The solubility of the poorly soluble medicine febuxostat (FXT) (3) in various {polyethylene glycol 400 (PEG 400) (1) + water (H2O) (2)} mixtures has been examined at 298.2-318.2 K and 101.1 kPa. FXT solubility was measured using an isothermal method and correlated with "van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models". FXT mole fraction solubility was enhanced via an increase in temperature and PEG 400 mass fraction in {(PEG 400 (1) + H2O (2)} mixtures. Neat PEG 400 showed the highest mole fraction solubility of FXT (3.11 × 10-2 at 318.2 K), while neat H2O had the lowest (1.91 × 10-7 at 298.2 K). The overall error value was less than 6.0% for each computational model, indicating good correlations. Based on the positive values of apparent standard enthalpies (46.72-70.30 kJ mol-1) and apparent standard entropies (106.4-118.5 J mol-1 K-1), the dissolution of FXT was "endothermic and entropy-driven" in all {PEG 400 (1) + H2O (2)} mixtures examined. The main mechanism for FXT solvation in {PEG 400 (1) + H2O (2)} mixtures was discovered to be an enthalpy-driven process. In comparison to FXT-H2O, FXT-PEG 400 showed the strongest molecular interactions. In conclusion, these results suggested that PEG 400 has considerable potential for solubilizing a poorly soluble FXT in H2O.
Keywords: dissolution thermodynamics; febuxostat; molecular interactions; solubility; {PEG 400 (1) + water (2)} mixtures.