目的制备pH依赖-时滞型大黄素结肠定位微丸并对影响其体外释药的包衣处方因素进行研究。方法采用离心造粒包衣机以粉末层积法制备载药微丸,并通过依次包衣时滞内层(Eudragit RL 30D)和pH依赖外层(Eudragit FS 30D)制备pH依赖-时滞型大黄素结肠定位微丸;以体外释放度为评价指标,采用相似因子(f2)法统计分析释药曲线,考察影响大黄素微丸体外释药的处方因素。结果最佳时滞层包衣液处方为:Eudragit RL 30D增重5%,HPMC用量60%,滑石粉用量50%,柠檬酸三乙酯用量15%;最佳pH依赖层包衣液处方为:Eudragit FS 30D增重4.6%,滑石粉用量50%,柠檬酸三乙酯用量5%。体外释放度实验表明,pH依赖-时滞型大黄素结肠定位微丸在人工胃液中2 h和人工肠液中3 h的累积释药率小于10%,人工结肠液7 h内基本释放完全,具有明显的结肠定位释药特性。结论通过调整时滞层及pH依赖层包衣厚度可以制备pH依赖-时滞型大黄素结肠定位微丸。

Objective To prepare pH-based and time-lag type pellets of emodin for colon-specific drug delivery and to investigate the prescription factor of pellets release behavior in vitro. Methods The centrifugal granulation and powder layering techniques were applied to preparing the emodin-loaded pellets. Then pH-based and time-lag type pellets for colon-specific delivery were obtained, with Eudragit RL 30D as inner time-lag layer and Eudragit FS 30D as outer pH-dependent layer, respectively. The release curves were analyzed by simulating factor (f₂) and in vitro emodin release behaviors of coated pellets were investigated. Results The optimum coating liquid formulation of time-lag layer was 5% weight gains of Eudragit RL 30D, 60% pore-forming agent amount of HPMC, 50% anti-plastering aid amount of talcum, and 15% plasticizer amount of triethy citrate (TEC). The optimum coating liquid formulation of pH-dependent layer was 4.6% weight gains of Eudragit FS 30D, 50% anti-plastering aid amount of talcum, and 5% plasticizer amount of TEC. The Results of in vitro release showed that the accumulated release rates of the pH-based and time-lag type pellets of emodin for colon-specific drug delivery were less than 10% in the artificial succus gastricus and intestinal juice, and complete release within 7 h was observed in the artificial colic juice, which indicated the obvious features of colon-specific delivery. Conclusion The pH-based and time-lag type pellets of emodin for colon-specific drug delivery are prepared using time-lag and pH-dependent layers by changing their coating levels.

浙江省自然科学基金杰出青年团队项目(R207722);浙江中医药管理局重点项目(2007ZA001);浙江省大学生科技成果推广项目(67401327)