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The inverse Kirkwood-Buff integrals were used to calculate the preferential solvation parameters of the natural polyphenolic compound chrysin in binary mixtures of ethanol (1) + water (2) and methanol (1) + water (2) as a function of their thermodynamic properties. At temperatures between 298.15 K and 318.15 K, chrysin is extremely sensitive to specific solvation effects; therefore, the negative values ofwere found in the water-rich range of 0 &lt;  x 1 &lt; 0.30 for methanol (1) + water (2) and 0 &lt;  x 1 &lt; 0.25 for ethanol (1) + water (2) which suggested that water (2) preferentially dissolves chrysin (3). In co-solvent-rich regions, the values ofwere positive, and the co-solvents preferentially dissolve chrysin (3). The solvation of drugs in water-rich mixtures is likely to be facilitated by hydrophobic hydration around aromatic rings or groups.

Preferential solvation of 5,7-dihydroxyflavone (chrysin) in aqueous co-solvent mixtures of methanol and ethanol