Micronization of Gemfibrozil, Lidocaine, Ethosuximide and Tolbutamide by Rapid Expansion Supercritical Technique

The particle sizes of the pharmaceutical substances are important for their bioavailability, which can be improved by size reduction. In this study, Gemfibrozil, Lidocaine, and Ethosuximide were micronized using the rapid expansion of supercritical solution (RESS) technique. It is found that Gemfibrozil were heterogeneous under certain operational conditions of the RESS process. This phenomenon was explained by phase equilibrium theory. Under modified conditions, the dispersible and micronized gemfibrozil particles were successfully obtained. The effects of extraction temperature, extraction pressure, pre-expansion temperature, post-expansion temperature, and nozzle diameter on the size and morphology of the micronized Lidocaine and Ethosuximide which were further investigated. The crystal habit and polymorphism behavior for Ethosuximide were modified after the RESS process. Finally, Tolbutamide was studied which had an extremely low solubility in supercritical carbon dioxide. Solid co-solvent menthol was used for the micronization of Tolbutamide. The solid co-solvent hindered the particle growth and results in Tolbutamide particle with smaller mean size and polymorphism behavior from form I to form II. Evaluation and comparison of dissolution profile for the original and RESS processed pharmaceutical compounds were investigated. Significant enhancement of dissolution rates for all micronized pharmaceutical compounds was observed.