Thermodynamic solubility modelling, solvent effect and preferential solvation of p-nitrobenzamide in aqueous co-solvent mixtures of dimethyl sulfoxide, ethanol, isopropanol and ethylene glycol

The equilibrium p-nitrobenzamide solubility in mixtures of dimethyl sulfoxide (DMSO, 1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and ethylene glycol (EG, 1) + water (2) was determined with a shake-flask method from (293.15 to 328.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of DMSO (ethanol, isopropanol or EG), the mole fraction solubility of p-nitrobenzamide was greater in (DMSO + water) than in ethanol (1) + water (2), isopropanol (1) + water (2) and ethylene glycol (EG, 1) + water (2) mixtures. X-Ray power diffraction analysis of solid phase showed no polymorphic transformation or solvate formation in experiments. The degree of relative importance of solute-solvent and solvent-solvent interactions on the solubility variation was evaluated by the linear solvation energy relationship analysis of solvent effect. The inverse Kirkwood-Buff integrals was used to study the preferential solvation based on thermodynamic solution properties. The parameters of preferential solvation for ethanol and isopropanol were positive in the ethanol (1) + water (2) and isopropanol (1) + water (2) mixtures in co-solvent-rich and intermediate composition, indicating that p-nitrobenzamide was solvated preferentially by the co-solvent. p-Nitrobenzamide acted mainly as a Lewis acid interacting with proton-acceptor functional groups of the co-solvents. Moreover, the drugs' solubility was represented mathematically via the Jouyban-Acree model attaining the average relative deviations smaller than 2.16%. (C) 2019 Elsevier Ltd.