星点设计-效应面法优化醋氯芬酸双层渗透泵控释片处方

Optimization of aceclofenac bi-layer osmotic controlled release tablets formulation using central composite design-response surface methodology

目的优化醋氯芬酸双层渗透泵控释片处方。方法以片芯药层中混悬剂聚氧乙烯、促渗剂、包衣液中增塑剂聚乙二醇的用量和包衣膜增重为考察因素,以2、6、12h累积释放量和2～12h累积释放曲线的线性程度作为优化指标,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。结果最优处方组成:混悬剂为197mg,促渗剂为38mg,致孔剂为3.8g,包衣增量质量分数为7.9%。其释放曲线在2-12h零级释放特征显著,12h累计释放量90%,实测值与预测值无明显差异。结论采用星点设计-效应面法得到了醋氯芬酸双层渗透泵控释片的处方优化模型,实现了处方优化。

Objective To prepare and optimize the formulation of aceclofenac controlled release tablets.Method Central composite design-response surface methodology was used to optimize the formulation.Amount of suspending agent,osmotic agent,amount of pore former in the coating solution and coating weight gain were evaluated as the independent variables.Accumulative drug release at 2,6,12 h and linearity of the release curve were evaluated as the dependant variables.Validation of the optimized formulation was also conducted.Result The optimal formulation consisted of 197 mg poly(ethylene oxide)(PEO N-750),38 mg NaCl,3.8 g polyethylene glycol(PEG 4000) and the tablet weight gain for membrane coating was 7.9%(w) of.The drug release profile in 2-12 h exhibited a zero order character.The accumulative drug release at 12 h was 90%.There was no significant difference between measured value and the predicted one.Conclusion A reliable model is established using response surface methodology and formulation of aceclofenac bi-layer osmotic controlled release tablets could be optimized.