Solution thermodynamics of indomethacin in propylene glycol + water mixtures

The equilibrium solubilities of the analgesic drug indomethacin (IMC) in propylene glycol + water binary 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 the temperatures studied. A non-linear plot of ΔsolnH° vs. ΔsolnG° with negative slope from pure water up to 0.80 in mass fraction of propylene glycol and positive beyond this composition up to neat propylene glycol was obtained at the mean temperature, 303.15 K. This behavior is similar to those reported in the literature for this drug in 1,4-dioxane + water and ethanol + water mixtures. Accordingly, the driving mechanism for IMC solubility in the water-rich mixtures was the entropy, probably due to water-structure loss around non-polar moieties of the drug and for the propylene glycol-rich mixtures it was the enthalpy, probably due to its better solvation of the drug.

► Indomethacin solubility is greatest in propylene glycol and lowest in water at all temperatures.
► Thermodynamic quantities of solution and mixing were obtained from indomethacin solubility data.
► A non-linear plot of ΔsolnH° vs. ΔsolnG° compensation is found for indomethacin at 303.15 K.