Generation and physicochemical characterization of posaconazole cocrystals using Gas Antisolvent (GAS) and Supercritical Solvent (CSS) methods

•Cocrystals of antifungal drug Posaconazole (PSZ) were prepared with 4-Aminobenzoic Acid (4AMB).•The PSZ-4AMB cocrystal was prepared by Gas Antisolvent (GAS) and Cocrystallisation with a Supercritical Solvent (CSS) methods.•The GAS method led to a higher purity cocrystal compared to the CSS method.•The GAS and CSS methods produced particle sizes (D50) ranging from 20 to 43 µm and 32–42 µm, respectively. [Display omitted] Posaconazole (PSZ) is a BCS (biopharmaceutical classification system) Class II anti-fungal drug used to treat infections in immunocompromised patients. The work presented herein describes the generation of cocrystals of PSZ with 4-aminobenzoic acid (4AMB) using supercritical CO2 as an antisolvent in GAS (Gas Antisolvent) with acetonitrile, and as a solvent in CSS (Cocrystallization with Supercritical Solvent) methods. Cocrystals of PSZ-4AMB were obtained in a 2:3 stoichiometric ratio for the first time by GAS and CSS methods, with GAS producing higher-purity samples compared to CSS method. The work presented herein investigates the influence of critical processing variables using CO2 solvent and antisolvent crystallization methods with respect to the formation of cocrystals of PSZ-4AMB. A Design of Experiments (DoE) approach was performed to assess the outcome of PSZ-4AMB formation, impacted by processing variables such as pressure, temperature, and stirring rate using GAS and CSS methods. The resulting cocrystalline phase was identified using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The particle morphologies and size distributions were determined using scanning electron microscopy and automated static imaging, respectively.