong trng hp bao bng dung mi hu c do hn
ch ca tan. Trong trng hp bao bng dung mi nc c th s dng cc mu tan, tuy nhin cn
lu n hin tng loang mu v bn mu ca mi loi cht mu khc nhau. C th s dng cc
cht mu khng tan phn tn trong h dch bao. Trong trng hp ny, cc cht mu phi c kch thc
ht tht mn v c phn tn ng nht lp mu phn phi u trn vin v khng lm tc sng
phun.
11.3.4. Cc thng s cng ngh trong k thut bao phim
Cht lng vin nhn, cng thc dch bao v quy trnh bao l cc yu t cn bn quyt nh cht
lng vin bao.
So vi bao ng, k thut bao phim n gin hn v khng phi tri qua nhiu giai on bao vi
cc thnh phn dch bao khc nhau. Tuy nhin, quy trnh bao phim i hi phi kim tra rt nhiu bin
s c th t c hiu qu bao ti u nht.
a) Cc bin s ca ni bao
Ponceaux FD &C red # 4
Tartrazine FD &C yellow 5
Sunset yellow FD&C yellow # 6
Tn cht mu K hiu
Allura red AC E132
Brillian blue FCF E133
Carmin E120
Erythrosine E127
Oxyd v hydroxyd st E172
Patent blue E131
Ponceau 4R E124
Riboflavin E101
Titan dioxyd E171
Indigotin E132
Quynollin yellow E104
Ni bao c chc nng o trn u khi vin trong qu trnh bao. S di chuyn v trn u ca khi
vin trong ni ph thuc vo nhiu yu t: kiu dng ni, s lng v cch thit k cnh o, tc
quay ca ni v ti trng ca ni.
Tc quay ca ni va nh hng n s trn u ca khi vin va nh hng n tc di
chuyn ca cc vin qua vng phun dch. Tc ni qu chm s gy t cc b, cc vin s dnh vo
nhau (nh hng n cht lng vin bao) hoc dnh vo thnh ni (gim hiu sut bao). Tc ni
quay qu nhanh, thi gian sy vin s ngn: cc vin khng kp kh trc khi tr li vng phun dch, kt
qu b mt lp bao khng nhn. Tc quay ca ni thng c iu chnh trong khong 10 15
vng/pht i vi trng hp bao bng dch bao pha trong dung mi hu c trn ni bao c ln; trong
trng hp bao bng dch bao pha trong nc, tc ni phi chm hn trong khong 3 8 vng/pht,
ng thi phi gim tc phun dch bao vin kp kh trc khi n vng phun dch. Tc quay
ca ni phi ph hp vi iu kin thit b, tnh cht dch bao v loi vin.
Kiu dng vin nh hng rt nhiu n s trn u ca khi vin trong ni bao. Cc vin hnh tr
dt hai mt li di chuyn u n trong ni bao v c th tip xc vi vng phun dch bao nhiu v tr
khc nhau; cc vin hnh thun di (vin hnh bu dc hoc caplet) thng kh bao v vin c khuynh
hng trt theo chiu dc ca vin.
Cc cnh o gip khi vin c trn u hn, tuy nhin cnh o s to ra mt tc ng c hc
lm cho vin b m cnh hoc nt nu vin c bn c hc thp, hoc c hnh dng khng thch hp.
b) Cc bin s phun dch bao
C ba bin s lin quan n s phun dch cn c kim sot cht ch l tc phun dch bao, kiu
phun dch bao v mc phun dch bao (kch thc v phn b kch thc ca git cht lng khi ra
khi sng phun).
Trong h thng phun dch khng dng kh nn, c ba bin s ny b chi phi bi p sut dch bao v
kch thc l phun dch bao.
Trong h thng phun dng kh nn, tc phun dch bao ph thuc p sut cht lng (c iu
chnh bng h thng bm nhu ng hoc bm piston) v kch thc l phun; mc phun ph thuc
vo p sut kh, th tch kh v thit k ca l phn phi kh u sng phun.
Tc phun dch bao phi ph hp vi s o trn, kh nng sy ca thit b, cng thc dch bao v
tnh cht ca vin nhn.
Kiu phun dch bao phi c iu chnh sao cho c c dy phun ph ht chiu ngang ca khi
vin ang chuyn ng. Nu dy phun qu rng, hiu sut bao s km do dch bao bm trn thnh ni;
nu dy phun hp s lm t cc b v s phn phi dch bao trn vin khng ng nht. c dy
phun ph hp, c th iu chnh khong cch gia u phun dch v b mt khi vin hoc iu chnh
p sut kh hoc hng phun dch bao.
Bin s kh iu chnh nht l mc phun dch bao (th hin kch thc v phn b kch thc
git dch bao) do bin s ny ph thuc rt nhiu yu t nh thnh phn dch bao, kch thc l phun
dch, p sut dch bao, p sut kh nn, th tch kh nn, nht dch bao Trn thc t, s iu chnh
mc phun ch da vo kinh nghim. t c mc phun thch hp c th iu chnh p sut
dch bao (i vi h thng phun khng dng kh nn) hoc iu chnh p sut kh nn (i vi h thng
phun dng kh nn). Nguyn tc chung l p sut dch bao hoc p sut kh nn cng cao th git cht
bao cng mn.
Git dch bao c kch thc qu nh c th s b kh trc khi tip xc vi vin do hin tng phun
sy, kt qu l hao ht dch bao v sn phm c b mt khng lng. Hin tng ny c th c pht
hin trong qu trnh bao v c nhiu bi bm trn thnh ni bao. Git dch bao c kch thc to s lm
dnh vin hoc gy lc v cam.
c) Bin s kh ca qu trnh sy vin
t c hiu qu sy ti u nht cn phi kim sot th tch, tc , hm m v nhit ca
khng kh dng sy vin.
Nhit kh cn la chn sao cho ph hp vi n nh ca dc cht v n nh ca mng
phim. Kh nng sy ca lung kh nng cn ph thuc vo hm m ca lung kh. Hm m cng cao,
kh nng sy cng thp v ngc li. t c mt hiu qu sy n nh cn kim sot cht ch hm
m ca mi trng hoc kh m lung kh trc khi qua b phn t nng.
11.3.5. Cc s c k thut trong bao phim vin nn
Tng t trong k thut bao ng, bao phim l mt qu trnh lm cho vin nhn chu nhiu tc
ng c hc. Cc tc ng c hc c th lm cho nhiu vin hoc ton b l sn phm b h hng trong
qu trnh bao. Cht lng vin bao ph thuc vo ba yu t cn bn: cht lng vin nhn, thnh phn
dch bao (lin quan n cht lng mng phim) v cc thng s ca quy trnh bao.
Khuynh hng chuyn t bao phim bng dung mi hu c sang bao phim bng dung mi nc lm
cho k thut bao tr nn phc tp hn, i hi quy trnh bao phi c kim sot cht ch gim thiu
cc s c k thut nh hng n cht lng sn phm.
Cc s c thng gp trong k thut bao phim gm:
a) Dnh vin
S dnh vin thng xy ra khi cc vin tip xc vi nhau trong lc dch bao cha kp kh. Cc vin
dnh nhau thng tch ri nhau ra sau mt vi vng quay ca ni (do s va chm nhau ca cc vin) lm
cho cc lp bao c th bong trc. Nguyn nhn gy ra hin tng ny l do tc phun dch bao cao
lm cho ton b khi vin b t; hoc mt phn khi vin b t do s lng sng phun khng
ph ton b b mt khi vin, hoc c s lng sng phun nhng mt sng phun b tc trong qu
trnh bao nn dch bao c phun ra nhiu cc sng cn li. S c dnh vin cng c th gy ra do kh
nng sy (nhit , lu lng kh) cha .
Cc cht to phim c tnh dnh cao cng c th gy nn
hin tng dnh vin.
Cch khc phc:
Gim tc phun dch bao.
Tng kh nng sy.
Tng tc ni bao.
Tng th tch/ p sut kh nn.


a) b)
Hnh 11.15. a) Bc cu logo; b) Mng bao bm dnh tt vo logo
Nguyn nhn ca hin tng bc cu logo c th do: (1) logo trn nhn qu mnh hoc qu chi tit
(2) dch bao c dnh qu cao v (3) tc phun dch bao qu cao.
Tng s lng sng phun.
b) Mt vin khng lng (si v cam)
Trong k thut bao phim, cn phi iu chnh cc thng
s cc git cht bao kh trong mt thi gian ngn sau
khi tip xc vi b mt vin, trn thc t iu ny rt kh.
Lp bao phim thng khng tht nhn nh lp bao ng.
Tuy nhin lp bao phim khng c
th nhm n mc c th pht hin c bng cm quan.
Nguyn nhn gy nn hin tng mt vin th nhm l
do (1) nht ca dch bao qu cao, sc cng b mt ca
dch bao cao nn khng tri u trn vin c, (2) tc
phun dch bao qu thp nhng tc sy qu nhanh, (3)
git cht bao qu mn nn kh trc khi bm vo vin.
c) Bc cu logo
Bc cu logo l hin tng mng phim khng bm vo
vin nhng ch chm khc, to nn nhng khng kh
gia mng bao v vin nhn, ng thi lm cho logo b mt
nt.
Hnh 11.12. Lp bao b trc
do vin b dnh nhau

Hnh 11.13. Mt vin b si v cam

Hnh 11.14. Vin b hin tng bc cu logo
d) Lp y logo
Logo c th b mt nt do cc cht c trong thnh phn dch bao
lp logo y hoc vin nhn b mn ti v tr logo; khng kh trong
dch bao v cht bao kh sm cng l mt nguyn nhn gy nn hin
tng lp y logo.
S c lp y logo c th c khc phc bng cch:
Tng bn c hc ca vin nhn (tng lc nn hoc thay i
cng thc vin nhn).

