乙基纤维素-Eudragit NE30D 双层膜控盐酸文拉法辛缓释微丸的制备

Preparation of ethyl cellulose-Eudragit?NE30D double-layer controlled venlafaxine hydrochloride sustained-release pellets by fluidized bed

目的研究一种使用乙基纤维素及Eudragit?NE30D包衣的制备盐酸文拉法辛缓释微丸的方法,并对其释放机理进行分析。方法通过挤出滚圆法制备含药丸芯,再通过流化床进行包衣,以体外释放度作为标准考察Eudragit?NE30D包衣增重对药物释放的影响;通过扫描电子显微镜和吸水膨胀、干燥失重实验考察包衣膜性质。结果随着乙基纤维素及Eudragit?NE30D包衣增重的增加,药物释放减慢,当内层乙基纤维素包衣增重为6%,Eudragit?NE30D增重为4%时,自制缓释微丸体外释放行为在4种不同溶出介质中(pH值1.2盐酸溶液、pH值4.5磷酸盐缓冲液、pH值6.8磷酸盐缓冲液和水)与原研一致;电镜图片显示微丸表面光滑圆整,在溶出过程中存在吸水膨胀过程。结论此制备方法简便易行且所得微丸与原研质量一致。药物释放由丸芯骨架结构及双层膜控结构共同控制。

Objective To develop a method of preparing venlafaxine hydrochloride sustained-release pellets using ethyl cellulose and Eudragit?NE30D,and to analyze the release mechanism.Methods The drug-loaded inner core was prepared by extrusion spheronization,and then was coated by fluidized bed.The effect of Eudragit?NE30D on drug release was investigated by in vitro evaluation;Scanning electron microscope,water uptake and dry mass loss studies were used to investigate coating film properties.Results As the weight gain of EC and Eudragit?NE30D increased,the drug release was slowed down.When the weight gain of ethyl-cellulose isolated layer reached 6%and the Eudragit?NE30D achieved 4%,the release behavior of self-made pellets was consistent with commercial product in 4 kinds of different dissolution media(pH 1.2 hydrochloric acid solution,pH 4.5 phosphate buffer,pH 6.8 phosphate buffer and water);Electron micrographs showed that the surface of pellets was smooth and round.And the water swelling process was existed during the dissolution.Conclusion The preparation method is simple and easy,and the obtained pellets are consistent with the commercial product.The drug release is controlled by the inner matrix structure and the double-layer controlled structure.