Chuyn 4:

K thut bo ch dung dch thuc v

phng php kim nghim
Phn I. M u
T thi nguyn thu con ngi bit dng cy c v
khong vt quanh mnh cha bnh. T ch ban u dng
nguyn liu lm thuc trng thi t nhin, dn dn ngi ta
bit ch bin bo ch chng thnh cc dng thuc n gin
tin dng v d tr dng hng ngy. Cng vi s pht
trin ca khoa hc vic bo ch thuc ngy cng c nghin
cu v pht trin hon thin, trong bo ch thuc dng
dung dch em li hiu qu ln trong vic phng v tr
bnh. Chnh v vy nhm chng ti tm hiu chuyn :
K thut bo ch dung dch thuc v phng php kim
nghim

Phn II. Ni dung

I. i cng v dung dch thuc.
1. nh ngha, c im v phn loi dung dch
thuc:
Dung dch thuc l nhng ch phm lng c iu ch
bng cch ha tan mt hoc nhiu dc cht trong mt dung
mi hoc mt hn hp dung mi. Dung dch thuc c th dng
trong hoc dng ngoi.
Cc dng bo ch xt v mt cu trc ha l c coi l
cc h phn tn. Mt h phn tn bao gm cht phn tn v
mi trng phn tn, khc vi pha phn tn b phn chia gin
on, mi trng phn tn mang tnh cht lin tc. H phn
tn c chia lm 3 loi theo kch thc ca cc tiu phn tn
nh sau:

- H ng th (h phn tn phn t): Bao gm cc dng

thuc c dc cht phn tn di dng phn t hoc ion (dung
dch thuc ung, thuc tim...).
- H di th: Dng thuc bao gm 2 pha khng ng tan:
pha phn tn v mi trng phn tn, trong kch thc tiu
phn phn tn t hng trm nanomet n hng trm
micromet.
- H siu vi d th (hay h phn tn keo): Kch thc tiu
phn phn tn t 1 - 100 nm

th sau y minh ha cch phn loi trn:

Hnh 1. th biu din s ph thuc ca din tch b

mt ring (S) trong h phn tn theo kch thc tiu phn
phn tn (a).
* Phn loi dung dch:
- Phn loi theo cu trc ha l: Dung dch thuc bao gm
dung dch tht, dung dch keo, dung dch cao phn t.

- Phn loi theo trng thi tp hp: Dung dch cht rn

trong cht lng, dung dch cht lng trong cht lng, dung
dch cht kh trong cht lng.
- Phn loi theo bn cht dung mi: Dung dch nc, dung
dch du, dung dch cn.
- Phn loi theo xut x cng thc pha ch: Cc dung
dch pha ch theo cc cng thc quy nh trong Dc in gi
l cc dung dch dc dng. Cc dung dch pha ch n ca
bc s gi l dung dch pha ch theo n.
2. u nhc im ca dung dch.
a. u im:
Dung dch thuc l dng thuc c dng nhiu nht trong
iu tr, so vi cc dng thuc khc do c nhiu u im, khi
c s dng di dng dung dch, dc cht c hp thu nhanh
hn cc dng thuc rn v trong cc dng thuc rn, dc cht
phi tri qua giai on ha tan trong dch ca c th. Mt s
dc cht di dng dung dch khi tip xc vi nim mc khng
gy kch ng nh khi dng di dng th (natri bromid, natri
iodid, cloral hydrat,...).
b. Nhc im:
Tuy vy, trong dung dch thuc, dc cht thng c n
nh km, cc phn ng thu ngn, oxy ha, racemic ha,
phn ng to phc cng nh s pht trin ca vi khun, nm
mc c th l nguyn nhn phn hy dc cht.
3. Thnh phn ca dung dch thuc
Dung dch c hai hp phn thng c gi l dung mi v
cht tan, cht tan trong dung dch thuc bao gm dc cht v
cc cht ph vi cc vai tr nh sau:
- Cht ph n nh (chng oxy ha, thy ngn...)
- Cht lm tng tan.
- Cht bo qun (chng vi khun, nm mc)

- Cht to h m pH, iu chnh pH (m bo n

nh, sinh kh dng ca thuc, trnh kch ng...)
- Cc cht ng trng (thng dng trong dung dch thuc
tim, thuc nh mt).
Cc dung mi c la chn cho dung dch thuc ty theo
mc ch, tc dng iu tr v ng dng thuc...
Dc cht v dung mi c dng pha ch dung dch
thuc phi t cc ch tiu ra theo tiu chun Dc in
v l ha tnh, tinh khit, gii hn tp cht... Dung mi
phi khng c c tc dng dc l, khng c hi, khng tng
k vi dc cht v bao gi.
4. Phn loi cht tan v dung mi theo phn
cc, kh nng ha tan ca dung mi.
phn cc ca dung mi v cht tan ph thuc vo kiu
lin kt ca cc nguyn t v s sp xp ca cc nhm
nguyn t trong phn t.
Lin kt in ha tr hay lin kt d cc (lin kt ion lng cc) to nn phn t phn cc.
Lin kt cng ha tr (lin kt c s gp chung in t)
to nn phn t khng phn cc.
S c mt cc nhm phn cc nh OH, - NH2, - SH, CHO, - COOH, = CO trong phn t lm cho cc cht tr nn
phn cc.
Loi cht c phn cc trung gian gia hai loi phn
cc v khng phn cc gi l cht bn phn cc.
Qu trnh ha tan xy ra khi lc ht gia cc phn t
dung mi vi phn t hoc ion cht tan ln hn lc ht gia
cc phn t ion cng loi.
Lc ht hay tng tc tnh in gia dung mi v cht
tan c th bao gm cc loi:
- Lc ht ion lng cc (Na+Cl vi H2O)
- Lc ht lng cc lng cc (nitribenzen nc)

- Lc ht lng cc kh lng cc (methanol benzen)

- Lc ht kh lng cc kh lng cc (parafin hexan).
Cc lc tng tc trn thc y qu trnh ha tan xy ra
nhanh.
Nguyn t c bn xt on kh nng ha tan l cc
cht c tnh cht tng t th ha tan trong nhau.
Nh vy cc cht phn cc tan trong dung mi phn cc,
khng tan trong dung mi khng phn cc, v ngc li vi cht
khng phn cc ch tan trong dung mi khng phn cc.
Hng s in mi biu th mc phn cc ca mi
dung mi. Dung mi phn cc mnh c hng s in mi ln,
dung mi cng km phn cc c hng s in mi cng nh.
Bng 2. Hng s in mi v kh nng ha tan ca
mt s dung mi
Hng s in
mi (tr s
gn ng)

Dung mi

Kh nng ha tan

Nc

Mui v c, hu
c

50

Cc glycol

ng, tanin

30

Ethanol, methanol

Du thu du

20

Cc aldehyd, xeton, cc Nha, tinh du, cc

alcol bc cao, ether, alcaloid,
cc
este..
phenol...

