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采用中心复合设计优化琥珀酸美托洛尔缓释骨架片

Optimization of sustained release matrix tablet of metoprolol succinate using central composite design.

作者信息

Li Li, Sun Huijuan, Gao Jing, Jiang Tao, Gao Yuan, Zhang Jianjun

机构信息

Department of Pharmacy, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Pak J Pharm Sci. 2013 Sep;26(5):929-37.

Abstract

The present study was performed to optimize the formulation of metoprolol succinate (MS) sustained release tablets using hydroxypropyl methylcellulose (HPMC) and sodium alginate (SA) as the matrix combination. After investigating the effects of various parameters on drug release, a 2-factor, 5-level central composite design was employed, using the amount of HPMC K4M (A) and SA (318 cP) (B) as the independent variables and the drug percentage released at 1h, 4h, 8h, 20h (Q1, Q4, Q8, Q20) as the responses. Response surfaces were established to obtain the matrix ranges and the main factors affecting four responses. In order to validate the optimization study, six confirmatory runs were performed; indicating high predictability of response surface methodology for MS sustained release tablets. Data fitting to Peppas equation indicated that the mechanism of drug release could be diffusion along with erosion. This matrix combination can be used as a good alternative to the commercially pellet technology, which was complicated, time-consuming and energy-intensive.

摘要

本研究旨在以羟丙基甲基纤维素(HPMC)和海藻酸钠(SA)作为基质组合,优化琥珀酸美托洛尔(MS)缓释片的处方。在研究了各种参数对药物释放的影响后,采用二因素五水平中心复合设计,以HPMC K4M的用量(A)和SA(318 cP)的用量(B)作为自变量,以1小时、4小时、8小时、20小时释放的药物百分比(Q1、Q4、Q8、Q20)作为响应值。建立响应面以获得基质范围和影响四个响应值的主要因素。为了验证优化研究,进行了六次验证试验;结果表明响应面法对MS缓释片具有较高的预测性。对Peppas方程的数据拟合表明,药物释放机制可能是扩散与溶蚀同时存在。这种基质组合可以作为商业微丸技术的良好替代方案,后者复杂、耗时且耗能。

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