磷酸川芎嗪微孔渗透泵游离膜扩散动力学研究及其处方优化

Study on Diffusion Kinetics of Tetramethylpyrazine Phosphate Through Free Coating Film of Controlled Porosity Osmotic Pump Tablets and Formulation Optimization

目的以磷酸川芎嗪为模型,拟合适用于微孔渗透泵控释片的经验公式,用于预测不同包衣膜处方下药物释放速度并优化磷酸川芎嗪微孔渗透泵控释片处方。方法用游离膜扩散动力学方法,研究不同包衣液处方、游离膜厚度、溶液黏度与药物扩散速度的函数关系。用均匀设计优化磷酸川芎嗪微孔渗透泵处方。结果以理论的经典公式为原型,以实验数据为根据拟合出适用于微孔渗透泵控释片的经验公式。用均匀设计软件处理磷酸川芎嗪微孔渗透泵释药数据,得到回归方程和优化处方,F检验显示回归方程显著有效,相关系数超过0.99。结论拟合得到的经验公式能很好的预测药物的释放速度,能为进一步研究提供指导。最优处方药物释放均一性、重现性良好,符合零级释药规律,12 h药物释放90%以上。

OBJECTIVE To deduce a modified empirical formula for predicting the release rate of drugs through different coating formulations of controlled porosity osmotic pump tablets （CPOP） using etramethylpyrazine phosphate （TMPP） as a model drug and to optimize the formulation of TMPP CPOP. METHODS The functions between drug release and coating formulation, film thickness and viscosity were studed by using free film diffusion equipment. Uniform design was adopted to optimize formulation. RESULTS Based on the theoretical formula and actual experimental data, the modified empirical formula which fit for controlled porosity osmotic pump tablets had been deduced. Regression equation and the best formulation were calculated by uniform design software. F test indicated that the regression equation was significant,and the linear correlation coefficient exceeded 0. 99. CONCLUSION The modified empirical formula can accurately predict the drug diffusion rate in different conditions, thus it can provide useful information for filrther study. The cumulative release of the best formulation exceeds 90% at 12 h with good reproducibility and conforms to zero order rate.