星点设计-效应面法优化盐酸二甲双胍缓释片处方

Optimization of metformin hydrochloride sustained-release tablets by central composite design/response surface methodology

目的应用星点设计-效应面法优化盐酸二甲双胍缓释片的处方。方法以HPMC K100M的用量和Carbopol 71GNF的用量为考察因素,以1,3,6和10 h的累积释放度为考察指标,采用多元线性回归和多元非线性回归拟合选择合适的模型,根据最佳模型绘制效应面图和等高线图,选择最佳处方并进行验证。采用相似因子对自研片和国外进口片在不同介质中的累积释放度进行比较研究。结果优化处方中HPMC K100M和Carbopol 71GNF的用量分别为片重的8%~15%和10%~13%。最佳处方在各时间点的累积释放度的实测值与预测值的偏差均在6%以内。自研片和国外进口片在pH=4.5、pH=6.8和水中的累积释放度相似性因子f2分别为：76.60、75.58和72.38。结论通过星点设计-效应面法建立的模型可以用于盐酸二甲双胍缓释片处方的优化。

Aim To optimize the formulation of metformin hydrochloride sustained-release tablets by central composite design/response surface methodology（CCD）.Methods The independent variables were the amount of HPMC K100M and Carbopol 71GNF,and the dependent variables were the dissolution of metformin hydrochloride at 1,3,6,10 h.Linear or nonlinear mathematic models were used to estimate the relationship between the independent and the dependent variables.Response surface and 2D-contour map were delineated according to the best-fit mathematic models to select the optimized formulation and assess the observed and predicted values.The release rate of the sustained-release tablets and imported tablets were studied by similarity factor.Results Optimized formulation of metformin hydrochloride sustained-release tablets were proposed to consist of 8%～15% HPMC K100M and 10%～13% Carbopol 71GNF.Bias between the observed and predicted values was within 6%.The f2 for the sustained-release tablets and imported tablets in different dissolution mediums（pH=4.5,pH=6.8 and water）were 76.60,75.58 and 72.38.Conclusion It shows that the established model is suitable for metformin hydrochloride sustained-release tablets.