Q u a n ly - T r a o doi
Nghien cuu bao che vien nen paracetamol hai lop giai phong ngay va giai phong keo dai
Dat van de
Paracetamol la lya chgn d i u tien trong dieu trj cac trieu chung dau va sdt. Tuy nhien, h i u h i t cac c h i p h i m dd d i u bao c h i dudi dang giai phdng ngay de dap ipng muc dich giam dau, ha sdt tipc thdi cho ngudi benh, cdn trong nhCpng trudng hgp benh nhan dau hay sdt keo dai (sdt do virus) thi benh nhan lai phai SLP dung nhilu liiu. Dieu nay gay khdng it khd khan va phiin ha cho ngudi benh. Tren t h i gidi da cd vien nen paracetamol hai Idp giai phdng ngay va keo dai, vdi biet dugc la tylenol®. Nhung tai Viet Nam thi chua cd cdng ty dugc p h i m nao san xuit. Vi vay, chiing tdi dat v i n d l : "Nghien ciru bao che vien nen paracetamol hai lap giai phong ngay va keo dai"
Tip khoa: Vien nen 2 Idp, paracetamcl, giai phdng ngay va giai phdng keo dai.
Nguyen lieu va phu'o'ng phap nghien
CLFUNguyen lieu
Paracetamol sieu mjn, lactose, avicel PH 101, polyvinyl pyrolidon (PVP K30), sap ong, natri starch glycolat (S.S.G.), acid stearic, magnesi stearat va talc: dat tieu chuan Dugc dung. Vien doi chilu: vien nen tylenol® 8 hour 650 mg (McNeil Consumer Helthcare, USA), so Id PFM017, han SLP dung 04/2010.
Thilt bj nghien CLFU
May do dd i m Precisa XM 60, may thip do hoa tan ERWEKA DT60, may do quang pho UV-VIS VARIAN CARY 100, can phan tich MettlerAB204-S.
Phu'o'ng phap nghien cieu
Phwang phap bao che vien nen hai lap paracetamol
Lop giai phong ngay - lap 1: Bae c h i theo phuang phap xat hat udt.
Lap giai phong keo dai - lap 2: Bao c h i theo phuang phap tao hat ndng chay, nhiet do 60 - 65°C.
Nguyen Ngoc Chien. Tran Duy Giao Tnrnvg dai hoc Dime Ha Noi
Dap vien: Dap ldp 1 (400 mg) vdi lye dap 0,5-1,5 t i n ; dap ldp 2 vao ldp 1 (600 mg) vdi lye dap 1,5-2,5 t i n , dp day ciia vien 6,16±0,03 mm,, dudng kinh vien 10,0 mm tren may Pye Unicam.
Cac phwang phap danh gia tieu chuan chat Iwo'ng
Danh gia cac chf tieu cua hat
- Danh gia dp tren chay cua hat: tren may do do tran chay ERWEKA GWF, khdi luang hat la 40g, dudng kinh phdu 12mm.
- Oanh gia he sd Carr: He sd Carr dugc tinh theo cdng thiPC '^ ^':
C = P'~P' xlOO%
Trong dd p, = ty trgng thd, va pb = ty trpng bieu kiln xac djnh tren may do ty trgng bieu kiln ERWEKA SVW, gd vdi t i n so la 100 lin/phut trong thdi gian la 50 giay.
Danh gia cac chf tieu cua vien
- Danh gia dp CLPng, dp mai mdn: theo phuang phap chung ddi vdi vien nen.
- Djnh lugng paracetamol trong vien: theo phueng phap do quang, d budc sdng 242 nm, dung mdi la dung djch HCI 0,1N pH 1,2; ndng do khoang 10 |ig/ml.
- Thu- nghiem hoa tan
- May canh khuiy, tdc dp khuiy: 100 ± 2 vdng/phut.
- Mdi trudng hoa tan: 900 ml dung dich HCI 0,1NpH1,2. • '
- Nhiet dd mdi trueng: 37 ± 0,5°C.
Sau cac khoang thdi gian n h i t djnh, hut m i u , Idc, pha loang 50 l i n b i n g dung djch HCI 0,1N pH 1,2 va do mat do quang tai budc sdng 242 nm (n =3).
Sip dung he sd sai khac /s de so sanh hai dudng cong.
r,(% )= 50 X log 1 + - ! - £ (R , - T,y X 100
TAP CHI DUOC HOC - 03/2010 (SO 407 NAM 50)
Nghien CLFU - Ky thuat
Trong dd n = sd d i l m I i y mau; R|: p h i n tram paracetamol giai phdng tai thei d i l m t cua m i u doi chilu; T,: p h i n tram paracetamol giai phdng tai thei diem t ciia mau thip.