Gim p sut kh nn hoc gim nhit sy hoc tng tc phun dch, trnh trng hp cc
git dch bao kh trc khi tip xc b mt vin.
e) Trc lp bao (lc v cam = orange peeling) l hin tng lp bao b bong, trc tng mng ln.
Hin tng ny thng gp khi bn c hc ca lp bao km hoc lp bao khng dnh vo nhn.
S c c khc phc bng cch chn cht bao c bn c hc cao hn v/hoc c dnh tt
hn.
Loi kh trong dch bao trc khi phun dch.
Hnh 11.16. Logo b lp
g) Vin dnh i
Vin dng cho bao phim nn c b mt tip xc gia cc
vin tht nh, nn vin c dng cng gn hnh cu cng tt. Tc
phun dch qu cao gy t cc b hoc ton khi vin u c
th lm cho vin b dnh i. Vin cng c th b dnh nhau nu
tc ni bao qu chm.
h) Vin nhn b mn
Vin nhn c th b bo mn nhanh trong giai on u ca
quy trnh bao do s chuyn ng mnh trong ni bao. S bo
mn vin nhn c th lm cho mt vin x x do cc bi thi ra
t vin ny bm vo b mt ca vin khc.
Trong trng hp ny nn thit k cng thc li vin
nhn c bn c hc cao hn: Nu khng th tng bn c
hc ca vin bng cch thay i t dc c th thay i quy
trnh dp vin, v d chuyn t phng php dp thng thnh
phng php xt ht.
S bo mn cng c th trnh c bng cch gim tc
quay ca ni, tng tc phun dch bao v cn lm nng vin
hoc gim tc phun giai on u.
Mu khng u gia cc vin
Nguyn nhn chnh l s o trn ca ni cha tt hoc dy
phun khng ph ht chiu ngang ca khi vin ang chuyn
ng, lp bao qu mng, khng to mu hoc che lp mu
bn trong, hm lng cht rn qu cao.
Khc phc:
Bao dy hn hoc to mu vin nhn bng t dc mu
cng loi nhng nht hn
Tng tc ni hoc tng kh nng khuy trn ca thanh
o.
Bao lt trc khi bao mu. Ci thin t dc mu trong

Hnh 11.17. Vin dnh i do
thnh vin qu dy

Hnh 11.18. Vin nhn b xi mn

Hnh 11.19. Mu phn b khng

TI LIU THAM KHO
1. Stuart C.Porter and Charles H.Bruno. Coating of Pharmaceutical Solid Dosage Forms, in
dch bao.
i) Vin dnh thnh khi
Vin dnh thnh khi l hin tng thng xy ra do vin
cha c sy kh hon ton sau quy trnh bao, hoc vin
c sy kh hon ton nhng cht bao c tnh dnh qu cao,
hm lng cht ho do ln.
Trong trng hp ny cn sy k vin sau khi ngng phun
dch bao, hoc thay i t l hoc loi cht ho do trong dch
bao.
Sau khi bao xong, nn vin trong ni bao n khi vin
ngui n nhit phng, thnh thong cho ni quay o
trn, trc khi cho vo bao b.
k) Vin b mn hoc m cnh
Nguyn nhn gy mn, m cnh c th l do vin nhn c
mi mn qu cao, chy dng dp vin qu mn hoc cnh vin
qu mnh khng chu ng c cc tc ng c hc trong qu
trnh bao.
Nguyn nhn mn, m cnh cng c th do lp bao c
bn thp hoc hm lng cht rn thp.
Ngoi ra cn c th do cc thng s ca quy trnh bao gy
nn nh tc quay ni qu nhanh.
l) Nt vin
Nguyn nhn ch yu gy nt vin l do bn c hc ca
mng phim qu thp, mng phim qu dn hoc do s dn n ca
vin khng ng nht, c bit l i vi trng hp cc vin
cha dc cht c tnh chu nn thp gy nn hin tng trng
n chm thi k gii nn.
Khc phc :
iu ch li dch bao, thm hoc thay cht ho do.
Trnh dng cc t dc n thuc nhm v c (Ca
carbonat, Ca sufat, Mg carbonat) khi iu ch vin nhn.
vin n nh mt thi gian sau khi dp.
ng u gia cc vin

Hnh 11.20. Vin dnh thnh khi

Hnh 11.21. Vin b m cnh

Hnh 11.22. Vin nhn b nt
Pharmaceutical Dosage Forms; Tablets, vol 3, Marcel Dekker, 1990.
2. Edward J.Woznicki and David R.Schoneker. Coloring Agents for Use in Pharmaceutical, in
Encyclopedia of Phamaceuticals, Vol 3, Marcel Dekker 1990.
3. Klaus Lehmann, Brianca Brogmann, Tablet Coating, in Encyclopedia of Phamaceuticals, Vol 14,
Marcel Dekker 1996.
4. Remingtons Pharmaceutical Science, 1995. Chapter 93, Coating of pharmaceutical dosage
forms.

CU HI LNG GI * CHN CU TR LI NG NHT
1. Loi ng no c th bao bng phng php phun:
a) Saccharose; b) Xylitol;
c) Mannitol; d) Glucose;
e) Maltitol.
2. Nng ng saccharose thch hp dng trong k thut bao ng:
a) 2030%; b) 3040%;
c) 4050%; d) 5060%.
e) trn 65%;
3. Tnh cht no khng thuc v u im ca ng saccharose trong k thut bao ng?
a) Tan d dng trong nc; b) Kt tinh nhanh
c) Dung dch c nht cao; d) Khng ln ng n
4. H s kt tinh ca ng saccharose:
a) 1,03; b) 1,13;
c) 1,23; d) 1,33;
e) 1,43.
5. Yu cu v tnh kt tinh ca ng:
a) Kt tinh ngay khi va c vo khi vin;
b) Kt tinh thnh tinh th rt mn;
c) Kt tinh dng tinh th hnh kim;
d) Ch bt u kt tinh sau khi phn phi u trn khi vin.
6. S hin din ca ng glucose gy nn hin tng:
a) Mt vin r;
b) Vin dnh i hoc dnh thnh khi;
c) Lp bao khng kh;
d) Mu trn mt vin bao thnh phm khng sng;
e) Mu khng u.
7. Nguyn nhn c ng nghch chuyn trong sir ng:
a) C sn trong nguyn liu;
b) C sn trong cht mu;
c) Do nu sir nhit qu cao;
d) Sinh ra trong qu trnh bao, nht l giai on sy vin.
8. Nguyn liu no cho lp bao chng m tt, nhng tan rt nhanh?
a) Saccharose; b) Xylitol;
c) Mannitol; d) Glucose;
e) Maltitol.
9. Cch khc phc dn ca lp bao xylitol:
a) Thm gelatin vo dch bao;
b) Bao nhit thp;
c) Thm gm Arabic vo dch bao;
d) Cho ni quay chm trong qu trnh bao;
e) dch bao n nh qua m trc khi bao.
10. Cc cht bao thng dng trong giai on bao bo v ca quy trnh bao ng:
a) Cc loi cht rn v c; b) Shellac;
c) PEG; d) Ethyl cellulose;
e) Gelatin.
11. Nguyn liu chnh dng trong bao lt ca quy trnh bao ng:
a) Sir ung vi nng cao;
b) Cc cht v c dng rn;
c) Cc loi tinh bt;
d) ng lactose;
e) Cc dn cht cellulose.
12. Phng php no nn p dng rt ngn thi gian bao lt?
a) Phun bng sng phun khng dng kh nn;
b) Bi bng dch bao bt lun phin;
c) Bao bng hn dch;
d) Thm cc polyme vo dch bao.
13. Hin nay k thut bao phim c p dng nhiu l do:
a) Vin bao phim bng lng, nhiu mu sc p;
b) Thi gian thc hin bao phim nhanh hn bao ng;
c) Mng phim c tnh khng m v cc iu kin bt li ca mi trng tt hn bao ng;
d) Trang thit b n gin.
14. u im ca h thng phun dch bao khng dng kh nn.
a) C th iu chnh di phun d dng;
b) Di phun khng b nh hng bi nht ca dch bao;
c) Di phun n nh khi phun tc cao;
d) Git dch bao rt mn.
15. u im ca h thng phun dch bao dng kh nn:
a) Di phun hp;
b) t tiu tn dch bao;
c) C th iu chnh mc v tc phun dch bao chnh xc;
d) Phun c dch dng hn dch.
16. Nhc im ca h thng phun dch bao dng kh nn:
a) Khng phun c dch bao c nht ln;
b) Khng dng bao cc dung mi d gy chy n;
c) Di phun hp nn phi dng nhiu sng phun trong ni bao ln;
d) t tin.
17. Lng dch bao phim cn thit cho mt m bao ph thuc vo:
a) Tng din tch b mt ca vin nhn;
b) dy ca lp bao;
c) Hnh dng ca vin nhn;
d) C a v b.
18. Yu t no t nh hng n cht lng vin bao phim nht?
a) Cht lng vin nhn;
b) Mc hin i ca thit b;
c) Quy trnh bao;
d) Cng thc dch bao.
19. Nguyn nhn chnh lm mu gia cc vin khng u l do:
a) Tc phun dch qu cao;
b) Ch sy khng thch hp;
c) Lng dch bao qu t, lp bao qu mng;
d) Tc ni bao khng ph hp.
20. Nguyn nhn chnh lm nt vin trong k thut bao phim:
a) Mng phim qu mng;
b) Vin trng n;
c) Dung mi bay hi qu nhanh;
d) Tc phun dch bao qu nhanh.

