Equilibrium of monomers, dimers, and polymeric aggregates in the α-aryl-propionic acid-type analgesics naproxen, ketoprofen, and ibuprofen: Comparative study with oxicam-type meloxicam and piroxicam

Hydrophobicity is associated with drug transport across membranes and is expressed as the partition coefficient log P for neutral drugs and the distribution coefficient log D for acidic and basic drugs. The log P and log D predictions are deductively (or with artificial intelligence) estimated as the sum of the partial contributions of the scaffold and substituents of a single molecule and are used widely and affirmatively. However, their predictions have not always been comprehensively accurate beyond scaffold differences. For α-aryl propionic acid and oxicam-type analgesics, the pH profiles and methanol contents dependence on hydrophobicity were examined using reversed-phase HPLC, the conventional flask-shaking method. UV spectroscopy and singular value decomposition (SVD) were used to determine the acid dissociation constants. The dehydration of organic solutes in aqueous solutions by methanol rearranged their dispersion states. Therefore, their fluorescent excitation spectra switched dependently on the fluorophore's concentration, suggesting that α-aryl propionic acid-type analgesics reach equilibrium in monomers, dimers, and polymeric aggregations but the oxicam-type ones cannot achieve dimerization. Their dissolution behaviors are dominated by phenomenological processes, generating a type of dissipative structure that is adaptive to the features of individual solutes. The results of this study suggest that the apparent hydrophobicity of organic solutes is reflected in the dissolved state.