Thermodynamic analysis of the solubility of ketoprofen in some propylene glycol + water cosolvent mixtures

By using the van’t Hoff and Gibbs equations the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution, mixing, and solvation for ketoprofen in propylene glycol + water (PG + W) cosolvent mixtures, were evaluated from solubility data determined at several temperatures. The solubility was greater in pure PG and lower in W at all temperatures studied. By means of enthalpy–entropy compensation analysis, non-linear Δ H soln ° vs. Δ G soln ° plot with negative slope from pure water up to 0.50 in mass fraction of PG and positive beyond this PG proportion was obtained. Accordingly to this result, it follows that the driving mechanism for solubility of KTP in water-rich mixtures is the entropy, probably due to water-structure loosing around the drug non-polar moieties by PG, whereas, over 0.50 in mass fraction of PG the driving mechanism is the enthalpy probably due to KTP solvation increase by cosolvent molecules. On the other hand the Jouyban–Acree model was challenged in front to experimental KTP solubility values finding a predictive power within 30% of deviation.