Solution Thermodynamics and Preferential Solvation of Meloxicam in Propylene Glycol + Water Mixtures

The equilibrium solubilities of the analgesic drug meloxicam (MEL) in propylene glycol + water mixtures were determined at several temperatures from 293.15 to 313.15 K. The Gibbs energy, enthalpy, and entropy of solution and of mixing were obtained from these solubility data. The solubility was maximal in neat propylene glycol and very low in pure water at all temperatures studied. A nonlinear plot of Δ_soln H° versus Δ_soln G° gave a negative slope from pure water up to 0.80 mass fraction of propylene glycol and a positive slope above this composition up to neat propylene glycol, at the mean temperature 303.15 K. Accordingly, the driving mechanism for MEL solubility in the water-rich mixtures was the entropy, probably due to water-structure loss around nonpolar moieties of the drug, while for the propylene glycol-rich mixtures it was the enthalpy, probably due to better solvation of the drug. The preferential solvation of MEL by the components of the solvent was estimated by means of the inverse Kirkwood-Buff integral method, showing rather small preferential solvation of MEL by propylene glycol at all compositions.