I HC Y DC THNH PH H CH MINH

KHOA DC

B MN BO CH

CNG THC TP
BO CH 2

Tn bi thc tp: Hn dch Thuc m Thuc n

t thc tp: 2

Nhm thc tp: 4

Bui thc tp: sng th 2

Bn thc tp: 3 Tiu nhm: 5

Lp: Dc 2013 Nin kho: 2016 2017

3/2017
 CNG THC TP BO CH 2
HN DCH THUC M - THUC N

Danh sch sinh vin Tiu nhm 5 Nhm 4

STT H tn sinh vin

1 Trn Gia Lc

2 Nguyn Duy Long

3 ng Th Thu Linh

4 Trn Th Thu Linh

5 inh Th Nh Mai

1
 MC LC

HN DCH IBUPROFEN 3

I. TNH CHT, VAI TR CA CC CHT TRONG CNG THC ........................................ 3

II. NNG CHT GY TREO Na CMC .................................................................................. 5

III. CNG THC HON CHNH V CCH IU CH .............................................................. 5

IV. NHN THNH PHM .............................................................................................................. 6

V. CC CH TIU KIM NGHIM HN DCH IBUPROFEN TRONG DC IN M

....................................................................................................................................................... 7

VI. THC HNH NH GI VAI TR CA Na CMC ............................................................... 7

THUC M DICLOFENAT 1% 9

I. TNH CHT, VAI TR CA CC CHT TRONG CNG THC ......................................... 9

II. THIT LP CNG THC ....................................................................................................... 10

III. CCH IU CH ..................................................................................................................... 11

IV. NH GI DN MNG V BN VT L CA SN PHM ............................. 12

V. CH PHM THUC M DICLOFENAC THAM KHO ..................................................... 13

THUC N PARACETAMOL 14

I. CC NI DUNG CN THC HIN ....................................................................................... 14

II. CCH THC HIN CC NI DUNG .................................................................................... 14

III. TNH CHT CA T DC PEF .......................................................................................... 18

IV. CCH IU CH THUC N ............................................................................................ 19

V. CH PHM THUC N PARACETAMOL THAM KHO .............................................. 20

K HOCH THC TP 21

2
I. TNH CHT, VAI TR CA CC CHT TRONG CNG THC

Thnh phn Tnh cht tan Tng k Vai tr

Ibuprofen Bt kt tinh trng / tinh th Khng tan: nc Hot cht chnh gim au,
khng mu khng vim, h st
D tan: aceton, dicloromethan,
methanol, ether
Tan: cc dung dch hydroxyd
kim long v carbonat kim

Saccharose Bt kt tinh trng / tinh th D tan trong nc theo t l Dung dch acid lm thy phn Cht iu v (lm ngt)
trng hoc khng mu, kh, o saccharose
1 : 0,5 (20 C) Cht gy treo, tng nht
bng o
1 : 0,2 (100 C)
Dung dch saccharose trong
nc c nht cao

Sorbitol Bt kt tinh trng, a hnh Rt d tan: nc (1 : 0,5) To phc chelat vi kim loi a n nh hn dch, ngn
ha tr saccharose kt tinh
t tan: ethanol 96%
To sp hoc gel khi khuy trn
mnh vi PEG
Lm mt mu oxid st
Tng phn hy penicillin

Natri CMC Dng ht, bt mn trng Tan: nc mi nhit Acid mnh, mui st v mt Cht gy treo
s kim loi (nhm, thy ngn,
Khng mi, khng v Khng tan: aceton, ethanol
km)
95%, ether v toluen
Gm xanthan

3
 Acid citric Bt kt tinh trng / tinh th Rt d tan: nc Kali tartrat, mui kim ca iu chnh pH
/ dng ht khng mu, c carbonat, bicarbonat, acetat,
D tan: ethanol 96% iu v (to v chua du d
th thng hoa sulfat
ung)
Hi tan: ether
Cht oxi ha, kh ha, cht c
tnh kim, mui nitrat

Natri benzoat Bt kt tinh / tinh th D tan: nc Gelatin, mui st, mui calci, Cht bo qun
trng, hi ht m mui kim loi nng (bc, ch,
Hi tan: ethanol 90%
thy ngn), kaolin

Dinatri edetat Bt kt tinh trng hay Khng tan: cloroform, ether Cht oxi ha mnh, base Cht to chelat
khng mu, v hi chua mnh, ion kim loi, hp kim
Tan t: ethanol 95%
Tan 1 : 11 trong nc

