吲达帕胺片体外溶出度试验与体内药代动力学的相关性

目的: 考察吲达帕胺片在模拟人体各种生理环境的6种试验条件下体外溶出量与体内药代动力学的相关性,为建立科学合理的吲达帕胺片体外溶出度测定方法提供依据。 方法: 采用模拟人体生理环境的6种试验条件对18批吲达帕胺片进行溶出曲线的测定,并对其相似性进行评价。以进口制剂为参比,选择与其体外溶出行为最为相似和最不相似的2批国内产品为受试制剂,测定18名男性健康受试者单剂量口服吲达帕胺片后全血中吲达帕胺的经时过程,同时对体外溶出量与体内吸收情况的相关性进行考察。 结果: 3种制剂体内吸收分数与6种试验条件下对应时间点体外累积溶出量均具有良好的相关性,其中以桨法50 r·min^-1,pH 4.0醋酸盐缓冲液为溶出介质的试验条件体内外相关性最好。 结论: 吲达帕胺具有良好的体内外相关性,可以用体外相对简单的溶出度测定方法预测药物在体内的吸收过程。

Objective: To study the in vitro-in vivo correlation(IVIVC)of in vitro dissolution and in vivo pharmacokinetics of indapamide tablets under six test conditions mimicking human physiological environment,so as to develop a scientific and reasonable determination method for in vitro dissolution. Methods: The dissolution curves of 18 batches of indapamide tablets were determined under six test conditions,and the similarity of the curves was evaluated.The imported drug was used as a reference preparation,and two groups of domestic products with most similar or the most different dissolution performance were chosen for further in vivo analysis.Indapamide in peripheral blood after single oral dose of indapamide tablets was determined in 18 healthy male volunteers,and the amount of in vitro dissolution and in vivo absorption was simultaneously investigated. Results: A linear regression was observed between the absorption fraction received and the corresponding cumulative dissolution in vitro.The best dissolution was preceded with paddle apparatus as 50 r·min^-1 and using pH 4.0 acetate buffer solution as dissolution medium. Conclusion: The results shows that the IVIVC of indapamide is good.Namely,a relatively simple in vitro dissolution method can be used for the prediction of in vivo absorption process.

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