THUC

THUC PHUN
PHUN M
M

MC
MC TIU
TIU HC
HC TP
TP
1. Trnh by nh ngha, phn loi v u nhc im ca
thuc phun m.
2. Trnh by c thnh phn cu to ca cc dng thuc
phun m qua ng h hp.
3. M t c nguyn tc k thut bo ch thuc phun m.
4. Trnh by c yu cu cht lng thuc phun m.
5. Trnh by c mt s yu t nh hng n SKD ca
thuc phun m.

KHI
KHI NIM
NIM
Lch s:

KHI
KHI NIM
NIM
Aerosol (pressurized) mettered-dose inhaler ((p)MDI)
Nebulizer
Dry powder inhaler (DPI) inhalation powder
Spray
Medical Gases (Inhalation materials)
Foam spray
Powder spray

PHN
PHN LOI
LOI
Theo trng thi tp hp ca thuc v cht y
Theo ng dng
Theo cu trc ha l
Theo dng c, thit b to phun m

U,
U, NHC
NHC IM
IM
u im:

Dng BC s dng rt thun tin, d dng to ra

mt liu thuc khng cn dng c trung gian.
Thuc ng trong bnh kn, hn ch c cc tc
ng bt li ca MT nh KK, m, VSV.
Thuc phun ra c th ph nh trn da hay nim
mc b tn thng, hn ch tc ng gy au n
cho BN (thuc cha bng).

U,
U, NHC
NHC IM
IM
u im:

TPM dng ti ch c hiu qu cao do thuc tip

xc tt vi da, nim mc, hn ch tc dng khng
mong mun vi ton thn.
Mt s hormon dng dng ht qua ng HH c
hiu qu nh thuc tim m khng i hi iu
kin v khun cao nh thuc tim.
DC b phn hu ng tiu ho, chuyn ho
nhanh khi qua gan ln u, khi dng dng TPM
qua ng HH s c hiu lc cao do c hp
thu tt qua ph nang (insulin).

U,
U, NHC
NHC IM
IM
Nhc im:

Mt s phun m khi dng nhm cho ng h

hp c th gy tai bin cht ngi.
Do c im gii phu sinh l ca ng h hp
phn nhnh rt ln nn cc tiu phn khi di
chuyn trong ng th c th b bt gi theo cc
c ch khc nhau.

E. R. Weibel

Cu trc hnh cy phi.

Vng ph nang ct ngang.

Siu cu trc mng h hp (mt ct ngang)

MT
MT S
S BNH
BNH
NG
NG H
H HP
HP
Hen ph qun
Vim ph qun cp
Vim ph qun mn
Trn kh mng phi
Chng gin ph qun
Thiu cht din hot phi

MT
MTS
SNHM
NHMTHUC
THUCDNG
DNGQUA
QUANG
NGH
HHP
HP
Chng d ng (Anti-allergy agents)
Ch vn th th (Beta receptor agonists)
Adrenocorticosteroids
Leukotriene inhibitors
Cc thuc gin ph qun khc (bronchodilating
agents)
Thuc tiu m (Mucolytics)
Cc thuc c tc dng ton thn (Systemicallyabsorbed drugs)

BAO
BAO B
B THIT
THIT B
B A
A THUC
THUC MDI
MDI

BAO
BAO B
B THIT
THIT B
B A
A THUC
THUC MDI
MDI

BAO
BAO B
B THIT
THIT B
B A
A THUC
THUC MDI
MDI

BAO
BAO B
B THIT
THIT B
B A
A THUC
THUC MDI
MDI

Cu to v hot ng ca van phun nh liu

Cu to v hot ng ca van phun nh liu ci tin

Van phun nh liu vi spacer

Van phun nh liu vi spacer

Van phun lin tc

CHT
CHT Y
Y CHO
CHO MDI
MDI
Kh ha lng:

CFC
HFA
Isobutan
HFO (trans-1,3,3,3,-tetrafluoropro-1-ene (HFO
1234ze) v 2,3,3,3,-tetrafluoroprop-1-ene (HFO
1234yf))

Cht y l kh ha
lng

Cht y l kh nn

MDI
MDI H
H DUNG
DUNG DCH
DCH
Dc cht
Dung mi, ng dung mi:

Ethanol: tng tan, nh hng ti phn b

Cht tng tan
H m, cht iu chnh pH
Cht ng trng, iu chnh p sut thm thu
Bo qun (l, ha, sinh)
Cht lm tng phn b, hp thu
iu hng, iu v