Bi 12
CNG NGH BO CH VIN NANG CNG

12.1. Khi qut v thuc vin nang
12.1.1. nh ngha
Thuc nang l dng thuc ung cha mt hay nhiu hot cht trong v nang cng hay mm vi
nhiu kiu dng v kch thc khc nhau. V nang c lm t gelatin v c th c thm cc cht
ph gia khng gy c hi cho c th ngi. Thuc nang cng c v nang gm hai phn hnh tr lng
kht vo nhau, mi phn c mt u kn, u kia h. Thuc ng trong nang thng dng rn (bt hay
cm). (Dc in Vit Nam III).
Trn thc t, dc cht bn trong c th dng rn nh bt thuc, cm, vi ht, vi nang v cng c
th dng lng.

Hnh 12.1. Cc dng dc cht c th ng vo nang cng
1. Bt hoc cm thuc; 2. Vi ht hoc vi nang; 3. Vin nn; 4. Hn hp bt thuc + vi nang;
5. Bt (cm) thuc + vin nn; 6. Vi nang + vin nn; 7. Hai loi vi ht hoc vi nang;
8. Vin nang + vi ht; 9. Cm thuc + vin nang; 10. Thuc dng lng.
12.1.2. u im ca vin nang cng
Vin nang l dng vin d ung, d nut v c mu sc phong ph hn dng vin nn.
Dc cht ng vo vin nang c th nhiu dng: bt, cm, vi ht, vi nang, vin nang nh, vin
MC TIU
Trnh by c cc dng thuc vin nang.
Nu c cc tnh cht ca v nang v cch bo qun thch hp.
Phn tch c nguyn l hot ng ca cc my ng nang bn t ng v t ng.
Thit lp c cng thc c bn cho vin nang cha thuc dng bt v cm.
Trnh by c s quy trnh sn xut vin nang cng.
nn hoc phi hp cc dng trn trong cng mt v nang.
S phi hp ny c th gip cch ly cc thnh phn tng k hoc iu ch vin nang phng thch
ko di bng cch phi hp cc vi ht hoc vi nang phng thch dc cht ti nhiu thi im v v tr
khc nhau trong ng tiu ho d dng.
So vi vin nn, vin nang l dng thuc tng i d nghin cu xy dng cng thc.
D trin khai sn xut cc quy m khc nhau, c th s dng cc my ng nang th cng trong
quy m nh hoc cc my ng nang bn t ng v t ng trong quy m sn xut ln.
Vin nang l dng vin t gp phi cc vn sinh kh dng do khi thuc trong nang khng b nn
cht nn vin d r hn vin nn.
12.2. Thnh phn vin nang
12.2.1. V nang
a) Thnh phn cu to
V nang c ch to t nguyn liu chnh l gelatin, cc cht mu, cht to c nh titan dioxyd
v cc cht ph gia khc.
V nang cng c th c ch to bng dn cht cellulose, loi v nang ny t c s dng v
tan km v gi thnh cao.
b) Hnh dng v kch thc
Hnh dng. V nang c hnh thun di, gm hai phn c gi l np nang (cap) v thn nang
(body). Trn thn nang v np nang c g kho np nang khng b tch ri ra trc v sau khi ng
thuc. Mt s nang c hai kho gm mt g kho v mt l. V nang c cung cp trong tnh trng
y np tm, sau khi ng thuc xong s c y np cht.
Kch thc. V nang c sn xut vi nhiu c khc nhau, c nh s t 00 n 5, mi c c
mt dung tch nht nh. Cc c nang thng dng l c s 0, s 1 v s 2.
Bng 12.1. Dung tch cc c nang

Hnh 12.2. V nang rng

Hnh 12.3. Np nang v thn nang:
1. V tr m; 2. ng np tm;
3. ng np sau khi ng thuc.

Hnh 12.4. Nang c g kho

c) Bo qun v nang
V nang cng c hm m khong 13 16%. Hm m ca nang ng vai tr nh mt cht ho do
gi cho nang khng b dn v m bo bn ca v nang. Khi hm m trong v nang thp, v nang s
b dn; khi hm m cao, v nang s b mm. Hm m trong v nang cng nh hng n kch thc v
nang. Cc nghin cu tng quan gia nh hng ca hm m c trong v nang cng v kch thc cho
thy nu hm m trong v nang thay i 1% th kch thuc s thay i 0,5%. S gim hoc tng hm m
c trong v nang khng mang tnh cht thun nghch, nu hm m b mt qu nhiu th s kh c th
phc hi li hm m bnh thng khi c bo qun li iu kin ti u cho v nang (RH 35 50%).
V nang dng cho my ng nang tc cao cng cn phi c bo qun trong iu kin nghim ngt
hn kch thc khng b thay i.
Cc nh sn xut v nang thng ng gi v nang trong bao b kn, chng m tt. Cc v nang s
c tui th cao nu c bo qun trong bao b kn, iu kin nhit trong khong 10 35
o
C v hm
m trong khong 20 60%. Trnh bo qun v nang rng gn ngun nhit, nh sng chiu trc tip.
d) Tiu chun v nang cng
Kch thc: Kch thc ca v nang phi c ch to theo ng tiu chun c th dng c
trong tt c cc my ng nang khc nhau.
tan: V nang khng c tan trong nc nhit 25
o
C trong vng 15 pht v phi tan hoc r
hon ton trong dung dch acid hydrochlorid 0,5% nhit 36 38
o
C trong vng 15 pht.

Hm m v dn ca v nang: Hm m ca v nang rng phi trong khong 13 16%, xc nh
bng phng php sy 105
o
C. dn ca v nang c th c kim tra bng cch bp nh: v nang
khng c v.
Mi: V nang phi khng c thi ra mi l sau khi bo qun trong bnh y kn nhit 30
40
o
C trong thi gian 24 gi.

e) Cc khim khuyt ca v nang
Cc v nang c th c nhng khim khuyt nht nh trong qu trnh sn xut. Cc khim khuyt
ny c chia thnh ba loi, tu theo mc quan trng khc nhau:
Khim khuyt ti hn l nhng khim khuyt c th nh hng trc tip n qu trnh ng thuc
vo nang bao gm: nang qu ngn hoc qu di, v nang b bp, b rn nt, c l hoc bin dng.
C nang Dung tch (ml)
00 0,95
0 0,67
1 0,48
2 0,38
3 0,28
4 0,21
5 0,13
Khim khuyt ln l nhng khim khuyt c th gy nhng hu qu nht nh khi s dng, hoc nh
hng n hiu qu tr liu ca thnh phm vin nang nh: nang b h np, y hai np, thnh nang
mng, hoc nt dc theo thn nang.
Khim khuyt nh l nhng khim khuyt khng nh hng n kh nng tr liu ca thnh phm
m ch nh hng n hnh dng cm quan ca thuc nh v nang b , c m, c bt kh.
12.2.2. Thnh phn dc cht trong vin nang
Dc cht trong nang c th nhiu dng khc nhau, trong phn ny ch trnh by thnh phn c
bn ca hn hp bt thuc v cm thuc ng vo v nang.
Xy dng cng thc cho vin nang
Khi thuc (ht, bt) ng vo nang phi c hai tnh cht c bn l trn chy, tnh chu nn.
Cc thuc tnh ny c th thay i nht nh tu thuc vo thit b ng thuc vo nang.
Khi thuc trong nang nn c hm lng ln hn 10mg, trong trng hp hot cht c hm lng
thp nn iu ch vin nn gi thnh s r hn. Cn lu l cc dc cht c tnh ht m cao c kh
nng lm mm v nang, cc dc cht c tnh kim cao hoc acid cao cng c th lm hng v nang.
tng lu tnh v tnh chu nn ca khi thuc, c th p dng cc phng php xt ht kh hoc
xt ht t.
Kch thc ca ht nn ph hp c th m bo ht chy u vo nang ng thi hn ch c
sai s khi lng thuc trong nang.
Cc t dc thng dng iu ch khi bt gm:
T dc n.
Cc loi t dc n dng trong vin nn nh tinh bt, lactose, dicalci phosphat u c th c
dng trong vin nang. Cc loi tinh bt dp thng nh tinh bt tin gelatin ho, tinh bt phun sy c th
c dng gia tng lu tnh v tnh chu nn ca khi ht. Khi ng nang bng my c vt phn liu,
nn s dng cc loi t dc dp thng gip cc khi thuc khng b ri ra khi vt phn liu di
chuyn t v tr nhn ht n v tr v nang.
T dc trn.
T dc trn gip cho ht chy u. S trn chy ca khi ht hoc bt cn thit cho tt c cc my
ng nang khc nhau. trn chy c bit cn thit trong trng hp ng thuc theo nguyn tc a
phn liu. Cc t dc trn thng dng l Mg stearat, talc, tinh bt bp
T dc chng dnh.
Cc t dc chng dnh va c tc dng lm tng lu tnh ca khi bt (hoc ht) va trnh s kt
dnh ca bt thuc ln cc b mt kim loi. S kt dnh ca bt trn piston ca vt phn liu hoc trn
trc nn ca my hot ng theo c ch a phn liu l mt nguyn nhn dn n sai s khi lng.
T dc r. T dc r c th khng cn thit trong trng hp ng bt khng nn vo nang.
Trong trng hp c xt ht hoc trong trng hp c nn p (my c a phn liu hoc vt phn
liu) th nn c t dc r gip thuc phng thch nhanh. Nn s dng cc t dc siu r c th
chn c c nang nh.
Cht gy thm.
Trong trng hp dc cht x nc, c th thm cc cht din hot nh Na lauryl sulfat, Na
docusat hoc Tween gip b mt tiu phn dc cht thm t nhanh.
12.3. Quy trnh sn xut thuc vin nang cng

