索拉非尼自微乳化给药系统的制备及药物动力学研究

doi:10.5246/jcps.2011.02.021

索拉非尼自微乳化给药系统的制备及药物动力学研究

刘亚欧, 范洁明, 王学清^*, 张强

1. 北京大学第一医院药剂科, 北京 100034
2. 北京大学医学部药学院药剂学系, 北京 100191

收稿日期:2010-12-06 修回日期:2011-02-10 出版日期:2011-03-15 发布日期:2011-03-15
通讯作者: 王学清*

Preparation of sorafenib self-microemulsifying drug delivery system and its relative bioavailability in rats

Ya-Ou Liu, Jie-Ming Fan, Xue-Qing Wang^*, Qiang Zhang

1. Department of Pharmacy, the First Hospital of Peking University, Beijing 100034, China
2. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Center, Beijing 100191, China

Received:2010-12-06 Revised:2011-02-10 Online:2011-03-15 Published:2011-03-15
Contact: Xue-Qing Wang*

摘要/Abstract

摘要：

索拉非尼 (Sorafenib) 是一种新型抗肿瘤药物, 但其在水中难溶, 生物利用度低。为了增加索拉非尼的生物利用度, 本研究制备了索拉非尼自微乳化给药系统, 并以大鼠为实验动物测定了该给药系统的口服相对生物利用度。该给药系统以油酸乙酯 (20%, w/w)为油相, 聚氧乙烯蓖麻油 (48%, w/w)为主要乳化剂, 聚乙二醇400 (16%, w/w)和乙醇 (16%, w/w)为助乳化剂, 索拉非尼的终浓度为20 mg/mL。该制剂自微乳化后粒径为20-25 nm。与索拉非尼混悬液相比, 自微乳化给药系统可以显著增加索拉非尼的AUC, Cmax 和MRT, 降低清除率, Tmax没有明显变化。尤其是与口服混悬液相比, 其相对生物利用度提高近25倍, 说明索拉非尼自微乳化给药系统有望开发成为增加其口服吸收的药物制剂。

关键词: 非尼, 自微乳化给药系统, 相对生物利用度

Abstract:

Sorafenib is a novel antitumor drug, which is poorly absorbed in the gastrointestinal tract due to its low solubility in water. To improve the bioavailability of sorafenib, a self-microemulsifying drug delivery system (SMEDDS) formulation of sorafenib was prepared and its relative bioavailability in rats was evaluated. The blank SMEDDS was prepared from a mixture of ethyl oleate (oil phase, 20%, w/w), Cremophol EL (surfactant, 48%, w/w), PEG-400 (co-surfactant, 16%, w/w) and ethanol (co-surfactant, 16%, w/w). Sorafenib was subsequently dissolved in the blank SMEDDS to obtain a sorafenib SMEDDS formulation with a final sorafenib concentration at 20 mg/mL. The particle size of the emulsified sorafenib SMEDDS was about 20-25 nm. Compared with sorafenib suspension, the prepared SMEDDS formulation exhibited no effect on the Tmax, significantly increased the AUC, Cmax and MRT and decreased the drug clearance. Most importantly, the oral bioavailability based on AUC0-72 h increased about 25 times after formulating sorafenib in SMEDDS. We concluded that SMEDDS could be a promising vesicle for the oral delivery of the poorly soluble antitumor drug sorafenib.

Key words: Sorafenib, SMEDDS, Relative bioavailability

中图分类号:

R969.1

Supporting:

Foundation items: The 973 Project (Grant No. 2009CB930300), Scientific and Technological Major Special Project -"Significant Creation of New Drugs" (Grant No. 2009ZX09310-001).
^*Corresponding author. Tel.:/fax: 86-10-82801584

刘亚欧, 范洁明, 王学清^*, 张强. 索拉非尼自微乳化给药系统的制备及药物动力学研究[J]. , DOI: 10.5246/jcps.2011.02.021.

Ya-Ou Liu, Jie-Ming Fan, Xue-Qing Wang^*, Qiang Zhang. Preparation of sorafenib self-microemulsifying drug delivery system and its relative bioavailability in rats [J]. , DOI: 10.5246/jcps.2011.02.021.

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