Preferential solvation of rosmarinic acid in binary solvent mixtures of ethanol + water and methanol + water according to the inverse Kirkwood–Buff integrals method

Abstract The preferential solvation parameters ( δx 1,3 ) of rosmarinic acid in binary solvent mixtures of ethanol + water and methanol + water were derived from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals method. δx 1,3 was negative in water-rich mixtures but positive in solvent compositions from 0.20 or 0.24 to 1 in mole fraction of methanol or ethanol, respectively. It was conjecturable that in water-rich mixtures, the hydrophobic hydration around the nonpolar aromatic groups of rosmarinic acid played a relevant role in the solvation. The higher solvation by methanol or ethanol in mixtures of similar co-solvent compositions could be mainly due to polarity effects. The preference of rosmarinic acid in intermediate compositions and in methanol-rich or ethanol-rich mixtures could be explained in terms of the higher acidic behavior of rosmarinic acid molecules interacting with the hydrogen acceptor groups in methanol or ethanol. The calculations were required in the pharmaceutical and chemical industries to save time and money in the optimization of the solubilization and/or crystallization process designs.