Drug Polymorphs by Supercritical AntiSolvent Micronization

摘要

Rifampicin, an antibacterial drug, has been used to investigate the influence of Supercritical AntiSolvent (SAS) process on the solid-state properties, crystal habit and polymorphism of pharmaceutical compounds. Dimethyl sulfoxide (DMSO), dichloromethane (DCM), acetone, ethyl alcohol (EtOH), methyl alcohol (MeOH), and ethyl acetate (EtAc) have been employed as liquid solvents, and carbon dioxide has been used as an antisolvent. The effect of the different solvents on the crystal habit has been studied using SEM (Scan Electron Microscopy) images of both processed compounds, the differences in the crystallinity and polymorphism have been analysed by differential scanning calorimetry (DSC). The x-ray diffraction patterns of rifampicin revealed variations of crystallinity and crystal orientations depending upon the solvent used. The effects of SAS process parameters such as temperature and pressure on the precipitated crystals were investigated for the system rifampicin/EtOH. Pressure did not affect the morphology of the precipitated rfampicin, nevertheless varying the temperature to 40°C and 60°C the micronized powder was modified from hydrate to anhydrous. Anyway, the x-ray analysis showed that there was no primary polymorphic modification varying the operating conditions. In all the cases SAS processed crystals show more ordered appearances with clean surfaces compared with the unprocessed particles.