乳化-溶媒萃取法制备阿昔洛韦生物黏附缓释微球及其工艺影响因素  

Preparation and Influence Factors of Acyclovir-loaded Bioadhesive Microspheres by Emulsification-Solvent Extraction Method

作　　者：罗文卿 柴妙琳 侯佳朋 胡星 潘俊 

机构地区：[1]智能化递药教育部和全军重点实验室(复旦大学),复旦大学药学院药剂学教研室,上海201203

出　　处：《中国医药工业杂志》2013年第3期242-248,共7页Chinese Journal of Pharmaceuticals

基　　金：国家“重大新药创制”科技重大专项(2009ZX09310-006)

摘　　要：采用乙基纤维素(EC)为骨架材料、卡波姆974P为生物黏附材料、丙酮为分散相溶剂、含Span-80的轻质液体石蜡为连续相,采用乳化-溶媒萃取法制备阿昔洛韦(1)生物黏附缓释微球。考察了1原药粉体的粒径对微球形态、载药量、包封率及体外释放行为的影响。结果表明,采用较小粒径(<50 m)原药可制得包封率较高、突释效应较小的微球。在此基础上进行了工艺放大试验,并用以进行体内外黏附性和大鼠体内药动学研究。与未添加卡波姆的1-EC微球相比,所制生物黏附微球在小鼠及大鼠的胃及小肠黏膜表面具有较好的黏附性,显著延长了药物在胃肠道内的滞留时间。大鼠药动学试验表明,本品与1混悬液相比能显著提高生物利用度。Acyclovir （1） -loaded bioadhesive mierospheres were prepared by emulsification-solvent extraction method with ethylcellulose as matrix, Carbopol 974P NF （Cb） as bioadhesive material, acetone as dispersion phase and light liquid paraffin with Span-80 as continuous phase. The influences of the particle size of bulk drug powder on the morphology, drug loading, encapsulation efficiency and in vitro release of the microspheres were investigated. The results showed that product prepared with smaller particle size （〈50 pan） drug powder possessed the properties of higher encapsulation efficiency and lower initial burst release. Based on this, a scale-up preparation was successfully carried out and then the bioadhesiveness and pharmacokinetics were determined. Compared with the microspheres without Cb, the microspheres with Cb showed better bioadhesive effect and the resident time in gastrointestinal tract of mice and rats was significantly prolonged. In the pharmacokinetic study in rats, the bioadhesive microspheres also indicated an improved bioavailability in comparison with I suspension at the same dose.

关 键 词：阿昔洛韦 乳化-溶媒萃取法 生物黏附微球 工艺放大 药动学 

分 类 号：R944.9[医药卫生—药剂学]