Screening the Dissolution Performance of the Modified Release Tablets Containing Insoluble Active Substance in Different Dissolution Media

Objective: The aim of the present work was to examine a test and a marketed product containing indapamide in different dissolution media: hydrochloric acid, acetate buffer solution, phosphate buffer solution, fasted state simulated intestinal fluid and fed state simulated intestinal fluid.
Methods: Dissolution testing was performed in compliance with USP, using USP apparatus 2. In order to quantify the dissolution of indapamide from modified release tablets, a high liquid chromatographic method was developed.
Results: The dissolution profiles registered in different dissolution media were represented graphically and we calculated the difference factor f1 and the similarity factor f2 between the test and the marketed product’s dissolution profiles obtained in different dissolution media. It can be observed that the dissolution behavior of the test and the marketed product is very similar in hydrochloric acid, phosphate buffer solution, in fasted state simulated intestinal fluid and fed state simulated intestinal fluid, but it is not similar in acetate buffer solution.
Conclusions: In case of poorly soluble active substances, such us indapamide, it is very difficult to develop a dissolution method in order to predict the in vivo behavior. It is necessary to investigate the dissolution profiles not only in the routine dissolution medium, and in three different pH solutions, but in biorelevant media, too.