Abstract
The preferential solvation parameters (δx1,3) 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 δx1,3 vary non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. The preferential solvation 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 δx1,3 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<x1<1, the δx1,3 values are positive indicating that pioglitazone hydrochloride is preferentially solvated by co-solvent. The positive δx1,3 values could be explained based on the higher acidic behaviour of pioglitazone hydrochloride molecules interacting with the hydrogen acceptor groups present in co-solvent.
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