MDI
MDI H
H HN
HN DCH
DCH
Dc cht t tan
Mi trng phn tn
Cht gy thm, n nh
H m, cht iu chnh pH
Cht ng trng, iu chnh p sut thm thu
Bo qun (l, ha, sinh)
Cht lm tng phn b, hp thu
iu hng, iu v

MDI
MDI H
H NH
NH TNG
TNG
DC lng ko tan trong dm/DC tan trong dm khc ko
ng tan vi MTPT
Mi trng phn tn
Cht nh ha, n nh
H m, cht iu chnh pH
Cht ng trng, iu chnh p sut thm thu
Bo qun (l, ha, sinh)
Cht lm tng phn b, hp thu
iu hng, iu v

THIT
THIT B
B A
A THUC
THUC -- NEBULIZER
NEBULIZER

Dng dng kh Dng siu m

Lc qua ry

Nebulizer

Nebulizers

DCH
DCH CHY
CHY KH
KH DUNG
DUNG -- NEBULIZER
NEBULIZER
Xem cc phn trc

THIT
THIT B
B A
A THUC
THUC -- DPI
DPI

DPIs

Single dose
(Rotahaler)

Multiple doses
(Turbuhaler)

Dry powder inhalers (DPI)

nh hng ca loi thit b ht bt kh n

s phn b thuc phi

CNG
CNG THC
THC THUC
THUC DPI
DPI
Dc cht
Cht mang
T dc khc: chng kt t (silic dioxyd keo khan).

Fig. 5. Scanning electron microscopy of Pearlitol 100 SD

blended with terbutaline sulphate.

Fig. 2. SEMs of original and surface

modified particles. (a) original PH, (b) PM
10%, (c) TC 10%, (d) FD 10%, (e) SD 10%.

Schematic representation of improvement of inhalation property by

the surface modification of pranlukast particles with AEROSIL.

K
K THUT
THUT BO
BO CH
CH MDI
MDI
Bo ch thuc np vo bnh:

p dng KT bo ch chung cho dung dch, hn

dch, nh tng thuc hoc dng bt thuc siu
mn.
ng np thuc v cht y vo bnh thuc:

ng p sut (Pressure filling).

ng lnh (Cold filling): ~ -50oF ko thun li.
ng y van ngay (Undercap filling).

Thuc BC
Thuc BC

Cht y l kh ha lng
(ng p sut)

Bnh, van,
Bnh, van,
vng m...
vng m...

ng kn
ng kn

Cht y
Cht y
(bnh chu a/s)
(bnh chu a/s)
Bo ha CO
Bo ha CO2 2
Phn tn
Phn tn
(bnh chu a/s)
(bnh chu a/s)
Np thuc
Np thuc
(a/s)
(a/s)
y u phun,
y u phun,
np...
np...

Hickey A. J. (2003), Pharmaceutical

inhalation aerosol technology, CRC
Press.

Thuc BC
Thuc BC

Cht y l kh ha lng
(ng lnh)

Cht y
Cht y

Bo ha CO
Bo ha CO2 2

Phn tn
Phn tn

Bnh cha
Bnh cha

Np thuc
Np thuc
o
(-50
F)
o
(-50 F)

Van, vng m,
Van, vng m,
u phun, np...
u phun, np...

ng kn
ng kn

Thuc BC
Thuc BC

Bnh cha
Bnh cha

Np thuc
Np thuc

Cht y l kh nn
(ng p sut)
Van, vng m...
Van, vng m...

ng kn
ng kn

Cht y
Cht y

Np kh (a/s)
Np kh (a/s)
y u phun,
y u phun,
np...
np...

K
K THUT
THUT BO
BO CH
CH DCH
DCH CHY
CHY
KH
KH DUNG
DUNG -- NEBULIZER
NEBULIZER
p dng KT bo ch chung cho dung dch, hn dch,
nh tng thuc.

K
K THUT
THUT BO
BO CH
CH DPI
DPI
Chun b dc cht
Chun b cht mang
Phi hp dc cht cht mang t dc khc
ng vo nang hoc thit b ht bt kh

TIU
TIU CHUN
CHUN CHT
CHT LNG
LNG
Ch tiu cht lng chung: Tnh cht, pH, nh tnh,
nh lng dc cht v tp cht lin quan (nu c), vi
sinh vt, sai s khi lng/th tch

TIU
TIU CHUN
CHUN CHT
CHT LNG
LNG
Kim tra ch tiu c trng:

chnh xc khi phn liu: Phun tng liu thuc

vo dung mi thch hp sau em nh lng
hoc cn bnh thuc trc v sau khi phun mt
s liu t tnh c KLTB ca liu thuc
Phn b KTTP: dng knh hin vi, my m tiu
phn, dng c phn tch KTTP theo tng va
chm (cascade impactor) nh gi KT kh lc
hc ca tiu phn m.

