Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems
Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems
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DOI：
10.1016/j.ijpharm.2008.12.009
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发表时间：
2009-04-17
影响因子：
5.8
通讯作者：
Zhai, Guangxi
中科院分区：
文献类型：
--
作者：
Cui, Jing;Yu, Bo;Zhai, Guangxi
姜黄素是一种难溶于水的药物，口服生物利用度很低。为改善姜黄素的溶解度和口服吸收，研制了一种新型自微乳化给药系统(SMEDDS)。通过对姜黄素的溶出度考察和配伍试验，筛选出SMEDDS制剂的适宜处方。采用单纯形点阵实验设计优化了姜黄素SMEDDS的处方。SMEDDS的最佳配方为：57.5%的表面活性剂(乳化剂OP：Cremoror EL=1：1)、30.0%的助表面活性剂(PEG400)和12.5%的油(油酸乙酯)。姜黄素(21 mg/g)在SMEDDS中的溶解度显著增加。含SMEDDS的姜黄素在水中稀释后的平均粒径约为21 nm。在4℃下3个月的时间内，SMEDDS的粒径和姜黄素的含量没有明显的变化。体外溶出度研究表明，SMEDDS中95%以上的姜黄素在20min内可在pH 1.2或pH 6.8的缓冲溶液中溶出，而姜黄素粗品在60min内溶出度低于2%。考察了姜黄素SMEDDS的大鼠在体肠吸收特性。结果表明，姜黄素在SMEDDS中的吸收是通过脂膜扩散的被动转移方式实现的。小鼠口服吸收实验结果表明，与其混悬液相比，SMEDDS能显著提高姜黄素的口服吸收。我们的研究表明，开发的SMEDDS制剂具有巨大的潜力，可以替代传统的姜黄素口服制剂。(C)2008爱思唯尔B.V.保留所有权利。
Curcumin is a poorly water-soluble drug and its oral bioavailability is very low. A new self-microemulsifying drug delivery system (SMEDDS) has been successfully developed to improve the solubility and oral absorption of curcumin. Suitable compositions of SMEDDS formulation were screened via solubility studies of curcumin and compatibility tests. The formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. The optimal formulation of SMEDDS was comprised of 57.5% surfactant (emulsifier OP:Cremorphor EL= 1: 1), 30.0% co-surfactant (PEG 400) and 12.5% oil (ethyl oleate). The solubility of curcumin (21 mg/g) significantly increased in SMEDDS. The average particle size of SMEDDS-containing curcumin was about 21 nm when diluted in water. No significant variations in particle size and curcumin content in SMEDDS were observed over a period of 3 months at 4 degrees C. The spherical shape of microemulsion droplet was observed under TEM. The dissolution study in vitro showed that more than 95% of curcumin in SMEDDS could be dissolved in pH 1.2 or pH 6.8 buffer solutions in 20 min, however, less than 2% for crude curcumin in 60 min. The in situ absorption property of curcumin-loaded SMEDDS was evaluated in intestines of rats. The results showed the absorption of curcumin in SMEDDS was via passive transfer by diffusion across the lipid membranes. The results of oral absorption experiment in mice showed that SMEDDS could significantly increase the oral absorption of curcumin compared with its suspension. Our study illustrated that the developed SMEDDS formulation held great potential as a possible alternative to traditional oral formulations of curcumin. (C) 2008 Elsevier B.V. All rights reserved.