Benzen,
tetraclorid Cht bo, parafin,
carbon, ether du ha, cc hydrocarbon...
du khong vt, du
thc vt.

80

Vic phi hp cc dung mi lm thay i hng s in

mi v phn cc ca hn hp dung mi, t lm thay

i kh nng ha tan i vi mt cht tan, ln hn nhiu so

vi vic dng tng dung mi.
Lin kt hydro l lin kt gia 2 nguyn t nh mt
nguyn t hydro lm trung gian. S hnh thnh lin kt Hydro
gia cc cht vi nc lm tng lm ha tan ca cc cht
trong nc nh i vi cc cht c ha chc alco, amin, amid.
5. ha ca cht tan v nng dung dch.
tan ca mt cht trong mt dung mi mt iu kin
nhit , p sut xc nh l t l gia lng cht tan v lng
dung mi ca dung dch bo ha cht tan trong dung mi
cho khi qu trnh t n trng thi bo ha.
II. Cc loi dung mi:
1. Dung mi nc:
Nc nguyn cht l mt loi dung mi lng tnh. Nc mun
dng lm dung mi th nc phi kh khong. kim tra cht
lng kh khong u ng ra ca nc kh khong c np
mt ng h o in tr. Nc kh khong tt c in tr
trn 1,4 triu /cm , nu nh hn 1 triu /cm l nc c cht lng km.
kh khong nc ngi ta thng dng phng php trao
i ion v khng cn ngun nhit, d thc hin trong cc
hiu thuc v phng bo ch. Ngoi ra cn c th dng phng
php in thm phn nhng chng t c dng.
2. Cc dung mi phn cc thn nc.
Cc alco ni chung l nhng dung mi phn cc do s c
mt ca cc nhm hydroxyl trong phn t ca chng. Alcol
bc nht l nhng cht tan trong nc v l dung mi tt cho
cc cht phn cc mnh.
Mch hydrocarbon trong dy ng ng cng tng, tnh
phn cc v kh nng trn ln vi nc ca alcol cng gim. Cc
alcol bc cao c nhiu nhm hydroxyl c tnh phn cc mnh
hn cc alcol tng ng ch c mt nhm hydroxyl.
* Ethanol:

Trong cc alcol, ethanol c s dng rng ri nht trong

ngnh dc. N c th ha tan cc acid, cc kim hu c, cc
ancaloid v mui ca chng, 1 s glycosid nha, tinh du, mt
s lipid mu, ... ethanol khng ha tan pectan, protid, enzym...
Ethanol to hn hp vi bt c t l no vi nc v glycerin.
Khi trn ln ethanol vi nc s c hin tng ta nhit v th
tch hn hp thu c nh hn tng th th tch ca ethanol
v nc tham gia vo hn hp.
i vi mt s dc cht, hn hp ethanol nc c kh nng
ha tan cao hn so vi cc thnh phn ethanol v nc ring r.
Ethanol c u im l c tc dng st khun. Mt s dc
cht vng bn trong ethanol hn l trong nc. Ethanol l dung
mi c kh nng lm tng n nh v sinh kh dng
thuc ung. Tuy nhin ethanol cng c nhc im l khng
hon ton tro v mt dc l, d bay hi, d chy, lm ng
vn albumin, cc enzym v d b oxy ha.
* Glyxerin:
L mt sn phn thu c khi x phng ha cht bo,
glyxerin l mt cht lng khng mu, snh, v ngt, nng, c
phn ng trung tnh.
Glycerin trn ln vi ethanol v nc bt c t l no,
khng trn ln vi cloroform, ether, du m.
Glycerin ha tan mt s mui cc acid hu c v v c,
ha tan ancaloid v mui ca chng, cc tanin, ng...
Glycerin khan nc rt d ht m v thng gy kch ng
da, nim mc. V vy trong bo ch ch dng glycerin dc
dng c t trng 1,225 1,235 cha 3% nc, khng gy kch
ng. nng 25%, glycerin c tc dng st khun. Glycerin
ch yu thng c dng trong cc dng thuc dng ngoi.
3. Cc dung mi khng phn cc thn du.
Du thc vt: L hn hp cc glycerit ca cc acid bo bc
cao. Thng dng du lc, du hng dng. Cc du thc vt
khng tan trong nc, th d ha tan trong cn, d ha tan

trong cloroform, ether v ether du ha. Du thc vt ha tan

c mt s dc cht hu c nh salon, long no, mentol, tinh
du, cc alcaloid base, mt s vitamin nh A, D.
Cloroform: Trn ln c vi a s cc dung mi hu c. L
dung mi tt cho cht bo, du m, tinh du, cc ancaloid
base,... dung mi ny t c dng trong dung dch thuc.
III. K thut chung iu ch dung dch thuc.
K thut iu ch dung dch thuc ph thuc vo tnh
cht l ha ca cc thnh phn v cc mc ch iu tr
thuc.
Nhn chung, k thut iu ch bao gm cc giai on
chnh sau y:
1. Cn hoc ong dc cht v dung mi.
2. Ha tan.
3. Lc
4. Hon chnh ng gi thnh phm.
1. Cn, ong dc cht v dung mi.
Cn ong chnh xc m bo hm lng thuc theo
quy nh ca dc in. Trong phng bo ch khi pha ch c
dung dch c nng % khi lng trn th tch, thng dng
h thng buret. Phng php ny s dng cc dung dch m
c pha sn lm tng hiu sut v gim sai s cn ong
rt thun tin cho vic pha ch theo n.
2. Ha tan v cc yu t nh hng.
2.1. Qu trnh ha tan:
Qu trnh ha tan xy ra theo nguyn l nhit ng hc
trong iu kin khi nng lng t do ( G) nh hn khng. Phng trnh nhit ng hc c p dng l:
G = H - TS

Trong H l nhit to ra hay thu vo khi qu trnh xy

ra (nhit ha tan), S l entropy - biu th mc khng trt
t ca h. T l nhit nhit ng hc.