Hnh 12.5. S tm tt quy trnh sn xut vin nang cng
ng thuc vo nang
Trong trng hp iu ch mt lng nh vin nang dng cho mt s bnh nhn hoc th
nghim lm sng cc thuc mi, khi thuc c th c ng vo nang bng tay (khng dng thit b).
Trong sn xut c th s dng cc my ng nang th cng, bn t ng v my ng nang t ng
tu theo quy m sn xut khc nhau.
12.4. Cc my ng nang thng dng
12.4.1. My ng nang th cng
Trong sn xut quy m nh, c th dng cc my ng nang th cng. My ng nang th cng c
nhiu kch c v nng sut khc nhau:
Loi ng 24 nang/ln c cng sut khong 2000 vin/ngy.
Loi ng 150 nang/ln c cng sut khong 200 vin /gi.
Loi ng 300 nang/ln c cng sut khong 5000 vin /gi.
Nguyn l ng thuc vo nang.
Cc v nang c xp bng tay vo khay mang nang. Cc khay mang nang l cc tm kim loi c
cc l vi ng knh va cho thn nang qua. Khay c lp vo my, trn my c cc l c v tr
tng ng vi cc l ca khay mang nang v c ng knh va kht vi thn nang. Cc l ny c g
kho gi li than nang khi khay mang nang c nng ln.
Tnh trn chy ca khi bt thuc l yu t quan trng nht m bo s ng nht khi lng.
Cc my ng nang c th c dng ng bt thuc, ht cm, vi ht, vi nang.
11.4.2. My ng nang bn t ng v t ng
Cc my ng nang bn t ng v t ng u c mt c ch hot ng ging nhau, gm cc giai
on:
Chnh hng nang. Cc v nang c vo phu mt cch ngu nhin, cc nang s ri vo cc
khe phn cui phu tip liu di chuyn theo tng hng dc vi chiu di chuyn khng nht nh, c
th v thn nang i trc hoc np nang i trc, sau khi ra khi rnh nh hng, cc v nang s c
y hai ln vi tm kim loi thit k c bit, cc v nang s xoay u phn thn nang lun lun i
trc.
M np nang. Cc v nang c sp xp vo trong cc a mang nang (hoc cc bush) nh lc ht
ca mt h thng chn khng. Cc a mang nang c kt cu gm hai phn, phn trn c kch thc va
kht vi np nang, phn di c kch thc va kht vi thn nang (phn di) v np (phn trn).
Thao tc np thuc vo nang c thc hin bng cch gt
khi bt thuc ngang qua thn nang. Sau khi ng thuc, khay
mang np c lp tr li v c p cht bi mm nn pha trn
np nang v cc thanh kim loi phn di thn nang y np
nang.
Cc khay mang nang c nng ln a ton b vin nang
c ng thuc ra ngoi.
Do s ng thuc vo nang c thc hin ch yu bng thao
tc gt lng thuc trong nang va ngang bng ming ca
nang, nn cn phi tnh ton c th t c vin c hm lng
mong mun khi ng mt lng bt thuc va bng dung tch ca
v nang (lng thuc c tnh ton theo t trng biu kin).
Mt s my th cng c mm nn thuc vo nang, tuy nhin
rt kh chun ho thao tc nn nn d mc sai s khi lng.

Hnh 12.6. My ng nang th cng

Hnh 12.7. S cc cng on chnh hng v m np nang trong cc my
ng nang t ng v bn t ng
ng thuc vo nang: c nhiu nguyn l ng thuc vo nang, c trng cho mi loi my.
Cc a mang np v thn nang s khp li vi nhau y np nang. giai on ny cc thanh
kim loi trn s di chuyn t di ln ng cht np nang, ng thi y nang ng thuc v y
np ra.
a) My ng nng bn t ng
Nguyn l ng thuc vo nang ca my ng nang bn t ng.
Khi thuc ra khi phu tip liu nh mt vt p bt c trong phu. Vt p bt ch a bt ra khi
phu ch khng p khi bt vo nang. S ng thuc vo nang ch yu da vo nguyn tc th tch.
Khi lng thuc ng vo nang c kim sot bi tc quay ca mm mang nang.
trnh sai s khi lng, khi bt phi c trn chy tt c th chy vo nang vi mt tc
n nh. Thnh phn ca khi bt thuc nn c thm cc t dc iu ho s chy v t dc chng
dnh nh talc, Mg stearat hoc acid stearic
Chu trnh ng nang gm cc giai on sau:
Nang rng c cp vo phu tip liu: Giai on np nang ngu nhin
Nang i vo cc ng dn nh hng: Cc v nang chuyn ng tnh tin theo nhng hng dc.
V nang c chnh hng: Tt c cc v nang chuyn ng theo mt chiu, thn nang i trc,
np nang i sau. S chnh hng trn c s s khc nhau v ng knh ngoi gia phn np nang v
phn thn nang.
Np nang: V nang c np vo cc vng khay. Vng khay c cu to gm hai vng ring bit
chng kht ln nhau, trn vng c cc l mang nang, l phn vng khay trn c ng knh bng
ng knh ngoi ca np nang, l phn vng khay di c ng knh bng ng knh ngoi ca
thn nang.
Tch nang: Khi vng khay c quay, chn khng mt di vng mang nang s ht phn thn
nang xung vng di trong khi np nang li vng trn.
ng thuc: Hai phn ca vng khay np nang c tch ra, vng cha np ra bn cnh, vng
cha thn nang c t trn mt mm quay c th iu chnh tc nm di phu bt, trong phu
c vt p bt hnh mi khoan. Sau mt hoc nhiu vng quay ca vng khay, phu bt c nhc ra.
ng np: Hai phn ca vng np nang c nhp li chng kht ln nhau v t vo pha trc
vng inh ng np v tm y. V tr vng ng np c th quay quanh trc mt gc 180
0
, p sut hi
c cung cp cho vng ng y thn nang vo np nang v tm y gi np nang nguyn
v tr.
Tho nang: tho nang, p sut c x, tm ng c a v v tr ban u v nang c tng
ra ngoi qua phn trn ca khay i theo mng trt ra ngoi.

Hnh 12.8. My ng nang bn t ng

Hnh 12.9. Vt p bt ca my ng nang bn t ng
b) My ng nang t ng
C tnh chu nn khi thuc khng b ri ra v ri xung khi vt phn liu di chuyn t phu
tip liu sang v tr ng nang.
C lu tnh tt khi thuc trong phu tip liu lun lun cao hn v tr ca piston trong vt phn
liu.
C kh nng chng dnh khi thuc c th tch ri khi vt phn liu khi piston nn xung.
Nn c t trng khi trung bnh, khi bt c t trng khi thp s cha nhiu khng kh, nn tnh
chu nn s thp dn n khuynh hng t ri ra tng t nh trng hp t chm ca vin nn.
Kiu ng thuc bng vt phn liu (Dosator).
Cc my thng dng: MG2, Macophar, Pedino, Seteco, Zainasi.
Nguyn l ng thuc vo nang.
Vt phn liu ca h thng c cu to l mt ng hnh tr, bn
trong c mt piston c th di chuyn c. cao ca piston c th
iu chnh c th ly c mt th tch bt nht nh (tng t nh
iu chnh th tch bung nn trong my dp vin). Chiu cao ca
khi bt chy ra t phu tip liu phi lun lun cao hn chiu cao
ca piston, vt phn liu c th ly lng bt, khi vt phn liu
cm vo khi bt trong phu tip liu, piston s nn nh khi thuc
dnh thnh mt khi. Vt phn liu sau ri khi phu tip liu v di
chuyn sang v tr nang rng m np v piston s p khi bt thuc
vo nang.
Khi lng thuc trong nang c kim sot bi hai yu t:
Chiu cao ca piston trong vt phn liu.
Chiu cao ca khi bt thuc ti v tr vt phn liu nhn bt.
Bt thuc ng vo nang phi c nhng tnh cht sau:

