Nghien CLFU - Ky thuat
binh ± 5%; Thy dp hda tan (dp PTHC): Theo USP 29 (khdng dyge it han 5% va khdng dyge qua 30%
sau 30 phut, khdng dyge it han 20% va khong dyge qua 50% sau 60 phut, khdng dyge it han 80%
sau 240 phut); Djnh lygng: Ham lygng cefaclor (C15H14CIN3O4S.H2O) trong mdi vien phai dat tCp:
90,0% - 110,0%, so vdi ham lygng ghi tren nhan, tinh theo khii lygng trung binh vien; Bao quan: trong bao bl kin, de nai khd mat tranh anh sang [^' \
- Tieu chuin nguyen lieu: Cefaclor: dat tieu chuan BP 98; Mannitol: dat tieu c h u i n BP 98;
HPMC: dat tieu ehuan USP 25; PVP: dat tieu ehuan USP 25; Magnesi stearate: dat tieu ehuan DDVN II tap 3; Aerosil: dat tieu ehuan USP 24.
S u m m a r y
Formulation development of sustained release 375 mg Cefaclor have been prepared, the step forward must assess the evaluation of its drug release in comparison with the reference dmg.
Eight formulations were compared the drug release with the reference Ceclor® SR tablet of Lilly Suzhou Pharmaceutical Co., Ltd. Formulation 8 showed the
equivalence of drug release percentages with the reference tablet (18.70; 36,40; 96,20 after 30, 60, 240 minutes versus 16,54; 33,87; 92,96; respectively) and fitted to the specification of USP 29. The based standards of this preparation were also constructed.
T a i lieu thiam k h a o
1. Bhamare et al (2006), "Extended release formulation of beta-lactam antibiotics". US. Pat.
0233878.
2. British Pharmacopoeia (2005), pp 369-370 3. Dyp'c dien Viet Nam 3, (2002), NXB Y Hoc, PL-8.3 4. Handbook of Pharmaceutical excipients (1994)- Second edition, pp. 362-366
5. Hoang Minh Chau, Tryong Van Tu§n (2000).
Dang thuoc co tac dung keo dai va dang phong thich CO kiem soat, tai lieu giang day sau dai hoc Dai hoc Y Dyo'cTP. HCM, tr 1-22
6. Jain kumar et al (2006), "Extended release matrix tablet'. US. Pat. 0159752
7. Le Quan Nghiem (2006-2007). Cac he thing tri lieu thay doi su phdng thich. tai lieu giang Oai hoc Y DyocTP. HCM.tr. 1-3
Khao sat moi lien quan nhan qua trong cong thu'c vien nen ra nhanh chira loratadin 10 mg
Dat van de
Trong mdi cdng thye bao e h i , ngoai dyge chat cdn cd nhiiu thanh p h i n ta d y g e khae nhau. Tinh ehit eua san pham khdng nhiJng tuy thupc vao ban chat vi ham lygng cua nguyen lieu ma cdn bj anh hydng bdi cac d i i u kien san xuit. Khao sat anh hydng giya cac thanh phan trong cdng thye len tinh chat san pham la t i i n d i giup dinh hydng trydc khi t i i n hanh thiit k i va toi y u hoa cdng thCre thuoe. Do dd, viee khao sat m i i lien quan nhan qua giya cac y i u td la mdt viec lam c i n thiit. Trong bai bao nay, md hinh thye nghiem dyge SLP dung vao ehpn lya cac bien so ddc lap trong edng thyc vien nen ra nhanh chya loratadin d i thiit ke cac edng thCre,
Nguyen Thuy Viet Phu'O'ng, Le Quan Nghiem, Dang Van Giap
Khoa Dugc, trudng dgi hgc Y dugc Tp. HCMlam du' lieu eho p h i n mem FormRules nghien CLPU lien quan nhan qua.
Nguyen lieu va phu'O'ng phap
Nguyen lieu
Loratadin (Phap), natri starch glyeolat (Trung Quic), erosearmellose (Trung Q u i c ) , avicel (Dai Loan), lactose DC (DLPC) d i u dat tieu chuan USP 26. Aerosil (Trung Quoc) va magnesi stearat (Trung Quic) dat tieu chuan BP 2001.