Vanilin Bt / tinh th hnh kim, Kh tan: nc lnh Aceton Cht thm (iu hng)
trng hay vng nht,
D tan: cn cao , nc nng
Mi c trng, v ngt

Tween 80 Cht lng trong, dng du Hn ha vi nc, ethanol, Mt mu hoc kt ta vi mt Cht din hot, gy thm
mu vng hay vng nu ethyl acetat, methanol s cht nh phenol, nha,
tannin
T trng tng i khong Thc t khng tan trong cc
1,08 du bo, parafin lng

Nc tinh khit

4
 HN DCH IBUPROFEN

CNG THC

Cng thc ca 1 n v phn liu 5 ml (cha 200 mg hot cht Ibuprofen):

Ibuprofen 000
Saccharose 040%
Sorbitol 006%
Natri CMC 000
Acid citric 00,2%
Natri benzoat 00,1%
Dinatri edetat 00,1%
Vanillin 0,01% (bt vanillin 10%)
Tween 80 00,2%
Nc tinh khit v 000

II. NNG CHT GY TREO Natri CMC

Natri CMC trong cng thc c vai tr nh mt tc nhn gy treo.

Theo Remington, Natri CMC ty thuc vo dng iu ch, cch s dng dng trong hay dng
ngoi m chn nhng nng khc nhau. nng thp c tc dng nh cht bo v keo, cn nng
cao th s c chc nng nh tc nhn tng tnh do.
Nng Natri CMC khong 0,25 1% l ph hp lm cht gy treo.
V vy tiu nhm ngh nng Natri CMC s dng l 1%.

III. CNG THC HON CHNH V CCH IU CH

1. Cng thc hon chnh

1 n v phn liu 5 ml, cha 200 mg Ibuprofen.

1 n v sn phm (cha 20 liu) c th tch 100 ml, cha 4 g Ibuprofen.
M hm lng ca Ibuprofen trong nguyn liu Ibuprofen l 98%, vy lng nguyn liu
Ibuprofen cn s dng cho 1 n v sn phm l:
100
4 4, 082 (g)
98

1 n v phn liu (5 ml) cha 0,01% vanillin, tc l 0,5 mg vanillin.

Nn 1 n v sn phm (100 ml) s c 0,01 g vanillin.
y l lng cn nh, kh thao tc. V vy, thay bng bt vanillin 10%.
100
Lng bt vanillin 10% cn dng cho 1 n v sn phm l: 0, 01 0,1 (g)
10

5
Cng thc honh chnh cho 1 n v sn phm

Ibuprofen 4,082 g
Saccharose 40 g
Sorbitol 6g
Natri CMC 1g
Acid citric 0,2 g
Natri benzoat 0,1 g
Dinatri edetat 0,1 g
Bt Vanillin 10% 0,1 g
Tween 80 0,2 g
Nc tinh khit v 100 ml

2. Cch iu ch

Phng php iu ch: phn tn c hc.

Nghin kh: tit trng ci chy, cn 4,082 g Ibuprofen vo ci, nghin mn.

Nghin t: cn 0,2 g Tween 80 trn mt knh ng h, cho t t vo ci s trn, trng mt knh

ng h vi mt t nc tinh khit ( 1 2 ml), trn u thnh khi nho.

To cht dn:
Cn 0,1 g natri benzoat, cho vo becher 50 ml ong sn 30 ml nc ct, khuy u cho
tan. Cho tip 40 g ng saccharose vo becher, khuy cho tan hon ton trn bp cch thy.
Sau ngui.
Ha tan ln lt 6 g sorbitol, 1 g natri CMC, 0,1 g dinatri edetat vo hn hp saccharose
trn, c hn hp A.
Cn 0,1 g acid citric ha tan vi 5 ml nc trong becher 50 ml, sau thm 0,1 g bt vanillin
10% vo cc, khuy u cho tan trn bp cch thu, c hn hp B.

Phn tn vo cht dn: cho t t hn hp cht dn A vo khi nho trong ci, phn tn u, cho
tip hn hp B vo, trng dng c bng mt t nc ri phn tn n ng nht.

Chuyn ton b hn hp trong ci vo chai ( c nh du th tch 100 ml), trng ci vi mt

t nc tinh khit.

B sung nc tinh khit va n vch 100 ml, lc u.

ng chai, dn nhn thnh phm.

