The preferential solvation parameters (delta x(1,3)) of pioglitazone hydrochloride in four binary solvent mixtures of {ethanol (1) + water (2)), {N-methyl pyrrolidone (NMP) (1) + water (2)), {propylene glycol (1) + water (2)] and {N,N-dimethylsulfoxide (DMSO) (1) + water (2)] were derived from their available solubility data by means of 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. The preferential salvation magnitude of pioglitazone hydrochloride by the co-solvent is highest in {ethanol (1) + water (2)) mixtures and lowest in {propylene glycol (1) + water (2)). For the systems of (ethanol + water) and (NMP + water), the values of delta x(1,3) are negative in water-rich mixtures and co-solvent-rich mixtures, but positive in intermediate compositions. However, for the {propylene glycol (1) + water (2)) and {DMSO (1) + water (2)) mixtures with composition 0.20 < x(1) < 1, the delta x(1,3) values are positive indicating that pioglitazone hydrochloride is preferentially solvated by co-solvent. The positive delta x(1,3) values could be explained based on the higher acidic behaviour of pioglitazone hydrochloride molecules interacting with the hydrogen acceptor groups present in co-solvent. (C) 2017 Elsevier Ltd.