Preferential solvation of diazepam in some aqueous co-solvent mixtures

The preferential solvation parameters (delta x(1,3)) of diazepam in binary solvent mixtures of {ethanol (1) + water (2)}, {propylene glycol (1) + water (2)), {NMP (1) + water (2)} and {1,4-dioxane (1) + water (2)} at 298.2 K and {tert-butanol (1) + water (2)} at (299.2-313.2) K were derived from their available solubility values by using the inverse Kirkwood-Buff integrals method. The values of delta x(1,3) vary non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. For the former four co-solvent mixtures, the preferential solvation magnitude of diazepam by the co-solvent is highest in {1,4-dioxane (1) + water (2)} mixtures and lowest in {ethanol (1) + water (2)) mixtures. For the former four systems, the values of delta x(1,3) are negative in water-rich mixtures, which indicates that diazepam could act as a Lewis base to establish hydrogen bonds with the proton-donor functional groups of the co-solvents (1) (with the exception of 1,4-dioxane). The same behaviour was also observed for ethanol (1) + water (2) mixtures with co-solvent-rich composition. In the {ethanol (1)+ water (2)} mixtures with composition 0.241 < x(1) < 0.688, {NMP (1) + water (2)} mixtures with composition 0.164 < x(1) < 1.0, {propylene glycol (1) + water (2)} mixtures with composition 0.20 < x(1) < 1.0 and {1,4-dioxane (1) + water (2)} mixtures with composition 0.175 < x(1) < 1.0, diazepam is preferentially solvated by co-solvent. Some differences between the behaviours of diazepam in {tert-butanol (1) + water (2)} mixtures and the other four co-solvent mixtures were found. (C) 2017 Elsevier Ltd.