6
 Nghin kh Nghin mn Ibuprofen trong ci

Nghin t Nghin trn u Ibuprofen vi Tween 80, mt

t nc tinh khit va to khi nho

Phn tn vo cht dn To cht dn

Thm t t cht dn vo ci, trn u

ng chai

IV. NHN THNH PHM

KHOA DC I HC Y DC TP. HCM

41 inh Tin Hong, Qun 1, TP. H Ch minh
HN DCH
IBUPROFEN 200 mg / 5 ml
Chai 100 ml
Cng thc:
Ibuprofen 4,082 g Ngy SX:
T dc v 100 ml Hn dng:
Cng dng: gim au, khng vim S l SX:
Cch dng: SK:
Bo qun:
LC K TRC KHI DNG
c k hng dn s dng trc khi dng

V. CC CH TIU KIM NGHIM HN DCH IBUPROFEN THEO DC IN M

Chuyn lun Ibuprofen Oral Suspension, USP 32

ng u hm lng: hm lng Ibuprofen (C13H18O2) khng c t hn 90,0 % v khng
vt qu 110,0% so vi hm lng ghi trn nhn.
nh tnh
ha tan
ng u ca n v phn liu
Th tch phn b
pH phi t 3,6 dn 4,6
Gii hn tp cht C: 4isobutylacetophenone

7
VI. THC HNH NH GI VAI TR CA Natri CMC

nh gi vai tr ca Natri CMC trong cng thc ta iu ch 2 cng thc: (1) c cht gy treo
Natri CMC, (2) khng c cht gy treo Natri CMC.

Thnh phn Cng thc 1 Cng thc 2

Ibuprofen 4,082 g 4,082 g
Saccharose 40 g 40 g
Sorbitol 6g 6g
Natri CMC 1g
Acid citric 0,2 g 0,2 g
Natri benzoat 0,1 g 0,1 g
Dinatri edetat 0,1 g 0,1 g
Bt Vanilin 10% 0,1 g 0,1 g
Tween 80 0,2 g 0,2 g
Nc tinh khit v 100 ml v 100 ml

Sau khi iu ch 2 cng thc trn, yn 24 gi cho hn dch n nh, sau ta nh gi kh

nng tch lp ( lng) v ti phn tn ca hai hn dch.

Theo DVN IV yu cu: hn dch khi yn th dc cht rn phn tn c th tch ring nhng
phi tr li trng thi phn tn ng nht trong cht dn khi lc nh trong 1 2 pht v gi nguyn trng
thi trong vi pht.

Cng thc 1 Cng thc 2

Kh nng
ti phn tn

t= pht t= pht

lng t= t=
t= t=

TI LIU THAM KHO

1. L Th Thu Vn, Hn dch Nh tng, Bo ch v Sinh dc hc Tp 2, NXB Y hc, 2014, tr. 2740.
th
2. Raymond C Rowe, Paul J Sheskey and Marian E Quin, Handbook of Pharmaceutical Excipients, 6 ed.,
Sucrose, Sorbitol, Carboxymethyl cellulose Sodium, Citric acid Monohydrat, Sodium Benzoate,
Disodium edetate, Vanillin, Polyoxyethylene Sorbitan Fatty Acid Esters, p. 703707, 679682, 118
121, 181183, 627629, 242244, 760761, 549553.
3. United States Pharmacopoeial Convention, Ibuprofen oral suspension, United States Pharmacopoeia 32,
2009, p. 26082609.
4. Philadelphia, PA. Lippincott Williams & Wilkins, Solution, Emulsions, Suspensions and Extracts,
st
Remington: The Science and Practice of Pharmacy, 21 ed., 2005, p. 756.

8
 THUC M DICLOFENAC 1%

CNG THC

Diclofenac diethylamin g
Sp ong g
Cetostearyl alcol g
Du parafin g
Propylenglycol 15 g
Tween 80 1g
Nipagin M 0,2 g
Nc ct v 100 g

I. TNH CHT, VAI TR CA CC CHT TRONG CNG THC

Thnh phn Tnh cht Vai tr

Diclofenac Bt kt tinh trng hoc hi vng, ht m nh Hot cht chnh, tc dng

diethylamin khng vim, gim au
D tan trong methanol, ethanol 96%; hi tan
trong nc; kh tan trong aceton
Dng mui Diclofenac diethylamin rt t tan
trong nc, tan tt trong pha du

Sp ong Th cht do hoc rn, trng hoc vng, c Thnh phn pha Du
Khng tan trong nc; t tan trong ethanol 96% Tng c, chy ca
3 thuc m
T trng : 0,95 0,96 g/cm
o
Nhit nng chy: 61 65 C