D i i u c h i vien nen ra nhanh
Vien nen ra nhanh loratadin 10 mg dyge d i i u e h i theo phyang phap dap t h i n g vdi quy trinh nhy sau:
- c a n eac nguy§n lieu trong cdng thCrc va ray qua ed ray 0,5 mm.
TAP CHi DUQC HQC - 9/2009 (SO 401 NAM 49)
11
• Nghien
CLPU- Ky thuat
- Trpn cae nguyen lieu gdm d y g e e h i t loratadin, ta d y g e sieu ra, lactose DC va ta d y g e dap t h i n g theo nguyen t i c d i n g lygng.
- Trpn sau cung: h i n hgp nguyen lieu tren vdi aerosil va magnesi stearat.
- Dap vien: may dap vien quay trdn, k h i i lygng vien 200 mg, dp CLPng 40-60 N.
K i i m nghiem cac c h i tieu dae tru-ng
Vien nen sau khi dieu ehe dyge kiem nghiem eac chl tieu dae tryng cua vien nen ra nhanh la thdi gian ra va thdi gian t h i m y d t eua vien. Cae chl tieu nay dyge SLP dung lam cae bien so phu thude de kiem tra tinh ehit cua san pham trong qua trinh phan tich lien quan nhan qua. Ngoai ra, vien nen ra nhanh cdn dyge kiem tra v i dp cyng, dp mai mdn va dp ddng deu khoi lygng nhy vien nen thydng.
Thai gian ra (giay): Mdi vien dyge dat vao trong ong nghiem 10 ml dydng kinh 1,5 em ed ehija 2 ml nydc cit. Thdi gian (tinh bing giay) de vien ra ra thanh tCpng manh nhd dyge tinh la thdi gian ra.
L i n lygt thyc hien vdi 6 vien va tinh trung binh.
Thai gian tham wot (giay): Dat 5 t d g i i y lpe hinh trdn vdi dydng kinh 9 cm vao trong dTa petri cd dydng kinh 10 cm. Cho vao dTa petri 9 ml dung djch eosin 0,25% ( k h i i lygng/ the tieh).
Can than dat vien loratadin len tren b i mat cua t d giiy. Thdi gian (tinh b i n g giay) de dung djch eosin t h i m len tren b i mat cua vien nen dyge tinh la thdi gian ydt. L i n lygt thyc hien vdi 6 vien va tinh trung binh.
K§t qua va ban luan T h i i t k i m d hinh t h y c nghiem
Thinh phan cdng thirc: Loratadin 10 mg, ta dyge sieu ra A (biin x,), ta dyge sieu ra B (biin X2), ta dyge dap thing E (biin X3), aerosil 1 mg, magnesi stearat 1 mg, lactose DC vCpa du 200 mg.
Md hinh thtrc nghiem: Md hinh vudng La tinh CO 9 cong thyc dyge thiit k i gom 3 y i u t i la lygng ta_dygc A, lygng ta dyge B va lygng ta dyge E vdi mdi y i u t i cd 3 myc, trinh bay nhy sau:
X CM
4 6 8
X
4 130 150 170
i(A)
6 150 170 130
8 170 130 150
X 3 ( E )
DO lieu thiPC nghiem
K i t qua thyc nghiem v i bao c h i va kiem nghiem theo mo hinh t h i i t k i nhy Bang T
1 2 3 4 5 6 7 8 9
X1
4 4 4 6 6 6 8 8 8
X2
4 6 8 4 6 8 4 6 8
X3
130 150 170 150 170 130 170 130 150
yi
20 25 22 23 35 33 31 48 27
yz 43 50 73 45 74 56 66 75 50
Vdi: y, la thdi gian ra (giay) va y2 la thdi gian t h i m y d t (giay) cua cac vien.Nghien ciru lien quan nhan qua
Vdi dCp lieu dau vao tiy Bang 1, k i t qua phan tich lien quan nhan qua d y g e thye hien bdi phin m i m FormRules v3.02 (2004, Intelligensys, Ltd., UK) vdi tuy ehpn Minimum Description Length (MDL). K i t qua cho thay gi&a cac thanh phin cdng thye (ta d y g e A, B va ta d y g e dap t h i n g E) va tinh e h i t san pham (thdi gian ra, thdi gian tham ydt) ed s y lien quan rd ret.
