星点设计-效应面法优化格列吡嗪渗透泵型缓释片处方

Application of Central Composite Design-response Surface Methodology to Optimize the Formulation of Glipizide Extended Release Osmotic Pump Tablets

目的采用星点设计优化格列吡嗪渗透泵型缓释片处方。方法分别以格列吡嗪缓释片16h释放量（Y，）和累积释放量一时间线性相关系数（Y，）为评价指标，考察包衣增重（X1）、助推层中HPMCK4M用量（X2）和包衣液中PEG4000用量（X3）3个因素对格列吡嗪渗透泵型缓释片释放的影响。用多元线性方程和二次多项式分别评价Y1和Y2与3个影响因素之间的关系，根据Y1、Y2对应的最佳数学模型和实验数据描绘效应面，得出最优处方范围，并进行验证。结果3个影响因素与Y1Y2之间存在定量关系。优选的最佳处方范围分别为：包衣增重X1（20．0～21．5）％、助推层中HPMCK4M用量X2（23．0～25．5）％、包衣液中PEG4000用量X3（5．2～5．5）％。选取优化范围内处方进行实验，其释放曲线与市售片拟合良好。结论所建立的模型预测性良好，可用于预测和优化格列吡嗪渗透泵型缓释片的处方。

OBJECTIVE To optimize the formulation of glipizide extended release osmotic pump tablets by using central compos ite design-response surface methodology. METHODS Release of gilipizide of 16 h from extended release tablets （ Yi ） and linear correlation coefficient of cumulative release amount to time （ Y2 ） were used as the evaluation indexes. The effects of three factors, the semipermeable film weight gain （ X1 ）, the proportion of HPMC K4M in the push layer （ X2 ） and the proportion of PEG4000 in solid content of semipermeable film coating （ X3 ） , on the release of glipizide from the osmotic pump tablets were investigated. The relation- ship between the two evaluation indexes and three influencing factors was described by multiple linear equations and quadratic polyno mials. Corresponding response surfaces were drawn according to the mathematical model and the experimental data of Yi and Y2, which were then used to obtain the optimal prescription range. Finially the optimal prescription range was verified. RESULTS Y1 and Y2 had quantitative relationships with the three factors. The optimum prescription was as follows：the range of semipermeable film weight X1 was 20. 0% -21.5% , the range of the proportion of HPMC K4M in the push layer X2 was 23.0% -25.5% , and the range of the proportion of PEG4000 in solid content of semipermeable fihn coating X3 was 5.2% -5.5%. The release curve of the optimized pre- scription was similar with that of commercial tablets. CONCLUSION Central composite design-response surface methodology is sue- eessfully used to optimize the formulation of glipizide extended release osmotic pump tablets with good prediction ability.