Cetostearyl Dng ht, vy, ging khi sp, hi vng Thnh phn pha Du
alcol
Khng tan trong nc. D tan trong ether, Cht nh ha, tng
ethanol 95% v ether du ha nht, n nh nh tng
o Lm mm da
Nhit nng chy: 49 56 C

Du parafin Dng lng, mu trng, khng mi v Thnh phn ca pha Du

Khng tan trong nc; t tan trong alcol; tan Gip iu chnh th cht
trong dung mi khng phn cc. ca thuc m
ng tan vi mi t l du bo
o 3
T trng (20 C): 0,84 0,89 g/cm

9
 Propylenglycol Cht lng, nht, khng mu, khng mi, v ngt Thnh phn pha Nc
Hn ha vi nc. Ha tan tinh du nhng Dung mi ha tan
khng hn ha vi du bo Diclofenac diethylamin
Cht gi m

Tween 80 Cht lng dng du mu vng hoc vng nu Cht nh ha to nh

tng D/N
Hn ha vi nc, alcol, ethyl acetat; khng tan
trong du bo v paraffin lng
3
T trng: 1,1 g/cm .

Nipagin M Bt kt tinh trng hoc tinh th khng mu, Cht bo qun, chng
khng mi, bn vi nhit vi khun v nm mc
pht trin
D tan trong cn 95%, propylenglycol
Tan trong nc nng; t tan trong nc lnh

Nc ct Cht lng trong sut, khng mu, khng mi, Mi trng phn tn
khng v

II. THIT LP CNG THC

Theo yu cu bi, Diclofenac 1% l Diclofenac natri (M = 318,1), nhng nguyn liu s dng
l Diclofenac diethylamin (M = 369,3).

Vy lng Diclofenac diethylamin cn s dng l:

369,3
1 1,16 (g)
318,1

1. T l pha du 15%

Tng khi lng pha Du trong cng thc l: 100 x 15% = 15 (g)

T l Sp ong: Cetostearyl alcol : Du paraffin = 0,5 : 0,8 : 2,5

Vy khi lng tng thnh phn:

Sp ong 2g
Cetostearyl acol 3,2 g
Du paraffin 9,8 g

Lng nc cn dng: 100 (1,16 + 15 + 15 + 1 + 0,2) = 67,6 (g)

10
2. T l pha du 25%

Tng khi lng pha Du trong cng thc l: 100 x 25% = 25 (g)

T l Sp ong: Cetostearyl alcol : Du paraffin = 0,5 : 0,8 : 2,5

Vy khi lng tng thnh phn:

Sp ong 3,3 g
Cetostearyl acol 5,3 g
Du paraffin 16,4 g

Lng nc cn dng: 100 (1,16 + 25 + 15 + 1 + 0,2) = 57,6 (g)

Nh vy, ta c 2 cng thc hon chnh sau:

Cng thc 1 Cng thc 2

Thnh phn
(pha Du 15%) (pha Du 25%)
Diclofenac diethylamin 1,16 g 1,16 g

Sp ong 2g 3,3 g

Cetostearyl alcol 3,2 g 5,3 g

Du parafin 9,8 g 16,4 g

Propylenglycol 15 g 15 g

Tween 80 1g 1g

Nipagin M 0,2 g 0,2 g

Nc ct 67,6 g 57,6 g

III. CCH IU CH

Phng php iu ch: trn u nh ha

1. iu ch pha Du

Tng ng mi cng thc, cn cetostearyl alcol, sp ong, du parafin (dng a), cho vo cng 1
becher 100 ml (A).
o
un chy hn hp trn bp cch thy, khuy tan hon ton v duy tr khong 60 2 C .

11
2. iu ch pha Nc

Cn lng nc ct tng ng cng thc trong becher 100 ml (B).

Cn 1 g tween 80, 15 g propylenglycol, cho vo becher 100 ml (C), thm mt t nc ct (B), un
cch thy nh cho tan.
Cn 1,16 g diclofenac diethylamin, 0,2 g nipagin M, cho vo (C), khuy u cho tan.
o
Cho ht lng nc ct cn li trong (B) vo, t ln bp cch thy, duy tr 65 2 C .

3. Phi hp pha Du v pha Nc

Khi 2 pha Du v Nc u t nhit th phi hp t t (C) vo (A), nh nh tng.
Khuy trn lin tc bng my (10 pht x 1000 vng/pht) cho n khi ng nht.
ng tup, dn nhn.

