Equilibrium solubility of 6-methylcoumarin in some (ethanol plus water) mixtures: determination, correlation, thermodynamics and preferential solvation

The solubility of 6-methylcoumarin in water, ethanol and nine aqueous ethanol mixtures was determined from 293.15 to 323.15 K. 6-Methylcoumarin solubility expressed in mole fraction was correlated with some well-known correlation/prediction models. Gibbs energy, enthalpy and entropy, for dissolution and mixing processes, were computed using van't Hoff and Gibbs equations. The plot of enthalpy vs. Gibbs energy of dissolution exhibited negative slopes from water to w(1) = 0.20 and from w(1) = 0.90 to ethanol but positive slopes in the interval 0.20 w(1) w(1) = 0.20 is entropy-driven that could be attributed to water molecules releasing originally bounded as 'icebergs' around the drug-non-polar groups. In mixtures of 0.20 w(1) < 0.90, enthalpy-driving mechanism for drug transfer from more-polar to less-polar systems is observed, probably owing to better solvation by ethanol. Inverse Kirkwood-Buff integrals show that 6-methylcoumarin is preferentially solvated by water in water-rich mixtures but preferentially solvated by ethanol in 0.24 x(1) < 1.00.