Nguyen Duy Thu va Dig Tap chi KHOA HQC & CONG NGH$ 177(01): 2 3 3 - 2 3 7
N G H I A N C t l t l BAO CHE VIEN NEN K t X HOP PARACETAMOL, ASPIMN, CAFEIN
Nguyen Duy Thu-, Nguyen Thu Qu5'nh Trucmg Dal hpc Y Dupc - DM Thdt Nguyen TOMTAT
Hien nay, trSn thi trudng dugc phdm co rdt nhilu bi^t dugc chfta paracetamol vd chl phdm kit hap paracetamol vdi cdc hogt ehdt khde nhu nhom hg sot, giam dau, chong viem, chflng di ftng,.,. d Viet Nam, chua co cfing trinh nghien cuu n^o ket hgp paracetamol, aspirin vd cafein nhSm muc dich tdng hieu qua giam dau, ddc bi?t trong dau do cSng thang va dau nisa dau. Vifin n^n ket hop paracetamol, aspirin, cafein dd dugc nghien cuu b^o che bdng phucmg phap dap thSng. Vien bdo chl d3 dugc ddnh gid anh hudng cua cdc thdnh phin cdng thftc Idi d^c tinh cua vien, kha nang gidi phfing dugc chat tft vien vd dg on djnh. Trong do, loai vd lugng td duac dinh va td dugc rS cfi anh huong nhilu nhat den tinh chat vd kha nang gidi phfing dugc chat cda vien.
Td' khda: paracetamol, aspirin, cafein, viin nen, phdn tdn, kit hgp DATVANDE
Dau nua ddu Id dau nhftc ddu, cd the dau tdng ndng va keo ddi trong nhieu gid hoac tham chi cd ngay. Mac dii nhieu trudng hgp bi chdng dau nfta dau khfing rd nguyen nhan, nhung trong do cd vai trd cua di truyen va yeu to mfii truong [5].
Mgt loat cac logi thufic ddc biet da dugc thiet ke dl dilu tri dau nfta dau. Nhu trong dilu trj cdp tinh cac thuoc giam dau dugc chi dmh trong cac con dau nfta ddu de ngan chgn cac trieu chung da bdt dau. Thufic chong viem phi steroid (NSAIDs) nhu ibuprofen hogc aspirin, cfi thi giup gidm chung dau nfta dau nhg.
Hieu lyc giam dau cua NSAID mgnh han so vdi paracetamol, dac bigt doi vdi nhftng con dau cfi kem theo vifim. Acetaminophen, aspirin, cafein la thuoc kit hgrp gidm dau va ha sdt, hogt dgng bang each ngan chgn cac chat trong ca thi gay dau va viem. Cafein dugc bilt din vdi khd ndng lam tang hieu qua cua nhilu logi thuoc giam dau. Vi vgy, trong mdt sfi thuoc gidm dau cd chua thanh phan caffein vdi lugng phu hgrp [I], [6], [8].
Mgt sfi thudc gidm dau Id su ket hgp cua nhilu thuoc khac nhau giftp gidm con dau nua ddu nghiem trgng, Ngoai ra, cd nhung thuoc phfii hgp gifta paracetamol vd mfit thudc giam dau khac nhdm lam tdng higu Iyc gidm dau
' Tel- 0945 576557
nhu thudc ket hgp cdc butalbital an than vdi aspirin hogc acetaminophen (Butapap, Phrenlin Forte) hogc paracetamol voi codein (Esgic-Plus, Fioricet) ddi khi dugc dung de dilu tri can dau nua ddu. Tuy nhien cfi nguy CO cao Id cac trieu chung dau dau tang trd Igi khi ngung sft dung thudc.
Theo mgt nghien cftu dugc trinh bay tgi Hgi nghi Ian thu 14 cua Hiep hdi Dau ddu Quoc tl, sy kit h^p efta acetaminophen, aspirin va cafein giup giam dau nfta dau ddng ke so vdi gia dugc va thuoc phu hgp bat ke tufii tac, gidi tinh, hoac chung tgc [3], [4],'«[6], [7], [8].
Hien nay, tren thj truong dugc pham cd rat nhilu bigt dugc chfta paracetamol va che phdm kit hgp paracetamol vdi cdc hoat chat khac nhft nhdm ha sdt, giam dau, chdng viem, chong dj ung,... Nhung d Vigt Nam, chua cd cdng trinh nghien cuu ndo co nghien cftu bao chl kit hgp paracetamol, aspirin vd cafein nhdm myc dich tang hieu qua gidm dau, dgc bigt trong dau do cang thdng va dau nfta ddu.
