Novel Salt Cocrystal of Chrysin with Berberine: Preparation, Characterization, and Oral Bioavailability

A novel salt cocrystal of chrysin (ChrH) with berberine (BerbOH), [Berb⁺–Chr^–]-2ChrH (1), was prepared. Crystal structure analysis shows one chrysin lost its proton in 7-hydroxyl group and turned into a chrysin anion. Two neutral chrysin molecules interact simultaneously with chrysin anion through charge-assisted strong hydrogen-bonding interactions between phenolic anion and hydroxyl groups of chrysin to give rise to a 1:3 salt cocrystal based on berberine and chrysin. Density functional theoretical calculations indicate that the 1:3 stoichiometry of berberine and chrysin is more stable due to its largest interaction energies. The bioavailability of chrysin in the form of cocrystal 1 in rats is about 1.7 times than that of pure chrysin.