Nguyn liu Du parafin, sp ong, Nguyn liu

pha Du cetostearyl alcol pha Nc 1 g tween 80 + 15 g PG + t nc ct

un cch thu nh

un chy cch thu 1,16 g diclofenac diethylamin

0,2 g nipagin M
Nc ct cn li
Duy tr
un cch thu
Duy tr

Pha Du Pha Nc

Phi hp t t

Khuy trn lin tc

ng tup

Thnh phm

IV. NH GI DN MNG V BN VT L CA SN PHM

Tin hnh sau t nht 24 gi thnh phm c n nh.

1. dn mng

Nguyn tc: o din tch tn ra ca mt lng thuc m nht nh khi cho tc dng ln n nhng
trng lng khc nhau.

Dng c: thc o, 2 tm knh nhn (15 x 15 cm), cc qu cn.

12
 Tin hnh: 2 mu vi t l pha du 15% v 25%. Mi mu thc hin 2 ln, mi ln nh sau:

St trng tm knh bng cn, kh t nhin.

Ly 2 tm knh, c nh du phn bit tm kinh di v tm knh trn.

Cn 1 g thuc m ln gia tm knh di, sau t tm knh trn ln khi thuc. Sau 1 pht o
ng knh tn ra ban u ca khi thuc.

t qu cn g ln gia mt tm knh trn. Sau 1 pht o ng knh tn ra ca khi thuc.

d
2
Tnh din tch tn ra ca khi thuc m theo cng thc: S
2
(mm ), vi d l ng knh tn ra
4
ca thuc m.

Pha du 15% Pha du 25%

Mu
0g Qu cn g 0g Qu cn g

d= d= d= d=
Ln 1
S= S= S= S=
d= d= d= d=
Ln 2
S= S= S= S=
S trung bnh
S

2. bn vt l

Nguyn tc: xc nh thi gian tch lp ca thuc bng phng php shock nhit.

Tin hnh: 2 mu vi t l pha du 15% v 25%. Mi mu thc hin nh sau:

Ly 1 ng nghim c np y, cho vo khong 8 g thuc m.

o
un trong bp cch thy 50 C, ghi nhn thi gian tch lp.
So snh s tch lp ca thuc m trong 2 cng thc trn.

Quy c: ghi nhn thi gian khi thuc m tch c 1 lp khong 0,8 cm.

Mu Pha du 15% Pha du 25%

Khi lng th

Nhit

Thi gian tch lp

13
V. CH PHM THUC M DICLOFENAC THAM KHO

Tn thuc Dophafenac 1% Diclofenac Sodium Gel

Hm lng hot cht 1% 3%

Nh sn xut DOPHARMA TOLMAR Inc.

Alcol cetylic Benzyl alcohol

Acid stearic Hydroxyethyl cellulose
Vaselin Methoxypolyethylene glycol 360
Propylen glycol PEG-60 hydrogenated castor oil
Thnh phn t dc Du parafin Nc tinh khit
Nipagin
Nipasol
Natri laurylsulfat
Nc ct

Cu trc ca thuc Nh tng D/N Nh tng D/N

TI LIU THAM KHO

1. Hunh Vn Ha, Hunh Trc Thanh Ngc, Thuc m, Bo ch v Sinh dc hc Tp 2, 2014, tr. 83
95.

2. B Y T, Dc in Vit Nam IV, 2009, PL 1.12.

th
3. Raymond C Rowe, Paul J Sheskey and Marian E Quin, Handbook of Pharmaceutical Excipients, 6
ed., Cetoacyl alcohol, Wax White, Propylene Glycol, Petrolatum, Polyoxyethylene Sorbitan Fatty
Acid Ester, Methyl Parapen, p. 150151, 779780, 592594, 481483, 549553, 441.

14
 THUC N PARACETAMOL

CNG THC

Paracetamol 150 mg
T dc v 1 vin
T dc bao gm PEG 4000 : PEG 400, t l 90 : 10

Yu cu: iu ch 24 vin thuc n Paracetamol t ch tiu v cm quan, r, ng u

khi lng.

I. CC NI DUNG CN THC HIN

Xc nh h s thay th ca Paracetamol vi hn hp t dc.

Tnh ton lng hot cht, t dc cn dng v thit lp cng thc iu ch 24 vin thuc.
nh gi cc ch tiu v cm quan, r, ng u khi lng.

II. CCH THC HIN CC NI DUNG

1. Xc nh h s thay th E

H s thay th (HSTT) thun E ca 1 cht so vi t dc l lng cht chim 1 th tch tng

ng 1 g t dc khi khun.

