星点设计-效应面法优化银杏叶总黄酮双层渗透泵控释片处方  

Optimization of bi-layer osmotic pump controlled release tablets of total flavonoids from Ginkgo Folium by central composite design-response surface methodology

作　　者：李江[1] 杨星钢[1,2] 荆恒攀 薛颖娜 王雨薇[1] 萧伟[2,4] 潘卫三[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]江苏康缘药业股份有限公司,江苏连云港222001 [3]浙江工业大学药学院,浙江杭州310014 [4]中药制药过程新技术国家重点实验室,江苏连云港222001

出　　处：《中草药》2014年第12期1702-1708,共7页Chinese Traditional and Herbal Drugs

基　　金：国家重点基础研究发展计划("973"计划)项目:基于释药动力学的多组分缓控释给药体系的评价方法研究(2012CB724001);中药制药过程新技术国家重点实验室开放基金项目:基于现代给药理论的中药缓控释制剂关键技术应用基础研究(SKL2010Z0301)

摘　　要：目的制备银杏叶总黄酮（TFGF）双层渗透泵控释片,运用星点设计-效应面法优化处方。方法以累积释放率为指标,采用单因素对片芯和衣膜处方进行考察;以包衣液中致孔剂聚乙二醇（PEG）的用量和包衣增重为考察因素,以TFGF双层渗透泵控释片在2、14 h累积释放率和1~12 h释放曲线的复相关系数（R2）作为优化指标,应用星点设计-效应面法筛选最佳处方,并对优化处方进行验证。结果最优处方为包衣增重为7.58%,致孔剂用量为3.41 g,实测值与预测值无显著差异,2 h内无突释;14 h内的累积释放率满足要求;1~12 h内药物呈零级释放。结论采用星点设计-效应面法得到了TFGF双层渗透泵控释片的处方优化模型,实现了处方优化并制备了日服1次的TFGF双层渗透泵控释片。Objective To prepare bi-layer osmotic pump controlled release tablet of total flavonoids from Ginkgo Folium （BOPCRT- TFGF）, and to optimize its formulation by central composite design response surface methodology （CCD RSM）. Methods Single-factor test was desigined by screening the formulations of tablet core and coating film. The independent variables comprised of amount of polyethylene glycol in coating solution and coating weight gain, and the dependent variables included the percentages cumulative release of BOPCRT-TFGF after 2 and 14 h and multiple correlation coefficient of druge release profile in 1--12 h. The formulation was optimized by CCD RSM and the optimized formulation was also verified. Results The optimized formulation was as follows： The tablet weight gain in coating was 7.58%, and PEG 4000 was 3.41 g. There was no significant difference between the measured and the predicted values. The cumulative release of the optimal osmotic pump tablets after 2 h did not appear sudden release, and the cumulative release within 14 h was over 85%. The drug release profile in 1--12 h exhibited a zero order character. Conclusion A reliable model is established using response surface methodology and the formulation of BOPCRT-TFGF could be optimized. The BOPCRT-TFGF for administration once daily is prepared.

关 键 词：银杏叶总黄酮 双层渗透泵控释片 星点设计-效应面法 累积释放率 复相关系数 

分 类 号：R283.6[医药卫生—中药学]