Hnh 12.10. Vt phn liu (Dosator)

Hnh 12.11. Nguyn l ng thuc ca vt phn liu (dosator)
(1) Vt phn liu i xung khi bt; (2) Bt c nn thnh khi cng; (3) Vt phn liu mang theo khi
bt xoay qua v tr v nang; (4) Vt phn liu i xung, ng khi thuc vo v nang;
(5) Thn nang di chuyn sang v tr ng np; (6) Vt phn liu i ln v xoay sang phu tip liu
ng vi ht hoc vi nang bng my c h thng
vt phn liu. Cu to ca vt phn liu tng t nh
trong trng hp ng bt thuc nhng my c
gn thm h thng ht chn khng. Khi vt phn
liu di chuyn vo khi vi ht, h thng chn khng
s hot ng ht vi ht hoc vi nang vo lng
ng, ht tha s c gt ra trc khi di chuyn
sang v tr nang rng. Khi vi ht c trong phu tip
liu phi khng c cha bt mn trnh lm tc
h thng ht chn khng.
Ngoi ra, my kiu vt phn liu c th gn
thm cc ph tng thay th ng cht lng, ng
vin nn, hoc ng hn hp vin nnvi ht, vin
nncm,
Tu theo mc hin i, cc my c th c
nng sut t 90.000 n 150.000 vin/gi.

Hnh 12.12. Chuyn ng ca vt phn liu

Hnh 12.13. Nguyn l ng vi ht vo nang ca vt phn liu
(1) Vi ht c ht vo vt phn liu nh chn khng; (2) Vt phn liu i ln mang theo vi ht.
(3) Gt ht tha; (4) Vt phn liu i xung n v tr thn nang; (5) ng vi ht vo v nang.
(6) Vt phn liu i ln v di chuyn sang v tr phu tip liu.
Kiu ng thuc bng a phn liu (dosing disk)
Cc my thng dng: Bosch
Nguyn l hot ng.
Khi bt thuc sau khi chy ra khi phu tip liu s c tri thnh mt lp mng vi mt b dy
n nh trn mt a quay c gi l a phn liu. a phn liu c l c ng knh tng ng vi
ng knh trong ca v nang. Khi a xoay ngang qua v tr ng thuc, khi bt s c nn to
thnh mt khi cng. S nn c th c thc hin t mt n nm ln trc khi khi thuc c ng
vo nang.
Lng thuc ng vo nang ph thuc ba yu t chnh:
dy ca khi bt thuc c trn a phn liu.
dy ca a phn liu.
Lc nn ca piston.
dy ca khi bt thuc trn nang c iu chnh bng cch iu ho s chy ca thuc trn a
phn liu. c th c c mt chiu cao n nh, phu tip liu c thit k mt h thng o bn
trong gip ht chy u v mt u o (sensor) ng phu tip liu trong trng hp b dy ca
lng bt thuc qu cao.
m bo c ng nht khi lng, iu quan trng nht l khi bt phi c lu tnh cao, c
tnh chu nn nht nh c th nn c thnh khi v cc tiu phn bt khng c kt dnh thnh
khi trn piston nn.
Kiu my ny c th dng ng cc vi ht hoc vi nang vo nang. Trong trng hp ny, h
thng nn s khng hot ng cc lp bao ca vi nang khng b rch v cc vi nang khng b bin
dng.

Hnh 12.14. Nguyn l ng thuc ca my ng nang c a phn liu
Chu trnh ng thuc vo nang gm nhng cng on sau:
Cp nang, chnh hng nang, np nang vo l khun bng h thng ht chn khng.
Tch nang
Sau khi tch nang, phn mang np nang s di chuyn vo bn trong phn c thn nang khng b
cn tr bi gi mang np v sn sng nhn thuc.
Trm phn liu cho vin nang cha vi ht, vin nn hoc vin bao.
Trm phn liu cho bt hoc cht lng.

Hnh 12.15. H thng nn thuc v a
phn liu ca my ng nang t ng

Hnh 12.16. S m t quy trnh ng thuc vo nang
ca my hot ng theo nguyn tc a phn liu
Trm phn liu cho vi ht, vi nang.
Trm loi nang hng, ti v tr ny cc nang khng c m np hoc khng c t ng v tr
s c y ra khi my.
Trm xp hng thng np nang vi thn nang.
Phn mang np nang quay tr li v tr ngay pha trn thn nang sn sng ng np.
y np cho vin nang c ng thuc.
Cc vin nang c y ra khi my.
Cc mm mang nang c ht bi lm sch trc khi bt u chu trnh mi.
Cc my ng nang kiu a phn liu c nng sut rt cao c th ln n 2000 vin/pht.
12.5. Hon chnh vin nang
Sau khi ng thuc vo nang, cc vin nang cn c loi bi v nh bng trc khi ng gi. Tu
theo iu kin trang thit b c sn, c th p dng cc phng php sau:
Loi bi bng phng php th cng. C th loi bi bng cch lau cc v nang vi vi cotton, vi
gc c th tm mt t du vo vi sau khi lau vin c bng.
Loi bi v nh bng trong ni bao. Ni bao c l c h thng thi v ht kh rt mnh, c th
dng loi bi trn vin nang d dng, c th lt vi trong ni nh bng vin trong qu trnh loi
bi.
Loi bi bng h thng lau v nh bng vin. Thit k ca h thng gm mt b phn lau vin
dng bn chi c trong mt ng hnh tr, h thng c ni vi mt my ht bi. Cc vin s c lau
sch bi v nh bng khi i qua lng ng.
12.6. Kim tra kim sot trong qu trnh sn xut
Kim tra tnh cht ca ht: sn phm t c ng u khi lng, ht phi c kch thc
v phn b kch thc ht ph hp trnh qu trnh phn lp khi my ng nang vn hnh. Lu tnh
ca ht l mt thng s quan trng i vi tt c cc thit b ng thuc vo nang. Cc phng php
dng trong vin nn u c th c p dng nh gi lu tnh ca khi bt, ht dng ng nang.
Khi lng trung bnh vin cn phi c kim tra thng xuyn trong qu trnh ng nang, my
vn hnh cng nhanh cng phi kim tra cht ch hn. S kim tra c th thc hin nhanh bng cch cn
c v nang (phi bit trc khi lng trung bnh ca v nang).
Hnh dng cm quan ca vin nang nn c kim tra ton b, v c th c nhng trng hp v
nang khim khuyt nhng my khng loi c, hoc c th c nhng khim khuyt xy ra ngay trong
qu trnh ng thuc vo nang bng my.
Trong cng ngh sn xut vin nang hin i, cc vin sau khi c ht bi v nh bng, s c
chuyn ln mt h thng bng ti. Khi di chuyn trn bng ti, cc vin va di chuyn va xoay nhn
vin c th kim sot ton b hnh dng cm quan tt c cc vin nang. Mt vi my hin i nh h
thng hon thin vin nang ca hng ParkeDavis, c thm h thng cn kim tra t ng loi cc
vien nang nm ngoi gii hn cho php.

Hnh 12.17. Dy chuyn ng thuc vo nang theo quy trnh khp kn
12.7. Kim tra cht lng vin nang
Cc ch tiu cht lng ca vin nang bao gm nh tnh, nh lng, ng u hm lng,
ng u khi lng, thi gian r v tc ho tan hot cht.
ng u khi lng ch c tnh trn lng thuc c trong nang, nn phi tr khi lng v
nang ca tng vin trc khi tnh ton.
Th nghim ho tan ca vin nang thng c thc hin bng thit b gi quay vin nang
khng ni ln trong qu trnh th. Trng hp dng thit b cnh khuy, vin nang cn c lng vo
trong mt ng kim loi gi cho vin chm di y.
Trng hp th r, phi dng a t trn vin vin lun lun nm trong mi trng th. Vin
nang cng phi r trong thi gian khng qu 30 pht.

TI LIU THAM KHO
1. Leon Lachman, Herbert A.Lieberman, Josept L.Kanig. The Theory and Practice of Industrial
Pharmacy, Lea v Friger, Philadenphia, 1986.
2. Brian E.Jones, Capsule, Hard, in Encyclopedia of Pharmaceutical Technology, Marcel Dekker,
1990.
3. Ronnie Millender, Capsule shell composition and manufacturing, in Multiparticulate Oral Drug
Delivery, Marcel Dekker, 1994.
4. K.Ridway, Hard capsule: Development and Technology, The Pharmaceutical Press, 1987.

