Dependence of SAS particle morphologies on the ternary phase equilibria

In this work, the precipitation of a model compound (cefonicid) from DMSO by Supercritical Antisolvent (SAS) was performed. Various morphologies; i.e., expanded microparticles, microparticles, and nanoparticles were obtained, varying operating conditions. In order to explain these results, high-pressure vapor–liquid phase equilibria (VLEs) of the binary system DMSO-CO2 and of the ternary system DMSO-CO2-cefonicid were investigated, using a static analytic method. At 313 K and low concentrations, the presence of the solute had a negligible effect on VLEs with respect to the binary system solvent-CO2. At concentrations up to 90 mg/mL (at 313 K) or increasing temperature at 333 K (at 30 mg/mL), a large modification of the VLEs was observed. The changes in phase behavior were successfully correlated to the powder morphologies, considering the position of the SAS operating point with respect to the ternary mixture critical point. The given explanations can be readily extended to other compounds.