Nhit ha tan ( H) c mi quan h vi nhit solvate ha (

Hsolv) v nng lng ph v cu trc tinh th ca cht rn (E)
theo phng trnh sau y:
H = E + HHsolv

Trong E lun lun dng (E>0) v HHsolv <0

Trong hu ht cc trng hp E > HHsolv, do vy qu
trnh ha tan khi H>0 l qu trnh thu nhit. Trong mt s
trng hp HHsolv > E, do H<0, qu trnh xy ra khi
to nhit. Nguyn l nhit ng hc nu trn l c s xt
on nh hng ca nhit n tan cng nh tc
ha tan.
2.2. Cc yu t nh hng n tan v tc ha
tan dc cht:
2.2.1. tan ca cht kh trong cht lng:
Theo nh lut Henry tan ca cht kh t l thun vi
p sut kh trn b mt dung dch, biu th bng phng
trnh sau:
w = kp
Trong w l cht kh ha tan trong 1 n v th tch
cht lng, k l hng s t l. tan ca cht kh trong dung
dch s gim khi tng nhit . Vn dng trong ngnh Dc,
nhiu chuyn lun dc in yu cu s dng nc ct va
mi un si loi phn ln lng kh ha tan trong n ct nh
CO2, O2... nhm mc ch trnh nh hng ca cc cht kh
ny n n nh ca dc cht trong dung dch thuc.
2.2.2. tan ca cht rn trong cht lng:
Cc yu t nh hng n tan ca cc dc cht rn
trong dung dch c ngha quan trng trong pha ch thuc,
ln lt c kho st nh sau:
* nh hng ca nhit :
Vi qu trnh ha tan dc cht c s thu nhit ( H > 0)
theo nguyn tc Le Chatelier, vic tng nhit s thc y
qu trnh ha tan, lm tng tan ca dc cht. Ngc li khi d10

c cht ha tan ta nhit ( H<0) vic tng nhit s lm

gim tan ca dc cht.
Tuy nhin i vi phn t kt tinh ngm nc trong qu
trnh ha tan, nhit c th nh hng n ho tan
theo chiu hng ngc nhau do c s mt nc kt tinh chuyn
sang
dng
khan.

* nh hng ca bn cht v c im cu trc phn t

ca cht tan v dung mi:
Bn cht v c im cu trc ha hc ca cht tan v
dung mi l nhng yu t ha hc ni ti nh hng n

11

tan. Cu trc phn t cng nh cc nhm choc c trong phn

t cht tan v dung mi quyt nh c tnh phn cc. V
d in hnh nh phenol khi c th nhm OH tng tan
trong nc gp 100 ln so vi benzene. Cc nhm choc thn nc
OH, NH, SH... c trong phn t cht tan s lm tng tan
ca cht ny trong nc do tng phn cc.
Vic chuyn mt s dc cht dng acid yu sang dng
mui s lm tng tan do cc mui ny c phn ly ln
hn. Trong mt s trng hp cn lm gim tan bng cch
chuyn dc cht sang dng este ha nhm hn ch s phn
hy, v ng nh cloramohenicol chuyn sang dng
cloramphenicol, palmitat, erythromycin chuyn sang dng
erythromycin propionate.
* nh hng ca c tnh kt tinh, hin tng a hnh v
s solvate ha n tan:
Mt dc cht c th kt tinh di nhiu dng tinh th khc
nhau ty theo iu kin kt tinh. Cc dng kt tinh khc nhau
s c cu trc tinh th bn vng mc khc nhau t
c tan khc nhau. V d Ampicillin khan c tan ln hn
ampicillin trihydrat.
Dng kt tinh c cu trc tinh th bn vng nn thng
kh tan hn dng v nh hnh. Novobiocin c dng v nh
hnh d tan hn dng kt tinh 10 ln.
* nh hng ca kch thc tiu phn dc cht n tan:
tan ca dc cht tng ln khi kch thc tiu phn gim
i do nng lng t do trn b mt tip xc tng ln, biu th
trong phng trnh sau y:
log

S
2 EM

S0 2,303RT r

Trong S l tan ca tiu phn c nghin mn c

ng knh r, S0 l tan ca dc cht c kch thc tiu phn
ban u, E l nng lng t do trn b mt tip xc, M l trng
lng phn t, p l t trng cht rn, R l hng s kh, T l

12

nhit ng hc. Nh vy vic nghin mn dc cht rn s

lm tng tan mt mc no .
* nh hng ca pH dung dch n tan:
i vi cht in li yu, nh hng ca pH dung dch n
tan c xem xt trong 3 trng hp khc bit: Cht tan l
cc acid yu, base yu v lng tnh
- Vi acid yu: (Nh cc barbituric, phenylbutazon,
nitrofuratoin...) mi quan h gia tan S vi pH v pKa biu
th bng phng trnh:
log

S S0
pH pKa
S0

(SO l tan ca dc cht dng khng phn ly)

- Vi cc base yu: (Nh alkaloid, clopromazin...) c phng
trnh tng t vi biu thc phn s o ngc khi thay pKb
bng pKa.
log

S0
pH pKa
S S0

Nh vy, khi pH ca dung dch tng (kim ha dung mi) s

lm tng tan ca acid yu v gim tan ca cc base
yu, trng hp ngc li khi gim pH dung dch (acid ha dung
mi).
- Vi mt s cht lng tnh (Nh cc acid amin, cc
sulphonamid, oxytetracylin...) cc cht ny c t nht 2 hng
s in ly.

