Screening for pharmaceutical cocrystals using the supercritical fluid enhanced atomization process

The supercritical fluid enhanced atomization (SEA) process was used to produce cocrystals of six different active pharmaceutical ingredients (APIs): indomethacin, theophylline, caffeine, sulfamethazine, aspirin and carbamazepine. Micrometric cocrystals using the FDA-approved sweetener saccharin (SAC) as a cocrystal former were produced from ethanol solutions using supercritical CO₂ as the atomization enhancing fluid. The corresponding cocrystalline phases were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Particle morphologies and size distributions were analyzed by scanning electron microscopy (SEM) and by aerosizer. The results presented here show the formation of cocrystals of all the APIs selected, evidencing the ability and the potentiality of the SEA technique to generate different pharmaceutical cocrystals. Cocrystal particles produced by SEA had similar mean particle size than those produced by classical grinding methods. Interestingly, a new cocrystal form of theophylline-saccharin (likely with a 1:2 stoichiometry) was obtained by the SEA method that has not been previously reported by traditional screening methods.