Vi vay, nhdm myc dich nang cao hieu qiia giam dau trong dau nfta dau, chung tdi tien hdnh dl tai "Nghiin ciru bdo chi vien nin kit hgp paracetamol, aspirin, cafein"
NGUYEN LI$U VA PHU'ONG PHAP Nguyen Il^u, thiet bi
- Nguyen liiu: Paracetamol, aspirin, cafein, NaCMC, HPMC E6, PVP K.30, avicel, Na crosscarmelose, lactose, tinh bgt,
233
Nguyen Duy Thu va Dig Tgp chi KHOA HQC & CONG NGHE 177(01): 2 3 3 - 2 3 7 dicalciphosphat (DCP), HCI, N a O H , nude
tinh khiet.
- Thiit bj: Chay coi, may dap vifin tam sai, mdy thft dg ra, may do dg cftng, may do do tran chay, mdy thft hda tan, may do pH, mdy HPLC Hitachi va cac dyng cu thuy tinh.
P h u a n g phap nghien ciru Phirang phdp bdo che
Bdo c h l vien nen vien nen ket hgp paracetamol, aspirin, cafein d qui md phdng thi nghiem bdng phuong phap dap thang nhu sau; Nghiln d u g c ehdt, td dugc, ray qua ray 0,25 mm, trgn 3 dugc chat vdi cac ta d u g c nhu ta dugc dinh khfi (NaCMC, H P M C E6 hodc PVP K30), ta dugc rd (avicel, ), ta dugc dgn (lactose, tinh bgt, DCP), ta d u g c tron (talc, magie stearat). Dgp vien bdng mdy dap vien tam sai, chay bdng, duong kinh 10 mm.
Phuxmg phap ddnh gid
- Dinh lugng paracetamol, aspirin, cafein trong c h l pham: Phuong phap HPLC UV: budc song 245 nm, cgt C I 8 (4,6 mm,250 mm,5 pm), pha dgng; Nudc/methanol/acetic acid (69:28:3), the tich tiem mdu: 20 pi, toe do ddng 1,0 ml/phftt. Thdi gian phan tich 12 phut.
- Danh gia tieu chuan chat lugng vien nen theo quy djnh cua D u g c dien Viet Nam (DDVN) IV: Dg mdi mdn, do ra, do cftng, do dong deu ham lugng, dg dong deu khdi lugng, dg hda tan, ham lugng.
- Thft nghigm hoa tan in vitro: Theo chuyen lugn danh gia dg hoa tan theo D D V N IV d l danh gia muc do va toe do giai phfing dugc chat ti!r che pham bang he thong thu do hda tan, vdi cac thfing so:
Thiit bi: Canh khuay.
Toe dg khuay: 50 ± 2 vdng/phftt.
Mdi trudng hda tan: 900 ml dung dich HCI 0,1 N.
Nhiet dg mfii truong: 37± 0,5''C.
Sau 15, 30, 45 phut, lay 5,0 ml mau, Igc, dinh lugng va tinh k i t qua bang phuong phap HPLC.
- Phan ti'ch so lieu: Phan mem Excel.
KET QUA NGHIEN C U U
Bk ddnh gia dnh hu'dng cua thanh phan trong cfing thftc tdi tinh ch4t cua vien va kha nang giai phfing dugc c h i t tu vien, thdnh phdn cfing thftc he noi dugc lya chgn nhft sau:
Aspirin 200 mg Paracetamol 250 mg Cafein 65 mg Ta dugc dinh Thay ddi Td dugc rd Thay ddi Td dugc dgn Thay ddi Ta dugc tron Tht^ ddi Anh hu-dng ciia ta dirac dinh
Cfi djnh ty lg cdc thdnh phan khac trong cdng thftc, thay dfii logi vd lugng ta dugc dinh N a C M C , H P M C E 6 , PVP K30 d ty le 5%;
7 , 5 % va 10% kig/klg. Vien dugc bao c h l theo p h u a n g phap va danh gia kha nang giai phdng theo phu'ong phap ghi d tren, ket qud dugc trinh bay d bang I va hinh 1.
