Chrysin Cocrystals: Prediction, Preparation, Characterization, and In Vitro/In Vivo Evaluation.

In this study, crystal engineering was employed to enhance the solubility and druggability of Chrysin (CHR). Four nitrogen heterocyclic compounds, including piperazine (PIP), 4,4'-bipyridine (BIP), imidazole (IMI), and sophoridine (SOP), were investigated using computational screening methodologies. Screening experiments were conducted to validate the computational screening results, and four CHR crystals were successfully prepared, three of which were reported for the first time. The structures of these cocrystals were characterized by using single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD), and thermal analysis. The spatial structure, arrangement, interactions, and associations were analyzed. Additionally, physical stability, apparent solubility, and biological evaluation were performed to assess those cocrystals. Finally, the CHR-SOP cocrystal shows a significant improvement in solubility and dissolution rate, making it a promising candidate for further study.