Maraviroc in aqueous co-solvent solutions of n-propanol, ethanol, dimethyl sulfoxide and N,N-dimethylformamide: Solubility determination, preferential solvation and solvent effect analysis

Abstract

The liquid–solid equilibrium and solubility of maraviroc in co-solvent mixtures of n-propanol, ethanol, dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) plus water was obtained via the saturation shake-flask technique between 278.15 K and 323.15 K under 101.2 kPa. For the four aqueous co-solvent mixtures investigated, the mole fraction solubility of maraviroc increased with the increase in the temperature and mass fraction of n-propanol, ethanol, DMSO and DMF. The maximum solubility values of maraviroc were observed in the neat co-solvents. The dependence of the maraviroc solubility on the solvent composition and temperature was mathematically correlated by means of the Jouyban-Acree model. The obtained values of relative average deviation (RAD) and root-mean-square deviation (RMSD) were no more than 4.16 × 10−2 and 49.13 × 10−6, respectively. KAT-LSER model was implemented to get quantitative information about solvent effect on the variation of solubility data. The variation in the maraviroc solubility was dependent upon the hydrogen-bond donation and cavity term in n-propanol + water and ethanol + water mixtures; and the cavity term was the dominant term in the (DMSO + water) and (DMF + water) mixtures. Quantitative study was made for the local mole fraction of ethanol (n-propanol, DMSO and DMF) and water around the maraviroc by the Inverse Kirkwood–Buff integrals method applied to the solubility data determined. Maraviroc was preferentially solvated by ethanol or n-propanol for the aqueous co-solvent mixtures of ethanol or n-propanol in intermediate and ethanol/n-propanol-rich compositions. It was conjecturable that maraviroc could act mainly as a Lewis acid in front to the ethanol or n-propanol molecules. However in the {n-propanol (1) + water (2)} mixture with compositions 0 < x1 < 0.20, ethanol (1) + water (2) mixture with compositions 0 < x1 < 0.25 and DMF/DMSO mixtures within entire compositions, maraviroc was preferentially solvated neither by co-solvent (1) nor by water.