HAH

K a1
H

HA

(Cation)

Ka 2

(phn t trung ha

(Amion)
im ng in)

13

 pH nh hn im ng in, c phng trnh biu

th mi quan h: tan, pKa, v pH
log

S0
pH PKa1
S S0

pH ln hn im ng in, c phng trnh biu

th mi quan h tan, pKa v pH s l:
log

S S0
pH PKa2
S0

Nh vy tng pH di im ng in s lm gim
tan ca cht tan lng tnh v trn im ng in s lm
tng tan.

* nh hng ca cc ion cng tn:

14

Trong dung dch cc ion cng tn A+ hoc B- vi cc ion

ca cht tan tham gia vo cn bng phn li ca cht tan AB.

AB (rn)

AB (dung dch)

A+ + B-

Khi c mt cc ion cng tn, nng cc ion bn phi

ca phng trnh tng ln, y qu trnh ha tan i theo
chiu nghch lp li cn bng phn ly, do lm gim
tan.
* nh hng ca cc cht in ly:
S c mt ca cht in ly lm gim hot ion, lm
gim phn li ca cc cht tan t lm gim ha tan
ca cc cht.
Nh vy ha thnh nhanh cn ha tan theo th t cc
cht km tan c ha trc. i vi cc cht in gii cn pha
long nng khi phi hp vi dung dch cc cht km tan
trnh nh hng ca cc ion c th lm kt ta ca cc cht
ny.
nh hng ca cc cht to phc hoc dn cht v cc cht
in hot n tan c xem xt trong phn cc phng
php ha tan c bit.
2.2.3. Tc ha tan:
Tc ha tan ca dc cht c biu th theo phng
trnh Noyes Vithney:
dC
K . A(Cs Ct )
dt

Trong :
K: hng s tc ha tan
A: l din tch b mt tip xc ca dc cht vi dung mi
Cs: l nng bo ha ca dc cht
Ct: l nng dc cht ti thi im t

15

Nu thay

D
h

th tc ha tan c biu th theo ph-

ng trnh:
dC
D. A

(Cs Ct )
dt
h

Trong : D l h s khuch tn ca dc cht trong dung

mi
h l b dy lp khuch tn.
Cc yu t nh hng ti tc ha tan c th c xem
xt trnh tc ng ca chng n cc i lng trong phng
trnh biu th tc ha tan.
* nh hng ca nhit n tc tan: Tr mt s t
trng hp cht c qu trnh ha tan ta nhit vic tng nhit
s lm gim tan t gim tc ha tan, phn ln
cc cht c tan v tc tan tng khi tng nhit do
h s khuch tn ca cht tan trong dung mi tng cao,
nht ca dung mi gim.
V d: Cafein t tan trong nc nhit thng nhng d
tan nhit cao. i vi cc dung mi c nht cao
(glyxerin, propylene glycol...) ha tan nhanh cn un
nng nh khi ha tan iu ch cc dung dch natri bonat trong
glycerin, cloramphenicol 5% trong propylene glycol, natri
benzoate trong siro n...
Bng 2.3. H s khuch tn ca mt s dc cht
H s khuch tn

Dc cht

200C

700C

Kali clorid

1,71

4,98

Natri clorid

1,34

3,88

Kali sufat

1,05

3,04

16

Natri sufat

0,89

2,58

Magie sufat

0,46

1,32

Acid citric

0,57

1,65

Acid tarric

0,62

1,81

Saccarose

0,37

1,07

Albumin

0,0088

0,0255

Vic nghin nh dc cht lm tng tc ho tan do lm

tng din tch b mt tip xc ca cht tan vi dung mi.
Vic khuy trn trong qu trnh ho tan: lm tng tc
ho tan do cu trc cc lp b ph v khi a lp dung mi mi
vo gn b mt cht tan ni c lp dung dch bo ho
lm tng s chnh lch nng , b dy lp khuch tn tr
nn v cng nh. Kt qu tc ng vo 2 i lng ny lm tng
nhanh tc ha tan.
Cn lu khi ho tan cc tiu phn cht keo: cn yn
cho cc cht keo ht nc trng n hon ton, trnh khuy trn
lm keo dnh cc tiu phn, lm gim din tch tip xc ca
cht tan vi dung mi. Trong trng hp ny cn p dng phng
php ho tan t trn xung (perdescensum) hay cn gi l phng php ho tan quay vng.
Dc cht tn nh c rc ln mt thong ca dung mi
hoc cho vo mt ti vi treo tip xc vi b mt dung mi.
Do tip xc vi lp dung mi b mt, dc cht s tan v tr
thnh mt dung dch bo ho. Lp dung dch bo ho ny c t
trng ln nn chuyn ng xung y bnh y lp dung
mi mi c t trng nh ln b mt, tip tc ho tan mt lng
cht tan mi. Phng php ny thng c s dng ho tan
cc cht bc keo (acgiron)... hoc iu ch sir ng n.
2.3. Cc phng php ho tan c bit:
Danh t ho tan (Solubinisation) c dng ch qu
trnh phn tn cc phn t ca cht kh tan hoc t tan

17

trong mt dung mi, nh s trung gian ca nhng cht gi l

cht lm tan (Solubinisant). ho tan cc cht kh tan, c
th dng cc phng php c bit nh to dn cht d tan,
dng hn hp cc dung mi, dng cc cht trung gian thn nc,
dng cht in hot.
2.3.1. Phng php to dn cht d tan
i vi mt s cht kh tan trong dung mi c th s dng
cht c kh nng to thnh dn cht d tan vi dc cht. Dn
cht ny cn gi c tc dng dc l ca dc cht ban u,
cht tr tan c trong dung dch phi khng em li nhng tc
dng bt li cho dung dch dc cht. in hnh loi ny l dung
dch lugol, trong c vai tr to vi I 2, thnh dn cht KI3 rt
d tan trong nc.
I2 + KI -> KI3
Tc ha tan c quyt nh bi tc phn ng to
dn cht KI3. Nng KI cng m c tc phn ng
cng nhanh. Do , d dng ha tan I 2 ch cn lng nc
ti thiu to dung dch Ki bo ha (ng thi cht tan). Khi I 2
chuyn thnh f KI3 v ha tan ht mi thm nc pha long ti
th tch.
Tng t, ha tan thu ngn II iodide trong nc, KI kt
hp vi HgI2 to phc Kali tetraiodomerrcuriat.
HgI2 + KI -> K2 [HgI4]
2.3.2. Phng php ha tan dng hn hp dung mi:
Phng php ha tan ny bao gm vic s dng mt hn
hp nc, nhng dung mi thn nc khc (ethanol, glyxerin,
prylen glycol,...) lm cho hn hp dung mi c phn cc
gn vi phn cc ca dc cht kh tan trong nc t ha
tan dc cht d dng.
Cc dung mi thng dng l:
- Cc monoalcol nh ethanol, isopropanol, alcol benzylic...
- Cc polyalcol nh glyxerin, proppylen glycol, butylen
glycol, polyetylen glycol...