Cac mdi lien quan dinh tinh (xu hwang) Lygng ta d y g e A (xi), B (X2) va E (X3) ed anh hydng d i n g thdi den thdi gian ra (y,) va thdi gian t h i m y d t eua vien (y2) (Hinh 1 va 2).
Hinh 1. Anh hudng cua ti dugc A. B, E tren thdi gian ra ciia vien
Hinh 2. Anh hudng ciia ti dugc A. B. E tren thdi gian lim ucA cua vien
Cac mdi lien quan dinh Iwang (quy luat) Anh hydng eua l y g n g ta d y g e ra A (Xi) va B (X2) tren thdi gian ra y, n h y sau:
12 TAP CHi DUQC HQC - 9/2009 (SO 401 NAM 49)
Nghien
CLFU- Ky thuat
N i u x, t h i p va X2 thap thi y, t h i p Neu Xi t h i p va X2 trung binh thi y, t h i p Neu Xi t h i p va Xj cao thi y, t h i p N i u Xi cao va X2 t h i p thi y, eao N i u Xi eao va X2 trung binh thi yi cao Neu Xi cao vi X2 eao thi y, t h i p
Hinh 2'. Anh hudng ciia ti dugc A vi B tren thdi gian ra cua vien
Anh hydng eua lygng ta dyge A (x,), B (X2) va E (X3) tren thdi gian t h i m y d t y2:
Neu X3 t h i p va Xi t h i p thi y2 t h i p Neu X3 t h i p va Xi eao thi y2 eao N i u X3 trung binh va x, t h i p thi y2 t h i p N i u X3 trung binh va Xi eao thi y2 t h i p N i u X3 eao va x, t h i p thi y2 eao N i u X3 eao va Xi cao thi y2 cao Neu X2 t h i p thi y2 eao
N i u X2 trung binh thi y2 cao Neu X2 cao thi y2 eao
Hinh 4: Anh hudng cua ti dugc A vi B tren thdi gian lim udt cua vien
Hinh 5: Anh huong cua ti dugc A vi E trin thdi gian lim udt cua vien
Hinh 6: Anh hudng cua ti dugc B vi E tren thdi gian lim udt ciia vien
TLP dd cd the thiy, cac ta dyge anh hydng tren tinh chit san pham theo nhiyng m i i lien quan phCre tap. o i l vdi vien nen ra nhanh, mpt yeu e i u dat ra la thdi gian ra eua vien phai t h i p va thdi gian t h i m ydt eua vien eung thip. Do dd, de dat dyge yeu e i u cua vien nen ra nhanh, lygng ta dyge sieu ra A sy dung cang thap cang tit, ta dyge sieu ra B va ta dyge dap thing E thi phai dung hda giya thdi gian ra va thdi gian t h i m y d t vien.
K§t luan
Viee SLP dung p h i n m i m thdng minh FormRules v3 02, cac quy luat nhan qua da dyge thiit lap. Vdi md hinh thye nghiem d vudng la tinh (cd 9 cong thye) vLPa eho phep giam dyge so thi nghiem tuy nhien v i n khao sat dyge anh hydng cua ba y i u to (ba bien dpc lap) trong edng thye len tinh etiit san p h i m , vdi mdi y i u td dyge khao sat d 3 myc. K i t qua cho thay cac ta dyge sieu ra A, B va ta dyge dap thing E deu eo anh hydng tren tinh c h i t san pham eua vien nen ra nhanh chya loratadin 10 mg.
Summary
In various formulations, the effects of ingredient variables on product properties should be discovered scientifically and systematicaly. Finding these mies can help formulators to save both cost and time in formulation design. This paper introduces a new approach - an intelligent software - for discovering the cause-effect relationships existing in fomnulations. applied to the rapidly disintegrating tablets containing loaratin 10 mg.
Tai lieu tham khao
1. Oang Van Giap (2002), Thi§t kg va toi yu hoa cong thyc va quy trinh, Nha xuat ban Y hoc. Tp. Ho Chi Minh, tr.1-97.
2. Vo Thi Minh Hien (2005), Thiet ke va toi yu hoa cong thyc vien nen ra nhanh NaF 0,25 mg, Khoa luan tot nghiep Dugc sT, Dai Hoc Y dyoc Tp.HCM.
3. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N (2004), Formulation Design and Optimization of Mouth Dissolve Tablets of Nimesulide Using Vacuum Drying Technique, AAPS PhamiSciTech 5(3).
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