Hot cht Paracetamol v hn hp t dc PEG 4000 : PEG 400 c khi lng ring khc nhau
Hm lng hot cht Paracetamol trong vin l 0,15 g > 0,05 g
V vy, cn phi xc nh HSTT tnh lng t dc, nhm m bo cho mi vin thuc cha
ng lng dc cht theo yu cu.

Tin hnh:

Bc 1: iu ch 12 vin n t dc nguyn cht

Khun thuc n c th cha khi lng 1 3 g v cc ch phm thuc n trn th trng thng
1 vin 3 g. Nn tiu nhm ngh chn 3 g.

Lng t dc cn dng l: 12 x 3 = 36 (g)

tr hao, tiu nhm dng 40 g t dc.
Da vo t l PEG 4000 : PEG 400 = 90 : 10, vy:
PEG 4000 36 g
PEG 400 4g

Sau khi iu ch, em cn tng khi lng 12 vin t dc, ta c gi tr x (g).

15
 Bc 2: iu ch 12 vin thuc n c cha Paracetamol v hn hp t dc

T l dc cht qu ln s lm cho vin n b mm, d chy, gy kh khn cho vic ly ra khi

khun v cn.
Nn tiu nhm ngh iu ch vin thuc n cha 10% Paracetamol theo khi lng.

Lng Paracetamol l: 40 x 0,1 = 4 (g)

Lng hn hp t dc l: 40 4 = 36 (g)

Da vo t l PEG 4000 : PEG 400 = 90 : 10, vy:

PEG 4000 32,4 g
PEG 400 3,6 g

Sau khi iu ch, em cn tng khi lng 12 vin, ta c gi tr y (g).

Vin n t dc Vin n cha Paracetamol

nguyn cht v hn hp t dc
Paracetamol 0g 4g

PEG 4000 36 g 32,4 g

PEG 400 4g 3,6 g

Bc 3: Tnh h s thay th nghch F

x y p
F
p

Vi x: khi lng 12 vin t dc nguyn cht

y: khi lng 12 vin cha Paracetamol v hn hp t dc
p: khi lng Paracetamol c trong 12 vin, tnh theo y

Do lng Paracetamol chim 10% theo khi lng vin, nn: p 0,1 y (g)

Vy cng thc tnh HSTT nghch c th l:

x y 0,1 y 10 x 9 y
F
0,1 y y

1
T , suy ra HSTT thun l: E
F

16
2. Tnh ton lng hot cht, t dc cn dng v thit lp cng thc

1 vin thuc n cha 150 mg Paracetamol.

Vy tng lng Paracetamol trong 24 vin thuc n l:
0,15 x 24 = 3,6 (g)

nb
Lng t dc c thm vo theo cng thc: X na
E
Trong E: h s thay th thun
n: s lng vin thuc cn iu ch (n = 24 vin)
x
a: khi lng ca 1 vin t dc, a (g)
12
b: khi lng dc cht cho 1 vin (b = 0,15 g)

Thay vo cng thc ta c tng lng t dc cn dng l:

24 x 24 0,15 3,6
X 2x (g)
12 E E

T l PEG 4000 : PEG 400 = 90 : 10 nn:

Lng PEG 4000: 0,9X (g)

Lng PEG 400: 0,1X (g)

Cng thc hon chnh iu ch vin thuc n Paracetamol

1 vin thuc n 24 vin thuc n

Paracetamol 0,15 g 3,6 g
PEG 4000 0,9X g 21,6X g
PEG 400 0,1X g 2,4X g

3. Cc ch tiu v cm quan, r, ng u khi lng

Cm quan

B mt vin phi mn, lng, khng c vt nt do lm lnh qu nhanh hay do lc khun qu sm

hoc qu mun.

Khng c c nhng m trng hoc s kt tinh dc cht trn b mt vin.

Khi ct dc v ct ngang vin thuc v quan st, mt ct phi thun nht, khng c hin tng
ng cc hay lng ng dc cht.

17
 Cm quan
Hnh dng
Kch thc
Mu sc
B mt
Rut (ct dc, ngang)

r (DVN IV, PL 11.5, tr. PL225)

Php th ny xc nh thuc n c r hoc mm i hay khng trong khong thi gian quy nh,
khi c t trong mi trng lng c nhng iu kin th nghim ch nh.

