Solid solubility of antilipemic agents and micronization of gemfibrozil in supercritical carbon dioxide

Abstract

The solid solubilities of three antilipemic agents of clofibric acid, fenofibrate and gemfibrozil in supercritical carbon dioxide were measured using a semi-flow apparatus. The experimental data were taken at three isotherms of 308.2, 318.2 and 328.2 K, with pressure range from 10 to 22 MPa. These measured solid solubilities were correlated by the semi-empirical models of Mendez-Santiago-Teja and Chrastil. A solution model was also employed to fit the measured data. The absolute average deviation in solid solubility from semi-empirical models was 3-7%, and that from the solution model was 4-8%. The measured data satisfied the self-consistency test, and the optimally fitted parameters were reported. Gemfibrozil of the above antilipemic agents had high ranking among the best-selling generic drugs. It was then micronized using the rapid expansion of supercritical solution (RESS) method in this study. The particle size of gemfibrozil was micronized from its original 14.3 to 5.8 £gm. It was also demonstrated that the dissolution rate of micronized gemfibrozil in a simulated intestinal fluid was enhanced by 5.5 times compared to that of the original compound. ? 2010 Elsevier B.V. All rights reserved.