流通池法测定马来酸依那普利片溶出度及对其体内外相关性的考察

Dissolution testing of enalapril maleate tablets with flowing-through cell method and evaluation of in vivo-in vitro correlation

目的:依据马来酸依那普利片人体血药浓度数据,建立与之相关的体外流通池溶出度测定方法,并用此方法考察5厂家马来酸依那普利片的溶出度。方法:选取20名男性健康受试者口服20mg马来酸依那普利片后血药浓度数据,用3P97药代动力学软件进行拟合,选取最适模型计算各时间点吸收分数;采用流通池法测定马来酸依那普利片的体外溶出度,溶出介质为水,流速为4mL·min-1层流流动方式;以体内吸收分数(Fa)对相应时刻的体外累积溶出百分率(Fd)进行回归;用Weibull分布模型对5厂家溶出曲线进行拟合,提取溶出参数并进行统计分析。结果:马来酸依那普利片药代动力学过程符合一室模型,建立的流通池法测定的体外累积溶出量与体内吸收分数具有非常显著相关性,回归方程为Fa=4.338+0.975Fd,r=0.950,(P<0.01)。5厂家之间马来酸依那普利片溶出参数m、t50及td有非常显著性差异(P<0.01)。结论:所建立的马来酸依那普利片流通池测定方法具有良好的体内外相关性,可以区分不同厂家产品的溶出情况并进行质量控制。

Objective：To develop a flow-through cell dissolution method of enalapril maleate tablets according to human plasma concentration and compare the dissolution of enalapril maleate tablets from 5 manufacturers by this method.Methods：The plasma drug concentration of 20 healthy male volunteers after single 20 mg oral dose was disposed by using 3P97 program.The accumulative Absorption percentage of the optimun models was calculated.Dissolution testing of enalapril maleate tablets using flow-through cell method was carried out by flow speed of 4 mL·min^-1 and water as the medium.The linear regressive equation was established between the Absorption percentage in vivo and the accumulative dissolution percentage in vitro of enalapril maleate tablets and the Weibull equation was used to fit the release curve.The main parameters were calculated and analyzed by statistical method.Results：Pharmacokinetics process of enalapril maleate was fitted the one-compartment model,there was a significant correlation between the Absorption percentage in vivo and the accumulative dissolution percentage in vitro,Fa=4.338＋0.975 Fd,r=0.950,（P〈0.01）.Significant difference existed also among the five batches of tablets by different manufacturers.Conclusion：Because of the significant correlation between the in vivo parameters and the in vitro ones,the method can be used to distinguish the dissolution of different manufacturers and to control the quality of those manufacturers.