18

- Cc dn cht amin nh etylendiamin, dietyl aminethanol...

Trong thc hnh bo ch, ngi ta thng dng cc hn hp nc - alcol ha tan camfor, hn hp glycerin - alcol - nc
ha tan mt s ancaloid, glycoside. V d: Dung dch digitatin
0,1% c thnh phn dung mi ethanol - glycerin - nc. Cng
thc thuc in hnh s dng hn hp dung mi l dung dch
bromoform c thnh phn bromoform - glyxerin - ethanol, t
l 1:3:6.
Mt s dung dch s dng hn hp dung mi, ngoi vai tr
lm tng tan cn tng n nh v sinh kh dng ca
thuc c ghi trong dc in Anh nh:
- Dung dch phenolbarbital 0,3% (hn hp dung mi
ethanol - glyxerin - nc).
- Dung dch paracetanol 2,4% (hn hp dung mi ethanol,
propylene, glycol - nc.

2.3.3. Phng php ha tan dng cc cht trung gian

thn nc:
C th s dng mt s cht hu c thn nc ha tan
mt s cht kh tan. Nhng cht trung gian ha tan ny thng
l nhng cht thn nc. Phn t ca chng mang nhiu
nhm - COOH, - OH, nhm amin, nhm sulfat..., phn cn li l
nhng gc hydrocarbon mch thng hoc mch vng. Trong
thc hnh bo ch thng dng cc acid hu c nh acid lactic,
acid tatric, natri salicylat, sorbitalm glucose, manitol...
Vai tr trung gian ha tan ca cc cht ny l do mt mt
chng c phn hu c c i lc vi phn s nc ca cht kh
tan, mt khc chng c nhng nhm chc thn nc c i lc
i vi phn t nc.
Tng tc tnh in ca cc phn t lng cc cht trung
gian ha tan vi c hai loi phn t cht tan v dung mi li

19

ko phn t cc cht t tan vo dung mi nhiu hn lm

tng tan.
Trong bo ch t lu, ngi ta bit n dng natri
benzoat ha tan cafein, anestezin, antifebrin, pyramidon,
dng acid citric ha tan calci glycerol phosphate dng
antipyrin hoc uretan tng tan ca quinine... Dng acid
lactic ha tan haloperidol hydroclorid. Ngi ta cng nhn
they hin tng trung gian ha tan trong thin nhin.
Bng phng php ny c th thu c kt qu ha tan tt
nhng i khi cn phi s dng cc cht trung gian ha tan vi
t l ln, c khi ln hn c lng cht cn ha tan.
2.3.4. Phng php ha tan dng cc cht din hot
(cht hot ng b mt):
Trong k thut bo ch hin i, ngi ta cn hay dng cc
cht in hot lm cht trung gian ha tan. Cht in hot l
nhng cht khi tan trong dung mi, c kh nng lm gim sc
cng b mt ca dung mi. c im cu to ca cc cht
in hot l phn t ca chng gm 2 phn: phn thn nc
v phn thn du. nng thp cc cht in hot c th
phn tn di dng phn t trong nc to thnh cc dung
dch tht. Nu nng tng ln n mt gii hn no , cc
phn t cht in hot tp hp thnh micelle v dung dch
tr thnh dung dch keo. Nng ny c gi l nng
micelle ti hn. Trong micelle, cc phn t cht in hot c
th c sp xp thnh hnh cu, thnh cc lp song song
hoc thnh hnh tr. Cc phn t hoc tiu phn cht tan
c phn tn, hp th vo trong cu trc ca cc micelle
hoc vo gia cc lp micelle, cc phn t cht tan c gi li
trong micell hoc vo gia cc lp micelle, cc phn t cht
tan c gi li trong micelle khng tham gia vo cn bng
bng ca dung dch trng thi bo ha, do nng cht
tan trong ton b dung dch tng ln. thm nhp ca cc
tiu phn dc cht vo trong micelle cht in hot ph
thuc vo tnh phn cc ca cc phn t dc cht.

20

Nh vy, iu kin cht in hot c tc dng lm

tng tan ca mt cht khc l cn c dng vi lng ln,
to c nng ln hn nng micelle ti hn. C ch lm
tng tan ca cht in hot l hp th cht tan vo
micelle. Dung dch thu c ngoi cu trc l dung dch tht
cn l dung dch keo.
Trong thc hnh bo ch cc Tween l nhng cht in
hot hay c dng lm cht trung gian ha tan. Dung dch
Tween 20 (5%) trong nc c th lm tan mt s cht kh tan
hoc khng tan trong nc. Tween c th ha tan trong nc cc
cht st khun dn cht ca phenol, cc hormol steroid cc
vitamin tan trong du, cc khng sinh (cloramphenicol,
griserofulvin...), cc sulfamit, cc barbituric... Tween cn c
dng ha tan tinh du trong nc iu ch nc thm. Vi
mt lng Tween gp 5 ln lng tinh du c th iu ch mt
dung dch tinh du 1 - 2% trong nc, trong sut v n nh
lu di. iu cn ch l trong cc dung dch thuc ung,
khng nn dng qu 3% Tween v gy cho ch phm mi v
kh chu. Mt khc, cht in hot cng c th lm gim
hiu lc ca mt s dc cht (khng sinh v cht st khun).
3. Lc dung dch:
Lc l qu trnh loi tiu phn cht rn khng tan trong
dung dch bng cch cho dung dch i qua vt liu lc
thu c dung dch trong.
Lc l phng php thng dng nht lm trong dung
dch sau khi ha tan dc cht trong dung mi.
3.1. Qu trnh lc:
Qu trnh lc xy ra c l do kh nng ca cc vt liu
lc, thng l nhng mng chn c l nh, cho php cht lng
i qua v gi li cc tiu phn cht rn.
Ngi ta thng so snh qu trnh lc vi mt qu trnh c
hc khc l qu trnh ry. Nhng tiu phn c kch thc ln
hn kch thc l xp ca vt liu lc b gi li trn mng lc.
Tuy nhin, nhiu trng hp tm vt lieu lc c kh nng gi li
c nhng tiu phn c kch thc nh hn kch thc l xp ca
21

