中心复合设计法制备盐酸奈福泮微孔渗透泵控释片

Preparation of nefopam hydrochloride controlled porosity osmotic pump by central composite design

目的以盐酸奈福泮为模型药物制备微孔渗透泵,控制其在24 h内维持零级释放,且最终释药量达90%以上。方法采用中心复合设计法优化处方。以24 h累计释药量和释药速率为考察指标对包衣膜PEG-400含量和包衣膜厚度2个自变量进行多元线性回归和二项式拟合,并进行预测分析。结果2个影响因素和2个评价指标之间存在定量关系,优化处方各指标的预测值和目标值接近。结论经中心复合设计优化的盐酸奈福泮微孔渗透泵片能24 h零级释药。

Objective To prepare nefopam hydrochloride controlled porosity osmotic pump with the drug release percentage of 90% at zero-order release for 24 h. Methods The optimal formulation was obtained by central composite design. The effects of membrane factors （ amount of PEG-400, thickness of membrane） on the responses, which included Q24 and Rt, were systemically investigated. The linear model and quadratic model was used to analyze the experimental data. Results The quantitative relationships between the two fac- tors and two evaluation indexes were obtained. The predicted and observed values of optimum formulation were similar. Conclusions Central composite design has been successfully used to optimize the porosity osmotic pump. With this method, the nefopam hydrochloride controlled porosity osmotic pump can deliver drug constantly for 24 h.