In vitro

Cascade impactor

In vitro

nh hng ca kch thc tiu phn n

s phn b thuc

V
V D
D
Dung dch chy kh dung Bricanyl: (nebulizer)
Terbutalin sulfat loi pha tim

100 mg

Natri clorid

580 mg

Dung dch acid hydrochloric 2M

v pH 3

Nc pha tim v

100 ml

V
V D
D
Dung dch chy kh dung Dornase-Alpha:
(nebulizer)
Dornase-Alpha

1,00 mg

Calci clorid dihydrat

0,15 mg

Natri clorid

8,77 mg

Nc pha tim v
pH ~ 6,3

1 ml

V
V D
D
Thuc phun m salbutamol beclomethason:
Thnh phn : (cho 1 liu)
Salbutamol sulfat (siu mn)

120 g

Beclomethason dipropionat

50 g

Acid oleic

12 g

Ethanol
HFA 134a

6 mg
60 mg

V
V D
D
Thuc phun m budesonid:
Thnh phn : (cho 1 liu)
Budesonid (siu mn)

0,20 mg

Acid oleic

0,02 mg

Ethanol

1,20 mg

HFA 134a

60,00 mg

V
V D
D
Thuc phun m mometason - formoterol:
Thnh phn : (cho 1 liu)
Mometason furoat (khan)

200 g

Formoterol fumarat (dihydrat)

5 g

Acid oleic

3 g

Ethanol
HFA 227

1,1 mg
60,00 mg

V
V D
D
Thuc phun m beclomethason:
Beclomethason dipropionat

1,6 g

Ethanol

35,2 g

Acid oleic

0,16 g

HFA 227

960 g

V
V D
D
Insulin Inhalation Spray:
10 g

Brij 98

9g

Natri laurylsulfat
H m pH = 7
Ethanol tuyt i
HFA 134a v

10 g
v
200 g
1L

ng kh

Insulin

V
V D
D
Fluticasone Suspension Spray:

Fluticason propionat

2,00 g

-Tocopherol

0,02 g

HFA 134a v

1500,00 g

V
V D
D
Oxitropium and Formoterol Nasal Spray:

Oxitropium bromid (bt siu mn)

4,500 g

Formoterol fumarat (bt siu mn)

0,675 g

HFA 134a v

10500,000 g

V
V D
D
Thuc phun m gim au, chng vim:
Methyl salicylat

10 g

Menthol

1g

Camphor

2g

Tinh du khuynh dip

0,2 ml

Propylen glycol

10 ml

Isopropanol 70%
Nitrogen

va 100 ml
v

V
V D
D
Thuc phun m gy t:
Polidocanol

1g

Kollidon VA 64 (PVP)

50 g

Ethocel 20 (EC)

50 g

Lutrol E 400 (PEG 400)

20 g

Ethyl acetat

675 g

Isopropanol

200 g

Propan hoc butan

V
V D
D
Thuc phun m st khun:

Povidon iod

100 g

Kollidon VA 64

150 g

n-Propanol

750 g

Ethanol

750 g

Propan hoc butan

V
V D
D
Thuc phun bt st khun:

Povidon iod

100,0 g

Cremphomor A 25

0,1 g

Nc tinh khit v

1000,0 g

Propan : butan (10 : 1)

V
V D
D
DPI (capsules):

Formoterol fumarat

12 g

Lactose (cht mang)

25 mg

V nang

1 chic

CT 1:
Salmeterol
HFA 134a

4,0 mg
v

(di dng salmeterol xinafoat)

Salmeterol
Ethanol
HFA 134a

4,0 mg
(1 5% CT)
v

Salmeterol
Ethanol
Acid oleic
HFA 134a

4,0 mg
(1 5% CT)
(0,001 0,5% salmeterol)
v

Salmeterol
Ethanol
Lecithin
HFA 134a

8,0 mg
(1 5% CT)
(0,001 0,5%)
v

Salmeterol
Ethanol
Acid citric
HFA 134a

8,0 mg
(1 5% CT)
(0,001 0,5%)
v

Salmeterol
Ethanol
HFA 134a

8,0 mg
(1 5% CT)
v

CT 2:

CT 3:

CT 4:

CT 5:

CT 6:

CT 7: Cho 1 vin nang cng

Salmeterol (siu mn) 26 50 g
Lactose (siu mn)
v