mng lc Trong nhng trng hp ny qu trnh lc khng cn

l mt qu trnh c hc n gin na m phi c gii
thch bng mt s hin tng phc tp nh hin tng hp ph,
hin tng mao dn. Vic gi li trn mng lc nhng tiu
phn b hn kch thc l xp cn nh cc l xp c hnh
dng khc khuu. Mt khc cc tiu phn cht rn t tp
trn tm vt liu lc cng ng vai tr mt mng lc th hai.
Tc lc, ph thuc vo nhiu yu t.
C th biu din tc lc ca mt cht lng qua mng
lc theo phng trnh Hagen Poiseuille.

Sr 4 ( P p )
V
8 l
Trong :

r: Bn knh trung bnh l xp mng lc.

P - p: Hiu s p lc tc dng ln hai pha ca

mng lc.
S: Din tch b mt lc.
: nht ca cht lng cn lc.

L: Chiu di l xp.
Phng trnh cho thy tc lc t l thun vi din tch
b mt lc, vi lu tha bc 4 ca bn knh l xp, vi hiu s
p sut tc dng ln 2 mt mng lc, t l nghch vi chiu
di ca cc mao qun trong mng lc v nht ca dung
dch cn lc.
3.2. Cc vt liu lc, dng c lc v phng php lc:
C th dng vt liu lc khc nhau tu theo kch thc ca
cc tiu phn cht rn trong dung dch, tu theo tch cht
v lng dung dch cn lc v tu theo trong mong mun
c.
qu trnh lc c nhanh chng v thu c dch lc
trong, khi la chn vt liu lc, cn ch cc iu kin sau
y:

22

- Vt liu lc phi c nhng l lc c kch thc nht nh

v ng nht.
- Phi bn vng v mt c hc v ho hc i vi cht
em lc, (khng tham gia phn ng ho hc vi cc cht trong
dung dch, khng lm nhim bn dch lc....).
- Phi d ra v d phc hi kh nng lc.
- C th p dng cc phng php lc thch hp (lc nn,
lc chn khng...).
C th chia vt liu lc thnh cc loi nh sau:
- Vt liu i t si cellulose (giy, bng, vi).
- Vt liu l thu tinh xp: cc mng lc thy tinh xp.
- Vt liu lc l s xp: cc nn lc s xp.
- Vt liu lc ch to t cc cht polymer hu c tng hp
nhn to (nh cc este ca cellulose: cellulose acetate,
cellulose nitrat...).
3.2.1. Cc vt liu v dng c lc lm t si
cellulose:
Giy lc: giy dng lc l loi giy khng h cu to t
cellulose nguyn cht, p thnh mng. Giy lc trong bo ch
c chia lm 2 loi:
Loi xm: phm cht km v c cha silic Si2O3, Fe2O3, cc
mui clorid, carbonat trong qu trnh lc s chuyn 1 phn
sang dung dch, lm bn v lm bin cht dch lc. Khi dng
loi giy ny, phi ra k bng nc ct un si.
Loi trng: tt hn, khng cha cc tp cht nhng c nhc
didm l t thm nn lc chm hn loi xm.
Loi ny phn bit ra 3 loi khc nhau:
- Giy lc dy nhng c th tha (l lc ln) dng lc cc
dung dch snh nh siro, dung dch du...
- Trung bnh thng dng lc cc dung dch thuc. ng knh ca cc l lc trong khong 3 - 7 micromet.

23

- Giy lc khng tro c phm cht cao dng nh lng.

C ng knh l lc trong khong 1 - 1,5micromet.
Khi lc phi dng giy lc tt, ng nht, khng cha tp
cht ca g, mui st, cc clorid, kim loi kim, kim loi nng.
Giy lc cha kim loi nng c th lm bin i dung
dch thuc sau khi lc. Dung dch natri salysilat, cc dn cht
phenol, adrenalin s c mu h ng nu lc qua giy lc c vt
st. Giy lc cng c th hp ph cc cht tan trong dung
dch nh cc ancaloid, cc cht mu. Cc dung dch oxy ha
nh iod, kali permanganate... c th b kh trong qu trnh lc
qua giy lc.
Khi dng giy lc, bng lc, phi dng cc phu thy tinh
lm gi . Nu loi cn v ly dch lc, dng giy lc c
gp np v phu thy tinh c nghing ca thnh phu l
450. Nu mun ly cn, dng giy lc khng gp np v phu
thy tinh c thnh nghin 600. Hnh 2.11 gii thiu 1 s phu
lc thng gp trong thc hnh bo ch. Loi giy lc gp np
nh c nhiu np gp nn din tch b mt lc tng ln
nhiu, mt khc giy khng dnh cht vo thnh phu nn
tc chy nhanh hn.
Bng: trong thc hnh bo ch, thng dng bng lc
cc dung dch thuc dng ngoi da, thuc ung...
Bng dng lc phi t cc yu cu sau: khng c m,
c si di t 14 - 20mm, khng cha acid, kim, cht kh v
cc tp cht khc, c m ti a 9%, phi thm nc sau 10
giy.
Cc vt liu lc vi, len, d: C u im l bn v mt c
hc v ha hc. Nhc im ch yu l khng cho dch lc c
trong cao. Thng lc nhng khi lng ln cc cht lng
so snh nh cc siro thuc. Khi lc siro thng dng nhng ti d
(ti lc Hipocrate) hnh dng nh cc m chp, c th lng vo
khung thp hoc khung g. Pha trong ti, pha u nhn
ngi ta buc 1 si dy. Nh si dy ny c th lm chuyn
ng y ti lc v cht lng trong ti tng tc lc.

