星点设计-效应面法优化尼美舒利双层渗透泵片处方

Optimization of nimesulide bi-layer osmotic pump tablets formulation using response-surface methodology

目的制备大剂量难溶性药物尼美舒利双层渗透泵片,并考察其处方因素和体外释放行为,优化尼美舒利双层渗透泵的处方。方法以12 h药物累积释放量、释放曲线的线性为考察指标,以含药层聚氧乙烯量、包衣膜中致孔剂量、包衣增质量,为考察的主要因素,采用星点设计-效应面法对尼美舒利渗透泵片处方进行优化,并对优化处方进行验证。结果成功找到了最优释药区域,优化处方为：含药层聚氧乙烯220.27 mg,致孔剂用量质量分数为19.27%,包衣增质量6.81%。自制渗透泵与预测值基本一致,2~12 h内药物呈零级释放特征。结论星点设计-效应面法成功建立了处方优化模型,实现了尼美舒利双层渗透泵的处方筛选。

Objective To study the preparation and drug release of nimesulide bi-layer osmotic pump tablets,and optimize formulation.Methods Using accumulative drug release and linearity of the release curve as dependent variables,the amount of polyethylene oxide in drug layer,the amount of macrogol and weight gain in coating as independent variables,central composite design-response surface methodology was applied to optimize nimesulide bi-layer osmotic pump tablets formulation.Results The optimization area was successfully found.The optimal formulation was：220.27 mg PEO,19.27%PEG4000 and weight gain in coating was 6.81%.The dissolution profiles of the self-made osmotic pump tablets were similar to the target profile,and had excellent zero-order release characteristics in the time period of 2-12 h（r=0.996 5）.Conclusions A reliable model is established using response surface methodology and formulation of nimesulide bi-layer osmotic pump tablets can be optimized.