CU HI LNG GI
Chn cu tr li ng nht
1. Ngoi gelatin, nguyn liu no cn c s dng lm v nang cng:
a) Gm Arabic; b) Shellac;
c) Dn cht cellulose; d) Dn cht methacrylic.
2. Hm m trung bnh ca v nang cng:
a) 4 7%; b) 7 10%;
c) 10 13%; d) 13 16%.
3. iu kin bo qun v nang cng
a) Nhit 4 25
o
C m tng i 20 60%;

b) Nhit 10 25
o
C m tng i 30 70%;

c) Nhit 20 30
o
C m tng i 20 60%;

d) Nhit 10 35
o
C, m tng i 20 60%.

4. Tiu chun v tan ca v nang cng:
a) Tan hoc r hon ton trong nc 37
o
C trong vng 15 pht;

b) Tan hoc r hon ton trong dung dch m pH 6,8 nhit 37
o
C trong vng 15 pht;

c) Tan hoc r hon ton trong nc nhit phng trong vng 15 pht;
d) Tan hoc r hon ton trong dung dch acid hydrochlorid 0,5%/ 37
o
C trong vng 15 pht.

5. V nang b khim khuyt ti hn:
a) Khng th dng ng thuc vo nang;
b) ng thuc vo nang c, nhng cht lng vin nang thnh phm khng t;
c) Khng nh hng n cht lng v hiu qu tr liu ca vin nang thnh phm;
d) Ch nh hng n cm quan ca dng thuc.
6. Trong sn xut thuc vin nang cng, nn s dng cc loi t dc dp thng :
a) Trnh hin tng ht m ca khi thuc trong nang;
b) Tng tnh chu nn ca khi ht;
c) Vin nang thnh phm s r nhanh;
d) Tng tui th ca ch phm.
7. Yu cu quan trng nht ca khi ht khi ng thuc vo nang theo nguyn tc th tch:
a) Tnh chu nn cao;
b) Hm m rt thp;
c) Lu tnh cao;
d) C th tch biu kin ph hp vi c nang c chn.
8. Nguyn tc ng thuc vo nang bng my t ng c vt phn liu (Dosator):
a) Nn ht thnh khi trc khi cho vo nang;
b) ng theo th tch nang;
c) Nn nhiu ln c mt khi thuc tht cng;
d) Cc nguyn tc trn u khng ph hp.
9. Yu cu quan trng nht ca khi ht khi ng thuc vo nang bng my t ng c vt phn liu
(Dosator):
a) Tnh chu nn cao; b) Hm m rt thp;
c) Lu tnh cao; d) a v b ng;
e) a v c ng.

Bi 13
CNG NGH BO CH THUC TIM

13.1. i cng
13.1.1. Cc hnh thc phn phi thuc tim
Thuc tim liu nh c phn phi di cc hnh thc:
Dung dch sn sng tim.
Hn dch sn sng tim.
MC TIU
1. Tnh ton c cng thc pha ch.
2. Trnh by c nguyn tc b tr c s pha ch, tiu chun phng sch, nguyn tc x l, cung
cp khng kh cho phng sch.
3. Trnh by c phng php m bo v trng ch phm tim.
4. Trnh by c quy trnh cng ngh pha ch:
Dung dch tim, tit trng sn phm
Bt pha tim theo k thut iu ch v trng
5. Trnh by c nguyn tc v cch vn hnh cc thit b:
My ct nc
H thng ra ng v ng ng bng chn khng.
My ng ng v hn ng.
Ni hp tit trng.
Nh tng tim.
Sn phm dng rn sn sng kt hp vi dung mi to thnh dung dch ngay trc khi dng.
Sn phm dng rn sn sng kt hp vi cht dn to thnh hn dch ngay trc khi dng.
Thuc tim liu ln (100 ml) gm cc loi:
Dung dch tim truyn.
Nh tng tim truyn.
Ngoi ra, c mt s dung dch yu cu cht lng nh thuc tim truyn:
Dung dch ra, thm phn phc mc.
Dung dch chng ng bo qun mu.
13.1.2. Cc yu cu v cht lng thuc tim
Cc yu cu c bit i vi thuc tim:
trong sut (i vi dung dch)
pH ph hp
ng trng
V trng
Khng c cht gy st
Hm lng dc cht chnh xc
Cc yu cu c thc hin trong qu trnh:
Xy dng cng thc bo ch: pH, ng trng
Pha ch sn phm: trong sut, hm lng chnh xc, v trng, khng c cht gy st.
13.2. X l cng thc pha ch
13.2.1. Pha ch theo cng thc c sn
Ly ng loi v lng dc cht c trong cng thc.
Tnh li lng dc cht theo t l m hoc t l nc kt tinh c trong cng thc:

Trong :
+ m: Khi lng nguyn liu cn phi cn
+ a: Khi lng ca nguyn liu l thuyt tnh theo lng dung dch cn pha
+ b: m ca nguyn liu
13.2.2. Tnh ton lng dc cht, dung mi, th tch pha ch theo nng yu cu
a) Nng phn trm
Trng lng/ th tch (g/100ml)
Trng lng/ trng lng (g/100g)
Th tch/ th tch (ml/100ml)
Th tch/ trng lng (ml/100g)
V d: Pha ch 1000ml dung dch magnesie sulfat 5% (5g/100ml).
Pha ch 500ml dung dch sodium chloride 0,9% (0,9g/100ml).
b) Lng dc cht trn mt n v th tch
Pha ch 1000ml dung dch c atropin sulfat 600g/ml.
Pha ch 1000ml dung dch c ephedrin hydrochlorid 30mg/ml.
c) Nng ng lng mEq/l (miliequyvalent)
n v mEq/l thng c dng khi pha ch dung dch b cht in gii cho huyt tng.
Lng mui cha 1mEq ca 1 ion c tnh bng cng thc:

V d: Mui NaCl (M = 58,5)

Nh vy trong 58,5mg NaCl c cha 1 mEq Na
+
v 1 mEq Cl

Cng thc chuyn i t mg sang mEq v ngc li:

V d:
Cn b cho mu cho mt lng cht in gii l 63 mEq Na
+
, 17 mEq K
+
v 150 mEq Cl
. Tnh
cng thc pha ch?
Mt dung dch cha 409,5mg NaCl trong 1000ml. Tnh s mEq Na
+
v Cl
(bit NaCl = 58,5)?

C bao nhiu mEq Mg
++
trong 10ml dung dch 50% Magnesie sulfat tim (MgSO
4
.7H
2
O = 246)?

Mt chai dung dch tim NaCl cha 3 mEq/ml, hm lng ca dung dch l bao nhiu? (NaCl =
58,5)
d) Nng mol/l v mmol/l
i vi phn t: 1 milimol (mmol) l trng lng tnh bng mg tng ng vi khi lng phn t.
i vi ion: 1 milimol (mmol) l trng lng tnh bng mg tng ng vi khi lng nguyn t.
V d: 1 mmol NaCl = 58,8mg
1 mmol NaCl c 1 mmol Na
+
v 1 mmol Cl

Cng thc chuyn i:
V d:
Tnh s mmol ca dextrose v Na
+
trong 1 lt hn hp NaCl 0,9% v dextrose 5%? (PTL glucose:
180,2 v NaCl: 58,5)
Tnh s mmol ca Mg
++
v Cl
trong 1 lt dung dch 2% MgCl

2
(MgCl
2
.6H
2
O: 203)

Tnh s lng ca mui cn thit pha ch dung dch in gii sau:
Na
+
12 mmol

K
+
4 mmol

Mg
++
6 mmol

Ca
++
6 mmol

Cl
40 mmol

Nc ct va 1000ml
13.3. C s pha ch thuc tim
13.3.1. Yu cu chung
Khu vc pha ch thuc tim thng c cc b phn vi cc chc nng sau:
Khu vc x l chai l, ng tim.
Phng v sinh, thay .
Kho nguyn liu bao b.
Phng cn.
Phng pha ch.
Phng ng ng, hn ng.
Phng hp tit trng.
Phng soi, in.
mg/l = W x M

W: s mg mui cha 1 mmol ca ion yu cu
M: s mmol/l
TL/ TT: trng lng/th tch
Phng ng gi, hon chnh sn phm
Cc b phn phi c b tr hp l, theo nguyn tc mt chiu chng nhim v nhim
cho.
m bo s cch ly duy tr mc sch bng ca la hoc cht gi.
Lu cc lung di chuyn ring cho cc i tng: nhn vin; nguyn liu bao b, bn thnh
phm; thnh phm v d phm
S b tr i vo phng pha ch v ng ng trong quy trnh pha ch vi s tit trng sn phm cui
cng c th theo s sau:

Hnh 13.1. Phng pha ch thuc tim c tit trng sn phm cui cng
13.3.2. Phng v khu vc sch trong pha ch cc ch phm v trng
Theo quy tc thc hnh sn xut tt ca T chc Y t Th gii (GMP ca WHO), cc ch phm v
trng phi c sn xut trong phng sch hoc khu vc sch. l khu vc c quy nh gii hn
mc nhim tiu phn v vi sinh vt sng nhm gim nguy c nhim tiu phn v vi sinh vt trong
tt c nhng giai on ca qu trnh sn xut, cho php thu c ch phm v trng. Phng sch c
phn chia thnh bn cp vi cc mc gii hn v tiu phn v vi c khc nhau nh trong bng 13.1,
bng 13.2 v bng 13.3.
Bng 13.1. Mc nhim cc tiu phn (phng c ngi hoc khng c ngi)
theo GMP ca WHO

