酶控渗透泵型结肠定位微丸的制备及体外释放度考察

Preparation for Colon-specific Pellets Controlled by Enzyme Triggering Osmotic Pump and Its Investigation of the Release in Vitro

关键词:  5-氨基水杨酸  果胶钙  微丸  渗透泵

Key words:  5-amino salicylic acid  calcium pectate  pellet  osmotic pump

摘要:

目的 制备以果胶钙和醋酸纤维素为包衣材料，5-氨基水杨酸(5-ASA)为模型药物的酶触发渗透泵型结肠定位微丸，并考察其体外释药特征及释药机制。方法 采用包衣锅法制备含药丸芯，选用L9(3)4正交实验设计，以体外释放度为评价指标优化包衣液处方及丸芯中渗透剂的用量，并进行体外释药模型拟合。结果 制备5-ASA渗透泵酶触发微丸最佳工艺参数为：包衣增重25%；药物与NaCl(丸芯)比为3∶1；醋酸纤维素与果胶钙(包衣液)用量比为2∶3。所得微丸在人工胃液中2 h，人工小肠液中4 h累计释放率<8%，人工结肠液12 h累计释放率>70%，表明结肠定位性较为突出，且可以在结肠持续释放药物以维持局部药物浓度，进一步研究释药机理表明为零级释放。结论 采用果胶钙与醋酸纤维素为包衣材料制备渗透泵酶触发结肠定位微丸可实现结肠定位作用。

Abstract:

OBJECTIVE To prepare colon-specific pellets controlled by enzyme triggering osmotic pump with coating materials of calcium pectate and cellulose acetate, and with 5-amino salicylic acid(5-ASA) as a model drug, as well as to investigate the characteristics and mechanisms of drug delivery in vitro. METHODS Pan coating was adopted to prepare medicine containing pellets. L₉(3)⁴ orthogonal design was applied to optimize the formulation of coating solution and dosage of penetrant in pellets with evaluation index of release in vitro, while mathematical models of the in vitro drug release was fitted. RESULTS　The optimum process parameters preparing for 5-ASA colon-specific pellets controlled by enzyme triggering osmotic pump was as follows: coating weight gain was 25%, the dosage ratio of 5-ASA to NaCl in pellets was 3∶1, the dosage ratio of cellulose acetate to calcium pectate in coating solution was 2∶3. The cumulative release rate of prepared pellets was lower than 8% in simulated gastric fluid (2 h) and in simulated intestinal fluid (4 h) while over 70% in simulated colonic fluid(12 h). All this showed that the pellets possessed excellent colon-specific performance and maintained local drug concentrations by a sustained release in colon. A further study on the release mechanism demonstrated that the in vitro drug release performance belonged to zero-order release. CONCLUSION Colon-specific pellets controlled by enzyme triggering osmotic pump with coating materials of calcium pectate and cellulose acetate have the function of colon-targeting.