24

Tm lc Seizt (si cellulose kt hp amian) t trong

khung ca mng lc c kch thc l lc nh sau:
K hiu

ng knh l lc

Ek

1,4 - 1,8mcm

Eks

1,2 - 1,4 mcm

Eks1

1,0 - 1,2mcm

Eks2

0,3 - 1,0 mcm

ng lc KNIKFI: ng lc ny do Vin nghin cu ha dc

Kharcov ch to. Nguyn tc cu to ca ng lc nh m t
hnh 2.11, ng lc da trn s chnh lch p sut tnh, hiu
sut lc c th t 30lt/gi.
3.2.2. Cc vt liu lc lm t thy tinh xp, s xp.
Cc phu lc thy tinh xp c u im l tr v mt ha
hc v c l lc rt b thng dng lc dung dch thuc
tim v thuc nh mt. Phu lc thy tinh xp khng hp th
cc cht trong dung dch lc, do rt thch hp i vi cc
dung dch ancaloid, enzyme...
Kch thc l lc ca 1 s loi dng c lc vi cc vt liu
thu tinh xp, s xp nh sau:
- Phu lc thy tinh xp.
K hiu

ng knh l lc

G 00

500 - 200 mcm

G0

200 - 150 mcm

G1

150 - 90mcm

G2

90 - 45mcm

G3

45 - 15mcm

G4

15 - 5mcm

G5

1,5 - 1 mcm

- Nn lc s xp Chamberland.
25

K hiu

ng knh l lc

L1

8,9 - 4,7 mcm

L2

4,7 - 2,2 mcm

L3

2,2 - 2,0 mcm

L4

2 - 1 mcm

3.2.3. Cc mng lc polymer tng hp:

Mng lc c ch to t este ca cellulose, nh cellulose
acetate, cellulose nitrat c kch thc l lc t 0,05 mcm - 10
mcm, thng dng loi c l xp 0,45 mcm lc dung dch
thuc. Mng lc l xp 0,22 mcm thng c dng v khun
bng cch lc (loi b v khun). Mt s mng cn c ch to
t nguyn liu nylon, Teflon, polycinyclorid, polypropylene...
Cc mng lc polymer c mt lc cao (10 8 l/cm2) m
bo hiu sut lc cao.

Cc phng php lc:

Theo phng trnh Hagen - Poisseulille tc cht lng
i qua cc l ca vt liu ph thuc vo hiu s p sut tc
dng ln 2 mt ca mng lc. Ty theo s chnh lch p sut
gia 2 b mt ca mng lc, c th chia ra 3 phng php
lc:
- Lc di p sut thu tnh
- Lc di p sut gim (chn khng).
- Lc vi p sut cao (lc nn).
Trong trng hp lc di p sut thy tnh cht lng i qua
mng lc ti p lc t l thun vi chiu cao ct cht lng.
tng tc lc cc dung dch snh nht c th dng bin php
lc nng vi nhng phu c thnh i, gia 2 thnh phn
phu c nc nng hoc hi nc nng lu thng, hoc t nng
bng dng in. Trong phng php lc di p sut gim ngi
ta tng hiu s p lc gia 2 b mt ca mng lc bng cch

26

thc hin chn khng pha di ca mng lc nh cc loi

bm chnkhng hoc sc ht ca vi nc. Khi lc cc dung
dch nng trnh lm chn khng cao v c th lm si dung
dch. lc di p sut gim, ngi ta thng dng phu lc thu
tinh xp, s xp, lc Buchner.
Khi lc di chn khng, mt s p sut trn v di mng
lc ch c th t n tr s ti a 1 ctm. p lc ny trong 1
s trng hp (khi l ca tm vt liu lc ht sc nh) khng
to tc lc ln. Mun c tc lc ln hn, phi
dng phng php lc di p sut cao. Trong phng php ny
ngi ta dng p sut cao ca kh nn (c th n vi atm)
y dung dc qua mng lc. Thng thng ngi ta dng
khng kh nn. i vi cc cht d oxy ha nn dng kh nn
carbonic hoc nit.
Trong cng nghip bo ch, ngi ta thng dng phng
php lc nn, mng lc c t trong khung thp khng g
lc khi lng ln dung dch.
4. Hon chnh ng gi v kim nghim thnh phm:
Dung dch thuc trc khi ng gi thnh phm c kim
tra cht lng. Dung dch thuc phi t tiu chun cht lng
ra v cc mt ch tiu l ha nh trong, t trng,
nh tnh, nh lng cc thnh phn dc cht, dung mi...
Cc dung dch thuc thng c ng l thy tinh hoc l
cht do (polyetylen, polyvinyl clorid, polystyrene). L thy
tinh, cht do cn t yu cu cht lng theo dc in nh v
trnh trung tnh, khng tng k vi dc cht, dung mi...
Cc np nt cao su khng c hp th dc cht cng nh
a tp cht (c trong thnh phn cao su) vo dung dch
thuc.
5. Pha ch dung dch thuc theo n.
Theo ngun gc cng thc thuc c chia lm 2 loi:
- Thuc sn xut theo l m vi s lng ln theo quy trnh
sn xut v tiu chun cht lng c ng k vi cc qun
l c.