Thit b:
ng bao trong sut bng thy tinh hay cht do, cao 60 mm vi
ng knh bn trong 52 mm, thnh dy thch hp.
B phn kim loi gm 2 a kim loi khng g, mi a c 39 l trn,
ng knh 4 mm. ng knh ca cc a gn nh tng tng vi ng
knh bn trong ca ng bao. Hai a cch nhau khong 30 mm. B phn
kim loi c treo bng 3 mc kp cch u nhau, gn vo thnh ngoi ng
bao nh ch dn trong hnh.

Thit b th r ca thuc n
v thuc trng (kch thc tnh bng mm)

Cch th:

t 1 vin ln a di ca b phn kim loi, a b phn ny vo ng bao v gn cht vo thnh

o
ng. Nu khng c ch dn khc, t thit b vo bn cha t nht 4 L nc m (36 37 C) c gn dng
c khuy chm v gi thit b th v tr thng ng, ngp 90 mm so vi mt nc. Xoay ngc thit b
th 10 pht 1 ln, trnh khng nh ln khi mt nc.

Lp li ton b th nghim vi 1 vin khc.

Thuc c coi l r, khi p ng 1 trong cc yu cu sau:

Tan hon ton.

Phn tch ra cc thnh phn to thnh, ri tp trung trn b mt (cc cht m nng chy),
chm xung y (bt khng tan), hay ha tan trong nc (cc thnh phn ha tan), hoc c
th phn tn theo 1 hay vi cch nu trn.

Tr nn mm, c th bin dng ng k, khng nht thit b phn tch hon ton ra cc
thnh phn to thnh, nhng khng c nhn rn chu c sc p ca a thy tinh.

Thi gian r khng qu 60 pht i vi thuc n tan trong nc

18
 r M t
Thit b ng bao: , cao , ng knh trong , thnh dy
B phn kim loi: a kim loi, l trn, ng knh l
Cnh khuy:
Tin hnh S mu th:
Th tch nc:
Nhit :
Kt qu Vin 1: Vin 2: Vin 3:

ng u khi lng (DVN IV, PL 11.3, tr. PL221)

Cn ring bit 20 n v ly ngu nhin, tnh khi lng trung bnh.

Khng c c qu 2 n v c khi lng vt qu 5% so vi khi lng trung bnh vin v

khng c n v no c khi lng vt gp i gii hn (tc l vt qu 10%).

STT Kt qu STT Kt qu
Vin 1 Vin 11
2 12
3 13
4 14
5 15
6 16
7 17
8 18
9 19
10 20
Trung bnh:
Khong:

III. TNH CHT CA T DC PEG

PEG l t dc keo thn nc tng hp, c th hn ha vi cc PEG khc theo bt c t l no.

lm t dc thuc n, thng phi hp cc PEG th lng, mm v rn theo t l thch hp thu
c hn hp PEG c th rn hoc mm do nhit thng v tan chy nhit c th.

Cng thc: HOCH2(CH2OCH2)nCH2OH

19
 Tnh cht PEG 400 PEG 4000

Th cht Lng Rn

Phn t lng
380 420 3000 4800
trung bnh

im ng c (oC) 48 53 59

im chy (oC) 50 58

T trng (g/cm3) 1,120 1,080

nht (25 oC) 105 130 cP 110 170 cP

Tnh ht m Ht m mnh Khng ht m

Nhn, trong sut, khng mu hay Khng mu, khng v, c mi nh

vng nht, mi c trng, v ng ring
Ho tan c nhiu hot cht, k c ng tan vi nc, cn, aceton,
mt s cht khng tan trong nc v benzene v cc glycol
Tnh cht khc trong du
Khng ng tan vi du bo, ether
v cc hydrocarbon
C kh nng gy thm nh ho Khng dng ring bit lm t dc
cho thuc n

u im Nhc im

Khng gy nh hng sinh l ni t

thuc
Cc PEG rt bn vng, c th bo qun
d dng, c bit cc PEG khng phi
mi trng thun li nm mc pht
trin
C cng v chy cao nn c cho ngi s dng v gy au nu ch t
bn c hc ln hn cc t dc thuc
nhm t dc thn du
V vy cc PEG l t dc thch hp
vi iu kin kh hu nhit i
Tnh ht nc cao ca PEG s gy kch ng
trc trng hoc kch thch nhu ng rut,
lm vin thuc c th b y ra ngoi, c
th khc phc bng cch nhng vin thuc
vo nc trc khi s dng
Do c cng cao nn c th gy kh chu
thuc b thng
Gii phng dc cht chm v ha tan
chm trong nim dch

20
IV. CCH IU CH THUC N

Phng php: un chy khun

Nguyn tc: dc cht c ha tan hoc phn tn trong t dc c un chy, sau
vo khun c th tch nht nh nhit thch hp.
Phng php ny l phng php thng dng nht, c nhiu nc p dng c quy m
nh ln quy m cng nghip.