Cp
sch
S lng ti a cc tiu phn c trong 1m
3
khng kh

Trng thi ngh Trng thi ang hot ng
Kch thc tiu phn Kch thc tiu phn
0,5 5,0m > 5,0m 0,5 5,0m > 5m
Bng 13.2. Gii hn s nhim vi sinh vt ca phng sch ang hot ng
theo GMP ca WHO
Bng 13.3. Cp sch theo GMP ASEAN

Yu cu cp sch cho phng pha ch v ng ng ty thuc vo quy trnh pha ch v phng
php tit trng ca sn phm.
a) Quy nh iu kin sn xut ch phm v trng c tit trng sn phm cui cng theo GMP WHO
A 3.500 0 3.500 0
B 3.500 0 350.000 2.000
C 350.000 2.000 3.500.000 20.000
D 3.500.000 20.000 Khng quy nh Khng quy nh
Cp
sch
S VSV
trong 1 m
3
khng
kh (CFU/ m
3
)
t a thch
ng knh 90mm
(CFU/4 gi)
a thch tip xc
ng knh 55mm
(CFU/a)
Phng php
nhng gng 5
ngn (CFU/gng)
A < 3 < 3 < 3 < 3
B 10 5 5 5
C 100 50 25 khng p dng
D 200 100 50 khng p dng
Cp
sch
S lng tiu phn ti a trong 1m
3
khng kh

S lng VSV
trong 1m
3

0,5 5m > 5m
I 3.500 Khng 0
II 350.000 2.000 100
III 3.500.000 20.000 500
IV >3.500.000 >20.000 >500
Giai on pha ch Yu cu c s trc khi tit trng
iu ch dung dch c lc v
tit khun
Cp C: cho sn phm d nhim vi sinh vt
Cp D: nu dung dch c lc sau
ng thuc (thuc tim liu
ln hoc nh)
Cp C
Cp A trong khu vc C: i vi sn phm c nguy c nhim
cao nh l ming rng
Phn ln cc thuc tim c tit trng sn phm cui cng phi c pha ch trong iu kin t nht
l cp sch D nhm gim thiu s lng vi sinh vt v tiu phn thch hp cho vic lc v tit
trng.
Khi c nguy c nhim vi sinh vt do c tnh thun li cho s pht trin hoc phi gi lu trc khi
tit trng hoc khng c pha ch trong cc bnh kn phi pha ch thuc tim trong mi trng sch
cp C.
Cng on ng thuc phi c thc hin mi trng sch cp C tr ln, tuy nhin khi c
nguy c cao nhim t mi trng nh chai l ming rng hoc phi h trong vi giy trc khi
ng nt, qu trnh ng thuc tim phi thc hin trong mi trng sch cp A vi mi trng xung
quanh l cp C tr ln.
b) Quy nh iu kin sn xut ch phm theo k thut pha ch v trng
Cc thnh phn bao b sau khi ra phi c x l mi trng sch cp D tr ln.
Vic cn v gi nguyn liu v cc thnh phn khc phi c tin hnh trong mi trng sch cp
A vi mi trng xung quanh l B, tr khi sau khi pha ch cc thnh phn ny c tit trng hoc
dung dch c lc tit khun.
Vic pha ch phi c tin hnh trong khu vc sch cp A trong mi trng xung quanh l B,
tr khi dung dch c lc tit khun sau .
Qu trnh ng thuc phi c tin hnh trong mi trng sch cp A trong mi trng xung
quanh l B.
Nu c s di chuyn cc sn phm cn h, nh trong ch bin bt ng kh, phi c tin hnh
trong mi trng sch cp A trong mi trng xung quanh l B.
13.3.3. Kim sot mi trng v cung cp khng kh cho phng hoc khu vc sch
Khi hot ng khu vc sch d b nhim do:
S tun hon v di chuyn ca khng kh
S xm nhp ca khng kh bn ngoi
S nhim do hot ng ca ngi, quy trnh pha ch
duy tr mc sch, GMP quy nh cung cp khng kh sch lin tc thay th khng kh
nhim. Kh nng duy tr mc sch tu lu lng v cch thi khng kh vo.
Giai on pha ch Tiu chun yu cu
Gi cc vt liu v khun Cp A trong khu vc loi B
Cp C: nu dung dch c lc v trng trong
quy trnh sn xut
iu ch dung dch Cp A trong khu vc loi B
Cp C: nu c lc tit khun
ng thuc (th tch nh hoc ln) Cp A trong khu vc loi B

A. u vo E. Gin nng I I. HEPA
B-K. B gim sc F. Gin ngui J. HEPA (nu cn)
C. Tin lc (30% G. Gin nng II
D. Tin lc 85% H. Qut gi
H thng x l khng kh vi lc HEPA
Hin nay lc HEPA (High Efficiency Particulate Air Filter) thng c dng lc khng kh
cung cp cho phng sch.
Mng lc HEPA c ch to t nguyn liu dng si nh si cellulose, si thu tinh, si amiant v
s xp. Mng lc HEPA c phn loi da trn kh nng ngn cn cc tiu phn c kch thc 0,3m
c trong lung khng kh.
Mng lc HEPA chun lc c 99,97% tiu phn, mng HEPA siu lc c th lc c 99,99% s
tiu phn c kch thc 0,3m.
duy tr v ko di tui th ca mng lc, khng kh trc khi i vo khu vc sch phi i qua 2
mng lc:
Mng tin lc nhm loi b cc tiu phn bi c kch thc ln v c tc dng bo v mng lc
chnh.
Khng kh sau khi i qua mng tin lc s c nn qua mng lc HEPA chnh c kch thc l lc
t 0,2 n 0,25m v i vo khu vc pha ch.
C nhiu cch b tr, thit k lc HEPA cung cp khng kh cho phng hoc khu vc pha ch
sch:
M hnh thi kh mt chiu (hnh 13.2)
M hnh thi kh khng theo mt chiu (hnh 13.3)
M hnh thi kh kiu hn hp (hnh 13.4)
Cc hnh thc thit k ny quyt nh tc thng kh do nh hng n sch. M hnh thi
kh kiu hn hp cho php tit kim chi ph x l khng kh m vn duy tr khu vc sch t theo yu
cu.
Ngoi ra c th pha ch trong khu vc sch hn ch bng cc t khng b nhim t bn ngoi hoc
hon ton c lp cch ly vi mi trng ngoi (hnh 13.5, 13.6, 13.7). Hnh thc ny rt tin li khi pha
ch cc hn hp v trng ti bnh vin.

Hnh 13.2. M hnh thi kh song song
theo mt chiu

Hnh 13.3. M hnh thi kh
khng theo mt chiu

Hnh 13.4. M hnh thi kh kiu hn hp:
kiu mt hng khu vc c bit v
khng theo mt hng mi trng xung quanh

Hnh 13.5. Bung thi kh song song
mt hng theo phng nm ngang

13.4. m bo s v khun ca thuc tim
Ty theo tnh cht ca dc cht, cu trc v hnh thc ca cc dng thuc tim vic bo m tiu
chun v trng c th c thc hin bng cch tit khun sn phm hoc iu ch theo k thut pha
ch v trng.
13.4.1. Tit khun sn phm
Tit khun bng nhit: tt nht l tit khun bng nhit cng on cui khi thuc tim c
ng gi vo bao b cui cng vi iu kin cc thnh phn trong cng thc chu c nhit .
Tit trng bng nhit m: ch thch hp cho cc thuc tim chu c m v cc dung dch s dng
dung mi l nc.
Tit trng bng nhit kh: thch hp vi thuc tim lng khng phi l nc hoc sn phm bt kh.
Tit khun bng cch lc: mt s dung dch hoc cht lng khng th tit trung trong bao b cui
cng c th c lc qua lc v trng vi kch thc l lc ti a l 0,22m vo bao b c tit
trng trc, cn lu mng lc khng th loi virus v nm mycoplasma. Cn xem xt kt hp quy
trnh lc vi x l bng nhit mc thch hp v thc hin cc bin php tng t nh trong k
thut iu ch v trng.
13.4.2. iu ch theo k thut pha ch v trng
K thut pha ch v trng c ng dng trong cc trng hp khng th tit khun sn phm bng
nhit, bng cch lc hoc dng ho cht m bo tiu chun v trng ca ch phm. Nguyn tc
chung trong k thut pha ch v trng l tit khun ring l tng thnh phn tham gia trong pha ch v
Hnh 13.6. Bung thi kh song song
mt hng theo phng thng ng
Hnh 13.7. Bung c lp, sch, c x l
khng kh ra

Hnh 13.8. H thng bung c lp pha thuc tim
phi phn phi trong mi trng v khun c kim sot cht ch.
Nhm duy tr s v trng ca cc thnh phn v ca thuc tim trong qu trnh pha ch cn ch :
mi trng, nhn vin pha ch, cc b mt tip xc quan trng, s v trng ca bao b, nt, qu trnh di
chuyn, thi gian lu gi cc sn phm trc khi ng chai, l, lc v trng
C th cn thc hin:
Nguyn liu c tit trng trc theo phng php ph hp.
Dng c c tit trng.
Kim sot mi trng sch mc cao: cp A.
Bnh cha c tit trng trc.
K thut pha ch thch hp, m bo v sinh v trng c thc hin bi nhn vin c hun
luyn.
Tu theo cu trc v dng c th, cc giai on pha ch v tit trng thuc tim c th c trnh
by tm tt theo s sau:

