星点设计-效应面法优化托吡酯缓释微丸处方

Optimization of formulation of topiramate controlled release pellets by central composite design-response surface methodology

目的本研究以乙基纤维素(EC)和聚乙烯吡咯烷酮(PVP-K30)为包衣材料,制备托吡酯缓释微丸,并将星点设计-效应面法应用于处方筛选过程中。方法以微丸在1、4和8 h的释放度作为考察指标,将包衣增重和致孔剂比例作为自变量,采用星点设计-效应面优化法,对缓释包衣处方进行优化。结果星点设计-效应面法确定自变量的最优区域为包衣增重5.67%～6.28%,致孔剂比例26.82%～27.42%,在此区域内任取3点进行验证实验,对比各时间点的累积释放度值,3批自制样品符合理论释药目标。结论星点设计-效应面优化法可用于托吡酯微丸缓释包衣处方的优化,所建模型具有较好的预测能力和实用性。

Objective To prepare controlled release pellets of topiramate with blends of ethylcellulose（EC） and PVP-K30 as controlled coating materials and optimize the coating formulation with central composite design-response surface methodology. Methods Drug release from the coated pellets after 1,4 and 8 h were used as response, and the central composite design-response surface meth- odology based on the single factor tests was applied to optimizing controlled coating formulation, namely, ratio of PVP in controlled coating materials and polymer load（ coating weight gain）. Results Compared with desirable release percentage at certain interval, the accumulation of release percentage of three batches was found to meet the expected target. Conclusion Central composite design-re- sponse surface methodology can be applied to optimizing the coating formulation for topiramate sustained release pellets and the models developed in this study have been proved to be predictable and feasible.