Solubility of chloroxine in aqueous co-solvent mixtures of N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone and 1,4-dioxane: Determination, solvent effect and preferential solvation analysis

Abstract

The equilibrium solubility of amorphous chloroxine in four co-solvent mixtures of dimethyl sulfoxide (DMSO) (1) + water (2), N,N-dimethylformamide (DMF) (1) + water (2), N-methyl-2-pyrrolidone (NMP) (1) + water (2) and 1,4-dioxane (1) + water (2) is reported. Experiments were performed by using the saturation shake-flask technique over the temperature range from (293.15 to 333.15) K. The maximum solubility was observed in neat DMF (DMSO, NMP or 1,4-dioxane) for the four co-solvent mixtures. By using the Jouyban-Acree model, the chloroxine solubility was well correlated obtaining RAD values lower than 3.64% and RMSD values lower than 8.82 × 10−6. Quantitative values for the local mole fraction of DMSO (DMF, NMP or 1,4-dioxane) and water around the chloroxine were computed by using the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. Chloroxine was preferentially solvated by water for the studied mixtures in water-rich compositions; while within intermediate and co-solvent-rich compositions, chloroxine is preferentially solvated by DMSO (DMF, NMP or 1,4-dioxane) in DMSO (DMF, NMP or 1,4-dioxane) + water mixtures. Moreover, in the light of Kamlet and Taft linear solvation energy relationships model, the co-solvency effect was rationalized, and the relative importance of solvent-solute and solvent-solvent interactions was recognized. It was shown that the change in solvent-solvent interaction energy accounted by cavity term governed the solubility variation of chloroxine in all aqueous mixtures.