星点设计-效应面法优选银杏叶双层渗透泵控释片处方工艺

Optimization of Formulation Process of Ginkgo Folium Bi-layer Osmotic Pump Controlled-release Tablets by Central Composite Design-response Surface Methodology

目的:优选银杏叶双层渗透泵控释片的处方工艺,为改善该制剂的临床用药安全性和有效性提供参考。方法:以总黄酮醇苷的累积释放率为评价指标,通过单因素试验筛选含药层、助推层和包衣液处方,利用f2相似因子法进行相似性判断。选择包衣液中PEG4000用量、包衣增重及助推层PEO用量为自变量,药物释放曲线的相关系数和16 h内累积释放率为因变量,采用星点设计-效应面法优选银杏叶双层渗透泵控释片的处方。结果:最优处方为助推层中聚氧乙烯120 mg,包衣液聚乙二醇4000用量1.5 g,包衣增重11%;16 h内累积释放率>90%。结论:制备的渗透泵控释制剂释放曲线符合要求,线性良好(r=0.996 4)。优选的处方工艺稳定可行,可推广于银杏叶双层渗透泵控释片的工业化生产。

Objective： To optimize formulation of Ginkgo Folium bi-layer osmotic pump controlled- release tablets. Method： With accumulative release rate of total flavonol glycosides as index, single-factor tests were adopted to screen formulations of drug-layer, push-layer and coating solution, drug release behavior was evaluated by similarity factor method. Taking the amount of PEG4000 in coating solution, coating weight and the amount of polyoxyethylene in push-layer as independent variables, linearity of release curve and accumulative drug release in 16 h as dependent variables, central composite design-response surface methodology was applied to optimize formulation. Result： Optimum formula was as follows： polyoxyethylene amount of 120 mg, the amount of PEG4000 of 1.5 g, coating weight of 11% ; accumulative release of total flavonol glycosides in 16 h was above 90%. Conclusion： Release curve of this preparation meets requirements with correlation coefficient of 0. 996 4. This optimized formulation is stable and suitable for industrial production of Ginkgo Folium bi-layer osmotic pump controlled-release tablets.