Hai do thj dugc coi la tueng dugng nhau n l u 50 < / 2 < 1 0 0 ' ^ ' ' ' .
Cac k i t qua nghien ciPu d u g c b i i u thj dudi dang: gia tri trung binh ± dp lech c h u i n va sip
dung p h i n m i m S-plus 6.0 d l so sanh hai m i u . K e t q u a n g h i e n CCPU v a b a n l u a n A n h hu'ang ciia ty le lactose trong cong thii'c
Cdng thiPC ldp giai phdng nhanh va cac cdng thiPC vien nghien cipu d u g c trinh bay d bang 1 va 2 tugng ipng.
B a n g 1 : C d n g thuc lap giai phong ngay (me 50 vien)
Thanh phan Paracetamol Avicel PH 101
PVP K30
Talc va Magnesi stearat (2:1) Nu'dc cat
Khoi Iwo'ng 325 mg
65 mg 8 m g
1 % khoi \wang hat kho 0,16 ml
Bang 2: Cdng thuc vien nghien cuu (me 50 vien)
L&p 1 Paracetamol
Sap ong , . „ Acid stearic
Lactose Avicel PH 101
Ta d u g c tran
CT1 Xem bang 1
325 20 45
-
205 1 % KLH
Khoi Iwo'ng (mg/vien) CT2
Xem bang 1 325
20 45 10,25(5%) 194,8(95%)
1 % KLH
CT3 Xembang 1
325 20 45 20,5(10%) 184,5(90%)
1%KLH
CT4 Xembang 1
325 20 45 30,75(15%) 174,3(85%)
1%KLH Ta duxrc tran la talc: magnesi stearat = 2:1: KLI-I = I<h6i luKyng hat sau l<hi sCra
Cac hat dugc bao c h i tip ldp 2 d i u cd tdc dd nay d i u cd kha nang tren chay tot. Ham lugng tran chay Idn han 10 g/giay, va he so Carr d i u dugc c h i t trong cac cdng thiPC d i u tren 97% va n i m trong khoang (15,25), cd nghTa la cac hat dd mai mdn dudi 1,0%. K i t qua dp cipng ciia dugc bao c h i theo phugng phap ndng chay vien 2 lgp CT1 the hien trgng bang 3.
Bang 3: Do cung cua vien tai cac luc dap khac nhau (n = 10) Lwc dap vien (tan)
(L&p 1: L&p 2) 0,5 : 1 0,5 : 1,5 0,5 : 2 1 : 2 1 : 2,5 1,5:2,5 06 ci>ng (N) 97,6 ±5,7 157,0 ±5,3 182,7 ±8,1 180,3 ±3,5 212,7 ±7,4 206,0 ±7,5 Ddi vdi vien nen hai Idp, Idp thip nhit dugc
dap vdi lye nen nhd nhit cd the va ldp thip 2 dugc dap vdi lye nen thich hgp d l dam bae dp CLPng cua vien. Bang 3 cho thiy khi lye dap Idp 2 tang thi dp cipng ciia vien tang. Treng t i t ca cac lye dap dugc khao sat thi lye dap lgp 1 : lgp 2 = 0,5 : 1,5 (tin) cho do cipng vien 157,0 ± 5,3 (N) la phu hgp. Do vay, lye dap ldp 1: lgp 2 = 0,5 : 1,5 (tin) dugc lya chgn d l tiip tuc nghien CLPU.
Kit qua thip hoa tan vien nen theo cac cdng thiPc g bang 2 dugc t h i hien tren hinh 1 (trang ben).
K i t qua thip dp hda tan cua vien nen theo cdng thuc g bang 2 cho thiy sau 10 phiit, da cd tren 45% dugc chit da dugc giai phdng t u cac
m i u nghien ciPU (khgang 90% dugc c h i t d ldp giai phdng ngay). Ddi vdi ldp 2, khi ham lugng lactose tang tip 0% (CT1) d i n 10% (CT3), toe do giai phdng dugc c h i t ciia cae cdng thiPC tueng ipng dugc cai thien dang k l . Tuy nhien, khi ham lugng cua lactose lep 2 tang len d i n 15 % (CT4) thi t i c dp giai phdng paracetamol lai giam. Dieu nay cd t h i do diing nhilu lactose lam keo dai thdi gian ra cua vien. Trong cac cdng thiPC tren thi CT3 cd dudng ccng giai phdng g i n vien ddi chilu nhit (f2 = 57,54). Tuy nhien t i e dp giai phdng dugc chit tip CT3 a cae thdi d i l m c u l l cdn thip hgn so vdi vien d i i chilu, nen ta dugc sieu ra dugc sip dung theo cae cdng thiPC e bang 4.
