Selection of Chrysin cocrystals or hydrated salt to enhance its poor dissolution property

Abstract

The three cocrystals and one hydrated salt of chrysin (CHR) with four coformers (4-Piperidone carboxamide (IPM), 4-dimethylaminopyridine (DMAP), caprolactam (CPL), and triethylenediamine (TEDA)) were successfully prepared and structurally characterized using X-ray diffraction analysis, differential scanning calorimetry, and infrared spectroscopy. The Molecular Electrostatic Potential Surface and Hirshfeld analysis were utilized to inform about surface information and hydrogen interactions, the results revealed that the cocrystals and the hydrated salt were formed via distinct hydrogen-bonding sites, which were attributed to differences in their molecular stacking arrangements. The dissolution and moisture resistance experiments proved the superior stability and solubility of the hydrated salt ([CHR]⁻·[IPM]⁺·H₂O) across various media. Notably, the CHR-DMAP cocrystal exhibited enhanced dissolution performance under simulated intestinal conditions, surpassing both the parent CHR and previously reported CHR cocrystals. These findings highlight the promising utility of the CHR-DMAP cocrystal and hydrated salt of CHR for drug development, with their surface properties and packing features together playing a critical role in improving physicochemical properties.