Dissociation constants of several non-steroidal anti-inflammatory drugs in isopropyl alcohol/water mixtures

The dissociation constants of several non-steroidal anti-inflammatories (diclofenac, ketoprofen, flurbiprofen, naproxen, ibuprofen, carprofen, butibufen and fenbufen) have been determined potentiometrically in a series of isopropyl alcohol/water mixtures. The pKa values have been successfully fitted to a general equation previously derived to explain the variation of the dissociation constant of an acid with solvent composition in binary solvent mixtures. The equation used considers that the two solvents interact to form a mixed structure. The parameters obtained show that all the studied drugs are solvated preferentially by this mixed structure in comparison to the pure solvents. This fact explains the systematic deviations in the aqueous pKa estimated values when the linear extrapolation methods from pKa values obtained in several mixed solvents at different compositions are used.