Bang I. Anh huang cua td duac dinh Cong thu-c 5 % 7,5% 10%
NaCMC CTI C T 2 C T 3 Dgcung(kp) 7.2 8,8 10,6 HPMCE6 CT4 CTS C T 6 Ddci(ng(kp) 7,5 8,9 10,8 PVP K30 CT7 CTS CT9 Do cung (kp) 7,9 9.5 12,3
100%
paracetamol
Thdi gian (phut)
234
Nguyin Duy Thu vd Dtg Tap chf KHOA HOC & CONG NGHE 177(01): 233-237
Thdi gian (phut) Hinh 1. Anh hirang cua la dirge dinh Nhdn xit: Ta d u g c dinh cfi vai trd dgc biet quan trgng trong p h u o n g phap bao c h l vien nen bdng p h u o n g phap dgp thdng. K i t qua nghie cftu cho t h i y : Khi thay d i i logi td dugc
dinh, khd ndng giai phdng dugc ehdt thay doi theo kha nang k i t dinh cua td d u g c dinh. Khi tdng lugng td dugc dinh trong vien (vdi ca ba loai ta dugc dinh), do c u n g cua vien tang, tfic dp giai phdng d u g c ehdt tii vien giam, tuy nhien m u c dp gidm khong gidng nhau (giam it d vien vdi H P M C va N a C M C , giam nhilu d vien vdi PVP K30).
Vien nen sft dyng td dugc dinh N a C M C d ty le 5%. giai phdng d u g c chat nhanh nhat nen dugc lya chgn de tiep tyc nghien cun.
A n h hirong ciia t a diroc r a
Cfi djnh ty Ie cac thdnh phan khac trong cdng thuc, thay dfii logi va ty le ta dugc ra tu 2,5%, 5%, 7,5% so vdi khfii luong vien. Vien dugc bao che theo phuang phdp va danh gia do hda tan vd kha nang ra theo phuang phap ghi d tren, ket qua duac ftinh bay d bang 3 vd hinh 2.
Bang 2. Anh hu&ng cua td dugc rd Cfing thii-c CTIO C T l l CT12 Avicel 5,0% 2,5% 7,5%
Na crosscarmelose 5,0% 7,5% 2,5%
Thoi gian ra (giay) 135 102 164 Nhgn xit: Khi thay dfii loai vd ty lg ta dugc rS kha nang ra va kha nang giai phdng dugc chat tft vien thay ddi. kha nang gidi phdng tdng theo chieu huong tang cua lugng td dugc ra trong vien vdi ca hai log! ta dugc ra, thdi gian ra giam. dac biet tang manh doi vdi khi tang ty Ig td d u g c sieu ra. N h u vgy, kha nang ra vd kha nang giai phfing dugc chat tft vien phu thugc nhieu vao logi va ty le ta dugc ra. Trong do, vien nen C T II cd ty le avicel; Natri crosscarmelose 1:3 gidi phdng dugc chat nhanh nhat va thdi gian ra ngdn. Do vgy, C T 11 dugc lua chgn de tiep tuc cho cac nghien Cliu tiep theo.
Anh hie&ng cua td dirffc dpn
Cd dinh ty lg cac thanh phan khac trong cong thuc vien va ty Ie ta dugc dgn 2 0 % so vdi khoi lugng vien, thay ddi logi ta d u g c dgn tinh bpt, lactose, D C P . Vien dupc bao c h l theo phuong phdp va danh gia phuong phap ghi d tren, ket qua d u g c trinh bay d bang 3.
235
Nguyen Duy Thu vd Dtg Tgp chi KHOA HQC & CONG NGHE 177(01); 23J-237
Anh hufing cua ta dirg-c tron
Cfi djnh ty Ie cdc thdnh phdn khac trong cdng thuc, thay dfii ty le ta dugc tron, Vien dugc bdo che theo phuang phap va danh gid theo phuong phdp ghi d tren, kit qua dupc trinh bay d bang 4.
Bang 4. Anh hudng cda td duac ddn
15 30 Thdi gian (phut)
45 C6ng thii-c Talc (%) Magnesi stearat (%) Dp trtm chay (g/giay)
CT15 2 0,5 9,8
C T I I 1,0 1,5 12,2
CT16 0,5 2,0 10,6
Hinh 2. Anh hudng cua td dirge rd Bang 3. Anh hudng cua id duac ddn
C6ng thiixTinh bOt Lactose
DCP Th6i gian ra (giSy)
C T I 3 20%
105 C T I 4
20%
112 C T l l
20%
102
Nhgn xet: Ket qud nghien cuu cho thay, thdi gian rd cua vifin bdo che chfta ta dugc dgn tan lactose dai han 7-10 gidy so vdi vien bao chl vdi ta dupc don khdng tan DCP va tinh bpt.
Nhung ket qud danh gia do hda tan cho thay, khfing cd sy khac bigt dang kl ve do hda tan khi thay dfii 3 logi ta dugc dpn tren. Do vgy, CO the lya chgn thay thi 3 logi ta dupc ddn trfin trong cong thuc vien, tuy vdy, de thugn lgi cho qua trinh dap thdng, DCP dugc lya chgn cho nghien cun tiep theo.
