Thermal and morphological characterization of micronized acetylsalicylic acid powders prepared by rapid expansion of a supercritical solution

Abstract

Aim of this work was to investigate the solid-state characteristics of micronized acetylsalicylic acid (ASA), produced by rapid expansion of a supercritical carbon dioxide solution (RESS) and to assess whether a correlation could be found between process parameters and solid-state characteristics. Drug solubility in supercritical CO2 was first assessed under various pressure and temperature conditions. DSC, FT-IR, PXRD, SEM, laser light scattering and HPLC were used to characterise the solid phases produced by the RESS. The obtained particles were crystalline, with spectroscopical and diffractometrical pattern overlapping those of the starting available product. However, a strong reduction of particle size was obtained, linearly correlated to pressure imposed during the RESS process, while temperature did not seem to have a major effect. Similar influence of pressure was observed on the final melting temperature of the micronized ASA. The application of a mathematical model allowed to conclude that the melting temperature depression of RESS-prepared ASA powders can be attributed to the decrease of particle dimension rather than to the formation of different solid phases or impurities.