8 TAP CHi DUOC HOC - 03/2010 (SO 407 NAM 50)
Nghien CLFU - Ky thuat
Bang 4: Cdng thuc lap giai phong keo dai vai ty le S. S. G va Avicel khac nhau
Thanh phan Khoi lwang (mg/vien)
Thanh phin khac Avicel PH 101
S.S.G
CT5 Xem bang 2 182,5(89%) 2,1 (1,0%)
CT6 Xem bang 2 181,4(88,5%)
3,1 (1,5%)
CT7 Xem bang 2 180,4(88%) 4,10(2,0%)
CT8 Xem bang 2 179,4(87,5%)
5,1 (2,5%) K i t qua thii- do hoa tan eiia cae edng thiPC bang 4 duge t h i hien a hlnh 2.
giai phdng
i 1
100 90 eo 70 60 50 40 30 20 10 0
f^'^
0 1 2
—•—Tylenol -S..-CT1 Then
^^.--^""--^
3 4 gian (h)
CT2 CT3 5
CT4
—'''i
6
Thoi gian (h)
- T y l e n o l - » _ C T 5 , CTS - CT7 CT8
Hinh 1 : Dd thi giai phong paracetamol tu cac vien Hinh 2: Dd thj giai phong paracetamol tw c^c vien thir CO ty le lactose khac nhau thir co ty le S. S G khac nhau
K i t qua cho t h i y S.S.G da cai thien rd ret kha nang giai phdng d u g c c h i t ra khdi vien.
Phin tram giai phdng d u g e c h i t tai tipng thgi diem tang vdi ham lugng eiia ta durac ra S.S.G tang (p < 0,05) trip cac thdi d i l m da bao hoa duge c h i t va thdi d i l m 5 phiit ddi vdi CT5 va CT6 Khi ldp thip hai cd t i e dp ra nhanh hen cung thuc d i y qua trinh tach ldp vien nen lam giai phdng duge c h i t nhanh g thd'i d i l m d i u . Sau 5 phut cae vien da giai phdng tren 50%
luang paracetamol. Toe do hda tan duac c h i t da duac cai thien r i t nhi§u d- thdi d i l m d i u la do sip dung paracetamol dang bdt sieu mm (kich thudc t i l u phan duge c h i t nhd hgn 5
|im). Trong cac cdng thiPC tren CT6 ed dudng ccng giai phdng duge c h i t r i t g i n vdi dudng cong giai phdng tip vien ddi c h i l u (f2 = 80,77).
Ket luan
Lactose, avicel va natri starch glycolat cd anh hudng d i n sy giai phdng duge c h i t tip vien nen hai Idp paracetamcl giai phdng ngay va giai phdng keo dai. Cdng thiPC CT6 ed dudng cong giai phdng d u g c c h i t g i n n h i t vdi vien tylenol® ddi chilu.
Summary
Formulation of two-layered instant-release and sustained-release tablets of paracetamol.
Influence of the excipients including lactose, avicel, sodium starch glycolate on the drug release of the formulated tablets were studied.
Both lactose and sodium starch glycolate remarkably influenced the rate of drug release.
The dissolution profile of the chosen formulation, CT6, was similar to that of tylenol® tablets.
Tai lieu tham khao
1. Gereg, G.W. and Cappola, M. L.; Roller Compaction Feasibility for New Drug Candidates, Pharmaceutical Technology, 2002, 14-23.
2. Gil, EC. et al; Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrocholoride; International Joumal of Phannaceutics; 2006, V. 317, 32- 39.
3. Hasegawra, M.; Direct Compression Microctystalline Cellulose Grade 12 versus Classic Grade 102, Pharmaceutical Technology, 2002, 50-60.
4. Missaghi, S.; Fassihi, R., Release characterization of dimenhydrinate from an eroding and swelling matrix:
selection of appropriate dissolution apparatus; International Joumal of Pharmaceutics, 2005, V. 293, 35 - 42.
TAP CHI DUOC HOC-03/2010 (SO 407 NAM 50)