Ket qud nghien cftn cho thay ta dugc trcm khong dnh hudng nhilu den kha ndng gidi phdng dupc chat tu vien. Khi thay ddi ty Ie td dugc tron, chi dnh hudng den do tron chay cua todn khfii bpt. 6 ty Ie MgSt:talc 1,5:1 b0t cfi dg tron chay tfit nhat, vi vgy dugc lya chpn cho cfing thuc vien nen ket hgp 3 thdnh phan.
Tu kit qua nghien cuu d tren da lua chgn dugc cdng thftc vien nen ket hpp paracetamol, aspirin, cafein nhu sau:
Aspirin 200 mg Paracetamol 250 mg Cafein 65 mg NaCMC 5%
Avicel 2,5%
Na crosscarmelose 7.5%
DCP 20%
Talc 1%
MgSt 1,5%
KET LUAN
Vien nen ket hgp paracetamol, aspirin vd cafein da dugc bao che va danh gid dnh hudng cua cac thanh phdn cdng thftc tdi dgc tinh cua vien, kha ndng giai phdng dugc ehdt tu vien, kha nang rd, do cung. Trong dd, logi va lupng td dugc dinh va ta dupc ra cd anh huong nhieu nhat den tinh chat va khd ndng giai phfing dupc chat cua vien. Ta dugc dpn va ta dugc tron it anh hudng din khd ndng gidi phdng dupc chat tft vien.
TAI L I $ U THAM KHAO 1. Le Dinh Quang, Nguyen Vdn Long (2008),
"NghiSn cftu bao che vien nen gidi phong nhanh chfta paracetamol vd ibuprofen", Tgp chi Duffc /ipc,386,U. 10-13.
2. Bedi et al (2012), "Development and evaluation
of paracetamol taste masked disintegrating tablets
Nguyin Duy Thu vd Dtg Tap chi KHOA HOC & CONG NGHfi 177(01): 2 3 3 - 2 3 7 using polymer coating technique", Inl J. Pharm.
P f e ™ ,4(3), pp. 129-134.
3, Jerome Goldstein M. D. (2006),
"Acetaminophen, Aspirin, and Caffeine in Combination Versus Ibuprofen for Acute Migraine; Results From a Multicenter, Double- Blind, Randomized, Parallel-Group, Single-Dose, Placebo-Controlled Smdy", Headache, 46, pp.
444-453.
4, Goldstein J. et al., (2005), "Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine; Results from the asset trial". Headache, 45(8), pp. 973-982 5, Lipton R. B, (2001), "Migraine diagnosis and treatment: Results trom the American Migraine Study II", Headache, 41(7), pp. 638-645,
6. Migliardi J. iv. et al. (1994), "CafFeine as an analgesic adjuvant in tension headache", Clin.
Pharmacol Ther , 56, pp. 576-86.
7. Rebecca K. Abma (2009), "A Combination of Acetaminophen, Aspirin, and Caffeine Is Effective in Treating Migraine", Neurology Reviews, 17(12), pp.10,
8. Silberstein S. et al. (1999), "Treatment of menstruation-associated migraine with the nonprescription combination of acetaminophen, aspirin, and caffeine: Resuhs from three randomized, placebo controlled studies", Clin.
FAer., 21(3), pp, 475-491.
SUMMARY
STUDY O F P R E P A R A T I O N T A B L E T CONTAINING P A R A C E T A M O L ASPIRIN, C A F E I N E
Nguyen Duy Thu , Nguyen Thu Quynh TNU - Umversity of Medicine and Pharmacy
Nowadays, there ara many dosage forms containing paracetamol and/or combined with other drugs for pain release, inflammation... In ViSt Nam, there were not ever seen a study m preparation that combined paracetamol with aspirin or cafeine for purpose to increase release pain effect, especially in migraine or stress. A tablet containing paracetamol conbined with aspirin and caffeine were prepared by direct press method. These prepared tablets were tested in effects of formulation, its characteristics and released availability, disintegrating ability. The results show that characteristics and released availability were influenced by formulation's components but specially most by binders and disintegrants, and least by fillers and lubricants.
Keywords; paracetamol, aspirin, cafeine, tablet, dtsmgrating, conbination
Ngay nhan bdi: 27/12/2017; Ngdyplidn biin: 03/01/2018; Ngdy duyit ddng: 30/01/2018 'Tel 0945 576557
