效应面法优化吲哚美辛自HPMC/果胶/氯化钙骨架片的双相释放

效应面法优化吲哚美辛自HPMC/果胶/氯化钙骨架片的双相释放

吴宝剑, 魏秀莉, 卢懿, 吴伟^*

复旦大学药学院药剂学教研室, 上海 200032

收稿日期:2008-07-21 修回日期:2008-11-10 出版日期:2008-12-15 发布日期:2008-12-15
通讯作者: 吴伟*

Optimization of the biphasic release of indomethacin from HPMC/pectin/calcium chloride matrix tablet by response surface methodology

Bao-Jian Wu, Xiu-Li Wei, Yi Lu, Wei Wu^*

Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China

Received:2008-07-21 Revised:2008-11-10 Online:2008-12-15 Published:2008-12-15
Contact: Wei Wu*

摘要/Abstract

摘要：

考察HPMC/果胶/氯化钙骨架片中两个自变量果胶/氯化钙重量比和骨架总重量对吲哚美辛释放的影响。采用二因素五水平星点设计, 效应面法优化Peppas方程拟合参数n、K和T0.1 (10%释放时间)。自变量对双相释放参数n和K值有显著影响, n、K和T0.1值可用二次多项式拟合, 线性拟合效果不佳。数学模型拟合和效应面结果表明果胶/氯化钙重量比和骨架总重量两个因素间有显著交互作用。在具有较大n和T0.1值和较小K值的优化处方中, 其果胶/氯化钙的比例约为1.0, 骨架总重量处于中间值, 约200 mg。优化处方具有很好的预测性, n、K和T0.1值的预测偏差介于-7.33%和6.26%之间。星点设计可用于优化和预测药物从HPMC/果胶/氯化钙骨架片的释放。

关键词: 药物释放, 药物释放, 药物释放, 优化, 优化, 优化, 效应面, 效应面, 效应面, 吲哚美辛, 吲哚美辛, 吲哚美辛, 果胶, 果胶, 果胶, 骨架, 骨架, 骨架, , ,

Abstract: We studied the effect of two independent variables, the pectin/calcium chloride weight ratio and the overall matrix weight in HPMC/pectin/calcium matrix tablet, on the release of indomethacin. A two-factor 5-level central composite experimental design was employed. Responses of the Peppas correlation parameters n and K and the 10% release time (T0.1) were optimized by response surface methodology. Significant effect of the independent variables on the biphasic release parameters, n and K, was observed. N, K and T0.1 were well fitted with the second-order quadratic equations rather than linear equations. Moreover, the mathematic fitting and the response surfaces showed significant cross-interaction between the pectin/calcium chloride ratio and the overall matrix weight. The optimal formulation with larger n, longer T0.1 and smaller K consisted of medium pectin/calcium chloride ratio around 1.0 and medium matrix weight around 200 mg. Validation studies on the optimal formulations showed good predictability of the n, K and T0.1 values with biases within the range of -7.33% and 6.26%. Our results support that central composite design can be used to optimize drug release from HPMC/pectin/calcium matrix tablet with high predictability.

Key words: Drug release, Drug release, Optimization, Optimization, Response surface, Response surface, Indomethacin, Indomethacin, Pectin, Pectin, Matrix, Matrix, ,

Supporting: Foundation item: Shanghai Municipal Committee of Science and Technology (Grant No. 024319114).
^*Corresponding author. Tel.: 86-21-54237833

吴宝剑, 魏秀莉, 卢懿, 吴伟^*
. 效应面法优化吲哚美辛自HPMC/果胶/氯化钙骨架片的双相释放
[J]. .

Bao-Jian Wu, Xiu-Li Wei, Yi Lu, Wei Wu^*
.

Optimization of the biphasic release of indomethacin from HPMC/pectin/calcium chloride matrix tablet by response surface methodology

[J]. .

参考文献

[1] Alderman, D.A. Int. J. Pharm. Tech. Prod. Mfr. 1984, 5, 1-9.
[2] Li, C.L.; Martini, L.G.; Ford, J.L.; Roberts, M. J. Pharm. Pharmacol. 2005, 57, 533-546.
[3] Siepmann, J.; Peppas, N.A. Adv. Drug Deliv. Rev. 2001, 48, 139-157.
[4] Peppas, N.A. Pharm. Acta Helv. 1985, 60, 110-111.
[5] Ritger, P.L.; Peppas, N.A. J. Controlled. Release. 1987, 5, 23-36.
[6] Ritger, P.L.; Peppas, N.A. J. Controlled. Release. 1987, 5, 37-42.
[7] Colombo, P.; Bettini, R.; Santi, P.; Peppas, N.A. Pharm. Sci. Tech. Today. 2000, 3, 198-204.
[8] Siepmann, J.; Podual, K.; Sriwongjanya, M.; Peppas, N.A.; Bodmeier, R. J. Pharm. Sci. 1999, 88, 65-72.
[9] Higuchi, T. J. Pharm. Sci. 1961, 50, 874-875.
[10] Higuchi, T. J. Pharm. Sci. 1963, 52, 1145-1149.
[11] Korsmeyer, R.W.; Gurny, R.; Doelker, E.; Buri, P.; Peppas, N.A. Int. J. Pharm. 1983, 15, 25-35.
[12] Peppas, N.A.; Brannon-Peppas, L. J. Food Eng. 1994, 22, 189-210.
[13] Alur, H.H.; Beal, J.D.; Pather, S.I.; Mitra, A.K.; Johnston, T.P. J. Pharm. Sci. 1999, 88, 1313-1319.
[14] Ferrero, C.; Muñoz-Ruiz, A.; Jiménez-Castellanos, M.R. Int. J. Pharm. 2000, 202, 21-28.
[15] Munday, D.L.; Cox, P.J. Int. J. Pharm. 2000, 203, 179-192.
[16] Ranga Rao, K.V.; Padmalatha Devi, K.; Buri, P. Drug Dev. Ind. Pharm. 1988, 14, 2299-2320.
[17] Wei, X.; Sun, N.; Wu, B.; Yin, C.; Wu, W. Int. J. Pharm. 2006, 318, 132-138.
[18] Wu, B.; Chen, Z.; Wei, X.; Sun, N.; Lu, Y.; Wu, W. Eur. J. Pharm. Biopharm. 2007, 67, 707-714.
[19] Wu, B.; Deng, D.; Lu, Y.; Wu, W. Eur. J. Pharm. Biopharm. 2008, 69, 294-302.
[20] Wei, X.; Chen, Z.; Lu, Y.; Xu, H.; Chen, G.; Wu, W. J. Appl. Polym. Sci. accepted.
[21] Ji, C.; Xu, X.; Wu, W. J. Drug Target. 2007, 15, 123-131.
[22] Lindenstruth, K.; Müller, B.W. Eur. J. Pharm. Biopharm. 2004, 58, 621-627.
[23] Schiermeier, S.; Schmidt, P.C. Eur. J. Pharm. Sci. 2002, 15, 295-305.
[24] Gil, E.C.; Colarte, A.I.; Bataille, B.; Pedraz, J.L.; Rodríguez, F.; Heinämäki, J. Int. J. Pharm. 2006, 317, 32-39.
[25] Que, L.; Wu, W.; Cheng, X.; Hu, T. Pharm. Dev. Tech. 2006, 11, 295-301.
[26] Sun, N.; Wei, X.; Wu, B.; Chen, J.; Lu, Y.; Wu, W. Powd. Tech. 2008, 182, 72-80.