Thermodynamic solubility modelling, solvent effect and preferential solvation of naftopidil in aqueous co-solvent solutions of (n-propanol, ethanol, isopropanol and dimethyl sulfoxide)

Abstract

The naftopidil solubility in aqueous co-solvent mixtures of n-propanol, ethanol, isopropanol and dimethyl sulfoxide (DMSO) at temperatures from 278.15 K to 318.15 K was reported. At fixed composition of n-propanol, ethanol, isopropanol or DMSO and temperature, the mole fraction solubility of naftopidil was highest in DMSO (1) + water (2) mixture, and lowest in isopropanol (1) + water (2) mixture. The Jouyban-Acree model and van’t Hoff-Jouyban-Acree model provided well correlation results obtaining relative average deviation lower than 2.85% and root-mean-square deviation lower than 8.89 × 10−4. Furthermore, the method of linear solvation energy relationships was performed with a suitable combination of solvent polarity descriptors to elucidate the nature of intermolecular interactions giving rise to the solubility variation in co-solvent mixtures. Quantitative values for the local mole fraction of n-propanol (ethanol, isopropanol or DMSO) and water around the naftopidil were computed by using the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. Naftopidil was preferentially solvated by water for the four solvent mixtures in water-rich compositions; while in intermediate and co-solvent-rich compositions for n-propanol (isopropanol and ethanol) (1) + water (2) mixtures, naftopidil was preferentially solvated by the co-solvent. The preferential solvation magnitude of naftopidil was highest in isopropanol mixtures than in the other three co-solvent mixtures.