Solubility and preferential solvation of flubendazole dissolved in aqueous co-solvent mixtures of 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide and isopropanol

Abstract

The equilibrium solubility of flubendazole in four co-solvent mixtures of dimethyl sulfoxide (DMSO,1) + water (2), N,N-dimethylformamide (DMF,1) + water (2), isopropanol (1) + water (2) and 1,4-dioxane (1) + water (2) at temperature range from (283.15 to 333.15) K was reported. At the same composition of DMSO, DMF, isopropanol or 1,4-dioxane and temperature, the mole fraction solubility of flubendazole was highest in DMSO (1) + water (2) mixtures, and lowest in isopropanol (1) + water (2) mixtures. By using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model, flubendazole solubility was well correlated obtaining RAD lower than 5.08% and RMSD lower than 0.20 × 10−4. Quantitative values for the local mole fraction of DMSO (DMF, isopropanol or 1,4-dioxane) and water around the flubendazole were computed by using the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. Flubendazole was preferentially solvated by water in water-rich compositions; while in intermediate and co-solvent-rich composition for DMF (DMSO, 1,4-dioxane) (1) + water (2) mixtures, flubendazole is preferentially solvated by the co-solvent. While for the isopropanol (1) + water (2) mixture, flubendazole was preferentially solvated by water in water-rich and co-solvent-rich compositions; and preferentially solvated by isopropanol in intermediate compositions. The preferential solvation magnitude of flubendazole was highest in 1,4-dioxane mixtures than in the other three co-solvent mixtures.