Preferential solvation of naproxen and piroxicam in ethanol plus water mixtures

The preferential solvation parameters of naproxen (NAP) and piroxicam (PIR) in ethanol (EtOH) + water binary mixtures were obtained from their thermodynamic properties by means of the inverse Kirkwood-Buff integrals method. NAP and PIR are very sensitive to specific solvation effects, so the preferential solvation parameter by EtOH, delta x(1,3), is negative in the water-rich mixtures but positive in all the other compositions for both drugs at temperatures of 293.15, 303.15 and 313.15 K. It is conjecturable that in water-rich mixtures the hydrophobic hydration around the aromatic and methyl groups of the drugs plays a relevant role in the solvation. The higher drugs solvation by EtOH in mixtures of similar solvent proportions and in EtOH-rich mixtures could be due mainly to polarity effects. In these mixtures both drugs would be acting as Lewis acids with the EtOH molecules because this co-solvent is more basic than water.