similarity fit factor f2 | Acta Medica Marisiensis

Development of a Dissolution Method for Modified Release Tablets Containing an Insoluble Active Substance

Kelemen Éva Katalin¹, Kelemen LJ¹, Gyéresi Á², Imre Silvia³, Obreja Mona¹

1 Gedeon Richter Romania S.A., Tîrgu Mureș, Romania
2 Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
3 Department of Analytical Chemistry and Drug Control, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objective: The aim of the present work is to develop a discriminative dissolution method for a practically insoluble pharmaceutical active substance such as indapamide.
Methods: Dissolution testing was performed in compliance with USP, using USP apparatus 2. The proper dissolution medium and the optimal rotation per minutes of the apparatus were optimized. In order to quantify the dissolution of indapamide from modified release tablets, a high liquid chromatographic method was developed and validated.
Results: An HPLC method was developed in order to provide adequate specificity trying several column types and different mobile phases. We selected the proper dissolution medium based on indapamide solubility, we determined the optimal speed of rotation of the dissolution tester for the indapamide in the selected medium, then we proved the discriminating power of the developed dissolution method.
Conclusions: A robust and discriminating HPLC method for analyzing dissolution samples containing indapamide was developed and successfully validated.

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.