中文摘要：

目的：制备依托贝特缓释胶囊,并采用星点设计—效应面法对依托贝特缓释胶囊的处方进行优化。方法：采用离心造粒法制备依托贝特母丸,PEG4000与依托贝特的丙酮溶液包增溶层,以丙烯酸树脂水分散体溶液（Eudragit RL30D）包缓释层。考察因素为增溶层与丸心质量比（X1）、增溶层中PEG4000用量（X2）、缓释层增重百分率（X3）,考察指标为4,8和24 h的累积释放度,采用Design-Expert软件建立模型描述自变量及响应值之间的关系,根据模型绘制效应面图和等高线图,通过重叠等高线图确定优化处方并通过实验对拟合结果进行验证。结果：确定依托贝特的制备处方优化参数：增溶层与丸心质量比为0.7～1.2;PEG4000占增溶层比例为3.5%～12.8%;缓释层包衣增重8.0%～13.5%,与多元线性模型相比,二次多项式模型具较高的置信度;二次多项式模型方程表明考察因素和相对应的考察指标之间存在可信的定量关系;优化处方各考察指标的预测值和实际值非常接近。结论：星点设计—效应面法可用于依托贝特缓释胶囊的处方优化,所建模型具有良好的预测能力。

英文摘要：

Objective： Prepare Etofibrate sustained release capsule;To optimize the formulation of Etofibrate sustained release capsule by Central Composite Design-Response Surface Method Ology（CCD-RSM）.Methods： Etofibrate pellets were prepared by centrifugal granulation equipment,then they were coated by solution of PEG4000 and Etofibrate dissolute in Acetone.Aqueous dispersion of Acrylic Resins（Eudragit RL30D）was used for the sustained release layer coating.In the formulation design using CCD-RSM,independent variables were the mass ratio of solubilize layer,the mass ratio of PEG4000 in the solubilize layer,and the weight gain percentage of sustained release layer.The percentage of in vitro cumulative releases at 4 h,8 h and 24 h were dependent variables.Multilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and overlay contour plots in order to select the optimal formulation.Results： The optimized formulation parameter was： weight ratio of solubilize layer was between 0.7-1.2;the mass ratio of PEG4000 in the solubilize layer was between 3.5%-12.8%;the weight gain percentage of sustained release layer was between 8.0%-13.5 %.Quadratic model showed better prediction capability than multilinear model.The quantitative relationships between three factors and three evaluation indexes were characterized.Moreover,in vitro release test of the selected optimal formulation indicated thigh approximation between the observed and estimated values.Conclusion： The CCD-RSM can be applied to optimize the formulation of Etofibrate sustained release capsule and the established model is of satisfactory predictive value.