Tin hnh qua 2 giai on:

Chun b dng c v nguyn liu.
Phi hp dc cht vo t dc v khun.

1. Chun b dng c v nguyn liu

Dng c:
Ci chy: nghin Paracetamol.
Chn s: un chy PEG v ha tan Paracetamol.
a khuy.
Khun: tit trng bng cn, bi trn khun bng du parafin, sau lm lnh (p xung). Ch s
dng khi hn hp khun sn sng.
Tt c cc dng c phi c ra sch v tit trng.

Nguyn liu: Paracetamol, PEG 4000, PEG 400

2. Phi hp dc cht vo t dc v khun

Dc cht Paracetamol ( tan trong nc l 1 : 70, trong nc nng l 1 : 20), PEG l t dc

keo thn nc tng hp, do trong cng thc c 2 nhm OH phn cc nn ha tan c Paracetamol nn
s quyt nh loi cu trc ca ch phm l dung dch.

Phng php phi hp hot cht vo t dc: ha tan nng

Cc bc thc hin:

Phi hp dc cht vo t dc

Cn PEG 4000, Paracetamol ( c nghin mn) trn giy, cn PEG 400 trong chn s sau
cho PEG 4000 vo.

iu ch hn hp t dc: un hn hp t dc PEG 400 v PEG 4000 trong chn s trn bp

cch thy n khi chy hon ton, khuy u n khi hn ha vi nhau (ch khuy khi PEG 4000
chy ht trnh dnh ln dng c khuy), ch trnh to bt.
o
Phi hp Paracetamol vo hn hp: khi nhit xung khong < 60 C, cho Paracetamol vo,
va un va khuy u n khi tan hon ton (lm nhanh trnh Paracetamol thy phn c mu hng).

o
Nhc chn s khi bp (lt khn), tip tc khuy n khi h nhit xung khong 50 C th tin
hnh khun.

21
 khun
Ly khun, nhanh hn hp vo khun. Ch thao tc nhanh v lin tc trnh to ngn,
y v cao hn b mt khun 1 2 mm.
Lm lnh khun thuc ng rn hon ton.
Dng dao ct b phn tha, tho khun v ly thuc.
Gi vin trong giy chng m, dn nhn, bo qun kn, ni mt.

Chun b Paracetamol, PEG 4000 (trn giy), PEG 400 (trn chn s)
Chn s, a khuy, khun

iu ch hn hp t dc

un chy hon ton

Khuy u

Ho tan nng
o
< 60 C, cho Paracetamol vo, va un va khuy nhanh cho tan
o
< 50 C, em khun

khun

nhanh, lin tc, cao hn khun 1 2 mm

Lm lnh khun, thuc ng rn hon ton
Ct b phn tha, ly thuc

ng gi

V. CH PHM THUC N PARACETAMOL THAM KHO

Tn Hm lng T dc Cu trc

Biragan 150 150 mg Suppocire NAI 25 (thn du) Hn dch

Alvedon Suppositories
60 mg Witepsol H12 (thn du) Hn dch
60 mg

TI LIU THAM KHO

1. Trnh Th Thu Loan, Thuc t, Bo ch v Sinh dc hc Tp 2, 2014, tr. 105115.
th
2. Raymond C. Rowe, Paul J. Sheskey, Marian E. Quinn, Handbook of Pharmaceutical Excipients, 6
ed., 2009, p. 517521.
3. B Y T, Dc in Vit Nam IV, 2009, PL 1.10, PL 11.3, PL 11.5.

22
 K HOCH THC TP

Tun Ni dung thc tp

Tun 1 Sa cng
iu ch 2 cng thc hn dch Ibuprofen
Tnh ton hm lng hot cht, t dc thit lp cng thc iu
ch thuc n Paracetamol

Tun 2 Kho st cng thc thuc m

iu ch thuc m Diclofenac 1%
Kim nghim hn dch Ibuprofen

Tun 3 iu ch thuc n Paracetamol

Kim nghim thuc m Diclofenac 1%

Tun 4 Kim nghim thuc n

Tng kt

23
Ghi ch

......................................................................................................................
......................................................................................................................
......................................................................................................................
......................................................................................................................
......................................................................................................................