Cc giai on pha ch v m bo v trng cho ch phm
13.5. Quy trnh k thut pha ch thuc tim
13.5.1. Quy trnh x l chai l, ng tim
13.5.2. Quy trnh iu ch dung dch tim v tit trng sn phm
13.5.3. Pha ch thuc tim theo k thut v trng
* i tng
Cc hn dch tim
Cc nh tng tim
i tng Thao tc k thut Ni dung kim sot
ng tim, chai l X l

Ra ngoi

Ra trong

Sy kh
Tit trng

Nhit
Thi gian
Cng thc Tnh ton lng dc cht,
t dc
Kim tra cng thc, tnh ton
Dc cht
T dc
Cn, ong

Kim tra cn ong
Dung mi Ho tan

Kim tra th tch pha ch
Dung dch Lc

trong, hm lng

ng ng, hn ng Th tch ng ng

Hp tit trng

Nhit
Thi gian
ng thuc Soi trong, kn u hn, th tch
ng

In nhn

ng hp

Thnh phm Bit tr

Nhp kho
Kim tra theo tiu chun quy nh
Cc thuc bt pha tim
Ngoi ra cc dung dch tim khi tit trng bng cch lc cng cn p dng cc nguyn tc ca k
thut iu ch v trng.
Quy trnh cng ngh vi bt pha tim c th nh sau:
13.6. Cc yu cu kim nghim i vi sn phm tim
Dc in Vit Nam quy nh cc ni dung kim nghim thnh phm
1. trong v kch thc tiu phn
Dung dch: kim tra trong
Hn dch: khng ln nhn ht to. Xc nh kch thc tiu phn
2. Mu sc
3. V trng
4. Cht gy st v ni c t: kim nghim khi th tch n liu 15ml,
5. pH v cc ch s khc:
Dung dch nc: kim tra pH
Dung dch du phi xc nh ch s acid, ch s iod, x phng ho
6. Th tch
7. Chnh lch khi lng (dng bt tim)
Cng thc Tnh ton s lng Kim tra cng thc
Dc cht
T dc
Cn, nghin, tn, x l v trng

Kim tra cn, kim tra iu kin
Bt n Phi hp, trn

Hm lng, ng nht
Bt kp Phn phi

Trng lng
Chai cha dc cht ng np

Dn nhn

ng hp

Thnh phm Bit tr

Nhp kho
Kim nghim theo tiu chun
8. nh tnh
9. nh lng
13.7. Cc trang thit b c bn trong sn xut thuc tim
1. My ct nc
2. H thng ng ng v ra ng bng chn khng
3. My ng thuc v hn ng
4. Ni hp

Hnh 13.9. S my ct nc

Hnh 13.10. My ct nc c tc ng kp

Hnh 13.11. Nguyn tc ng tng ng

Hnh 13.12. S my ng ng tim tng ng

Hnh 13.13. S my tit trng bng hi nc
a) p k chnh; b) B phn tch ri, c) Van gim p, d) ng cung cp kh cho v ngoi,
e) ng cung cp kh cho bung tit trng; f) B lc kh, g) p k o p sut trong lp v,
h) p k o p sut bung tit trng, i) L thng kh cho lp v, j) Bm chn khng, k) ng x thng vi lp v,
l) ng x cho bung tit trng, m) L cha nhit k, n) Nhit k c trc tip, o) B phn ghi nhit , p) B lc,
q) Van kim tra, r) B iu chnh nhit , s) ng nhnh, t) ng thot hi nc, u) Van ng bng nc.

TI LIU THAM KHO
1. D.G. Chapman. Clean room for the production of pharmaceutical products, Pharmaceutical
Practice, 1998, p.222 235.
2. Jamis. C Boylan, Alan L. Fites, Steven L. Nai, Parenteral products, Modern Pharmaceutics, third
edition, 1995, p. 441487.
3. A. Le Hir. ng Tim, Gin yu Bo ch hc, tr. 267283.

P N
Bi 1
1. b) Gia tng v bnh tt. d) Li nhun.
2. a) X hi b) Sc kho.
c) Cng ngh bo ch/ sn xut thuc. d) Ca ci vt cht.
3. a) Con ngi: s cp chuyn mn, c s vt cht v k thut: th s, nguyn vt liu hon ton
ph thuc vo Php.
b) c nhng tin cho cng nghip dc tuy rng sn xut vn th s trong iu kin chin
tranh.
c) c nn cng nghip dc bc u: XNDP 1, XNDP 2, v.v... mt s nc XHCN vin tr.
d) Ch o thng nht ton ngnh dc t Nam ti Bc, 1975-1986: thi k "bao cp" nhiu kh
khn v nguyn vt liu v c s sn xut,... T sau 1986: thi k "m ca" c chnh sch
Quc gia v thuc (1996), p dng GMP ASEAN (t 1996), GMP WHO (t 2005) c chin
lc pht trin n 2010 v 2020.
Bi 2
1. Nh s trong gio trnh
2. a) Cng thc b) Bo ch thuc nguyn mu
3. b) Dng bo ch thch hp d) Nhng nguyn liu bao b ng gi
f) Kim tra, kim sot h) Bo qun
4. a) Tnh cht vt l b) Tnh cht ho hc
c) S phn ca thuc trong c th
5. a) Tnh ho tan trong nc b) Kh nng ho tan trong nc
6. a) m b) nh sng
7. a) Phn hu b) Tng k
8. a) Nghin cu Dc ng hc b) C ch c) Tr liu
9. a) Vo c th b) Sinh kh dng
10. b) ng a thuc vo c th d) T dc v cht ph gia
f) Quy trnh sn xut
Bi 3
1.d 2.d 3.d 4.d 5.d 6.a 7.d
8.d 9.d 10.d 11.d 12.c 13.d 14.a
GLP v GSP
1.d 2.d 3.d 4.S 5.S 6.S 7.S 8.S
9. 10. 11.S 12.S 13. 14.S 15.S 16.d
17.c 18.d 19.d 20.c 21.c 22.C 23.C
Bi 4
1.d 2.d 3.d 4.c 5.d
Bi 5
1.a 2.d 3.c 4.a 5.b
6.c 7.d 8.c 9.d
Bi 6
1.c 2.d 3.c 4.d 5.e 6.d 7.d
8.a 9.c 10.d 11.a 12.d 13.e
Bi 7
1.a 2.d 3.c 4.c 5.b 6.c 7.c 8.b
9.d 10.d 11.b 12.b 13.c 14.a 15.c 16.d
17.d 18.c 19.d 20.b 21.b 22.c 23.d 24.d
25.d 26.d 27.d 28.a 29.b 30.d 31.b
Bi 8
1.d 2.a 3.c 4.d 5.c 6.c 7.d
8.d 9.a 10.a 11.c 12.b 13.d 14.d
15.b 16.c 17.e 18.b 19.c 20.b 21.a
22.c 23.b 24.d 25.c 26.c 27.d
Bi 9
1.b 2.d 3.a 4.c 5.c 6.d 7.d
8.d 9.c 10.b 11.d 12.c 13.c 14.a
15.a 16.a 17.c 18.d 19.d 20.c 21.d
22.d 23.c 24.d 25.c 26.b 27.c 28.c
Bi 10
1.e 2.b 3.a 4.c 5.d 6.b 7.c 8.a
9.d 10.c 11.b 12.d 13.c 14.c 15.c
Bi 11
1.e 2.d 3.c 4.c 5.d 6.d 7.c
8.b 9.c 10.b 11.b 12.b 13.b 14.c
15.c 16.c 17.d 18.b 19.c 20.b
Bi 12
1.c 2.d 3.d 4.d 5.a
6.b 7.d 8.a 9.e

Chu trch nhim xut bn :
Ch tch HQT kim Tng Gim c NG TRN I
Ph Tng Gim c kim Tng bin tp NGUYN QU THAO
Chu trch nhim ni dung:
Ch tch HQT kim Gim c CTCP Sch HDN
TRN NHT TN
Bin tp v sa bn in :
PHM TH PHNG
Trnh by ba :
BI QUANG TUN
Ch bn :
INH XUN DNG

CNG NGH BO CH DC PHM
M s : 7K727M7DAI
In 1.000 bn, (Q: 96) kh 19 x 27cm ti Cng ty CP In Anh Vit
a ch: S 74, ng 310 ng Nghi Tm, Ty H, H Ni
Giy php KKH xut bn s: 874 2007/CXB/7 1918/GD
In xong v np lu chiu thng 1 nm 2008.


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B Y T

l nhit bay hi ca nc vo khng kh, nu t

), nn gradien nhit trong vt liu

, nhng cn ch l chn nhit sy th no nhit bu t t

(bit NaCl = 58,5)?

trong 1 lt dung dch 2% MgCl

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