Production of quercetin-proline cocrystals by means of supercritical CO2 antisolvent

Gas antisolvent (GAS) processing, based on supercritical CO2, was firstly explored to obtain cocrystals of quercetin/L-proline (QUE/PRO). Cocrystallization is a novel mode to enhance physicochemical properties of poorly bioavailable molecules such as quercetin. QUE/PRO cocrystals were prepared by GAS with ethanol as solvent, and the resulting materials were characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), Raman spectroscopy, scanning electron microscopy (SEM), and Surface area determination (BET method). GAS process provided higher cocrystal yield compared to liquid antisolvent (LAS) processing. The ratio between QUE and PRO was the most relevant processing parameter, affecting the cocrystal yield, purity, particle size, and surface area. The QUE/PRO cocrystals produced by GAS presented better dissolution performance compared to LAS produced cocrystals, providing QUE release at least 1.3-times higher at pH 1.2, and 1.5-times higher at pH 6.8. These results indicate that GAS-processing is a promising approach to produce QUE/PRO cocrystals with improved quercetin's dissolution and bioavailability properties, with potential for diverse applications.