曲美他嗪固体分散体的制备及缓释性能研究

Studies on preparation of trimetazidine solid dispersion and its sustained release performance

目的:制备曲美他嗪固体分散体,使之具有缓释效果。方法:采用溶剂法制备固体分散体,以固体分散体的体外释放度为评价指标,单因素实验考察载体、制备方法、药物载体比例、致孔剂对曲美他嗪固体分散体缓释性能的影响,通过正交设计对处方及工艺进行优化,并对不同处方的固体分散体体外释药进行动力学拟合。应用DSC,XRD,FTIR考察固体分散体中曲美他嗪的存在状态及其与载体间的相互作用。结果:所得优化处方体外释药可持续24 h,药物体外释药行为符合一级动力学方程,药物释放以Fick扩散为主。曲美他嗪以微晶或无定形态存在于固体分散体中。结论:通过以上优化处方和工艺制备的曲美他嗪固体分散体具有良好的缓释效果及工艺重复性。

Objective：To obtain trimetazidine solid dispersion（SD） with sustained release property.Methods：Trimetazidine sustained release SD was prepared by solvent method.Using in vitro release rate as an index,single factor test was employed to investigate the effects of carriers,preparation methods,ratio of drug/carrier,porosity-making agent on the drug release rate,and orthogonal experiment was used to obtain the optimal formula.Release data in vitro was fitted to kinetic equations.FTIR,DSC and XRD were used to study the existing status of trimetazidine in SD and the interaction between trimetazidine and carriers.Results：The drug release from the optimized formula lasted for 24 h,and the release rate in vitro followed first order kinetics.The release of trimetazidine from SD was controlled mainly by Fick diffusion.XRD and DSC results indicated that trimetazidine existed in crystallitic or amorphous form in SD.Conclusion：Trimetazidine SD prepared under the optimal condition has obvious sustained release property and the processing technology has fairly good reproducibility.