27

- Thuc bo ch theo n ca bc s
Thuc sn xut theo l c u im l cung ng c s lng
ln thuc cho ngi bnh, cht lng ca thuc c kim sot
cht ch theo l sn xut, nhng c nhc im l khng th
hon ton ph hp cho vic iu tr bnh nhn c th trng
khc nhau.
Thuc bo ch theo n ca bc s, do thnh phn v
liu lng cc dc cht c thay i ty theo th trng bnh,
em li hiu qu iu tr tt hn. Tuy nhin, vic bo ch
theo n i hi ngi dc s phi c kin thc v k thut
bo ch cng nh thc trch nhim cao m bo cht lng ca thnh phm:
Nguyn tc cn phi thc hin khi pha ch theo
n:
Kim tra n thuc m bo ng cc quy ch v
khng sai st v chuyn mn vi 1 s ni dung nh sau:
1. Trong n thuc cn ghi r tn, tui, a ch bnh
nhn, lu thng tui ca bnh nhn tr em.
2. Tn dc cht, khi lng ch nh pha ch (nng ,
hm lng trong n thuc).
3. Liu lng ch nh, ng dng, cch dng m bo an
ton hp l.
4. Thnh phn v ch nh ca n thuc c vi phm
cc vn tng k, tng tc thuc hay khng.
5. Chc danh, a ch v ch k ca ngi k n.
6. Ngy k n (ngy k tn trn n thuc).
7. Mu n thuc c m bo tnh hp php theo quy
ch hin hnh hay khng.
8. Ngi pha ch cn thc hin ng k thut bo ch,
ch m bo ng quy ch v nhn v bao gi.

28

9. Lu n thuc vo s theo di m bo cng tc

theo di qun l, thanh tra dc ca c s pha ch cng nh ca
cc c quan choc nng qun l ca ngnh.
Kim nghim thuc ung dng lng
6.1. nh ngha
Thuc ung dng lng l cc ch phm lng ng nht,
thng l dung dch, cn thuc, hn dch hoc nh dch ca
mt hay nhiu hot cht trong cht dn thch hp.
6.2. Yu cu k thut v phng php th.
6.2.1. Tnh cht:
Th cht, mu sc, mi v ty theo tng chuyn lun.
Cch thc: bng cm quan.
6.2.2. trong:
Thuc ung dng dung dch phi t yu cu v trong
theo tng chuyn lun.

6.2.3. Th tch:
Cch xc nh: Ging nh i vi thuc nh mt.

29

Th tch thuc phi nm trong gii hn cho php theo

bng 5.9.
Bng 5.9. Gii hn cho php th tch thuc ung
dng lng
Dng thuc

Th tch ghi trn % chnh lch

nhn
Ti 20 ml

Thuc nc ung

Trn 20 ml - 50 ml

+ 8%

Trn 50 ml - 150 ml

+ 6%

Trn 150 ml

+ 4%

Ti 100 ml
Siro

+ 10%

Trn 100 ml - 250

ml

+ 10%
+ 8%
+ 6%

Trn 250 ml
6.2.4. pH:
Mt s ch phm c yu cu th pH phi nm trong gii
hn quy nh

30

o bng my o pH
6.2.5. nhim khun:
nhim khun phi t gii hn quy nh cho ch phm
theo tng chuyn lun.
Cch th: Nu khng c quy nh ring th tin hnh th
v nh gi theo "Th gii hn vi sinh vt".
6.2.6. T trng:
T trng ca ch phm phi nm trong gii hn quy nh
theo tng chuyn lun.
Cch th: theo "Xc nh t trng cht lng".
6.2.7. ng u hm lng:
Mt s ch phm yu cu th phi tin hnh php th
ny
Cch th v nh gi ging nh i vi thuc bt.
6.2.8. nh tnh
Tin hnh nh tnh theo cc phng php c quy nh
trong tiu chun, ch phm thuc phi cho cc phn ng ca
cc hot cht c trong ch phm.
6.2.9. nh lng.
Ly thuc ca 5 n v ng gi nh nht bt k, trn
u. Tin hnh nh lng theo cc phng php ng gi c
quy nh trong tiu chun, hm lng ca tng hot cht trong
ch phm phi nm trong gii hn cho php theo bng 5.10.
Bng 5.10. Gii hn cho php v hm lng i vi
thuc ung dng lng
Dng thuc

% chnh lch

Thuc c A, B

5%

Thuc thng

10%

31

6.3. Cc dng thuc ung dng lng

Thuc ung dng lng phi t yu cu tiu chun k
thut chung i vi thuc ung dng lng v yu cu ring ty
tng chuyn lun.
6.3.1. Cn thuc:
Cn thuc l nhng ch phm lng c iu ch bng
cch ngm chit dc liu thc vt, ng vt hoc bng cch
ho tan cao thuc, dc cht theo t l quy nh trong ethanol
cc nng khc nhau.
6.3.2. Siro
Siro l dung dch m c (khng di 60%) ca ng
trng (sucrose) trong nc, c cha cc dc cht hoc cc dch
chit t dc liu v cc cht lm thm.
6.3.3. Potio
Potio l dng thuc nc c v ngt, cha mt hay nhiu dc
cht, dng ung tng tha. Potio c th dng hn dch hoc
nh dch.
Dung mi ca potio c th l nc, nc thm, nc hm hay nc sc dc liu. Potio thng cha 20% siro.
6.3.4. Dung dch ung (Oral solution)
Dung dch ung l nhng ch phm lng trong sut, cha
mt hay nhiu dc cht ha tan trong mt dung mi hay hn
hp nhiu dung mi thch hp dng bng cch ung.
Dung mi ca dung dch c th l nc, du, ethanol,
glyxerin...
6.3.5. Thuc ung git (Oral drop)
Thuc ung git l thuc ung c dng vi th tch nh
bng dng c phn liu l ng nh git.
6.4. Dung dch thuc dng ngoi dng lng.
Thuc dng ngoi dng lng l cc ch phm lng ng
nht, thng l dung dch, cn thuc, hn dch hoc nh dch

32

ca mt hay nhiu hot cht trong cht dn thch hp dng

ngoi.
Cc thuc dng ngoi dng lng phi t theo cc yu cu
k thut chung ca thuc ung dng lng v ring tng dng
thuc c nhng yu cu ting.

Phn III: Kt lun

Hin nay vic ng dng thuc dng dung dch vo vic
phng v tr bnh ngy cng c m rng c trong nhn y
v th y. Chnh v vy nghin cu v pht trin cng ngh
bo ch thuc dng dung dch l mt trng tm ca ngnh dc by gi v trong tng lai.

33