Interaction of Povidone with Aromatic Compounds VI: Use of Partition Coefficients (log Kd) to Correlate with log P Values and Apparent Kd Values to Express the Binding as a Function of ph and pka

Abstract

The binding of neutral aromatic compounds onto povidone was studied. It was found that the binding depends on the lipophilic character of the compound and that a linear free relationship exists between the logarithm of the partition coefficients of the macromolecular pseudo-two-phase–aqueous phase, and the log partition coefficient of n-octanol–water (log P). For the ionized ligand molecules it was shown that the binding could be expressed in terms of the acid dissociation constant of the solute, Ka, and in terms of two partition coefficients, K1=HAPVP/HAwater and K2=A−PVP/A−water for the nondissociated and dissociated forms, respectively, resulting in the apparent partition coefficient Kdapp=(HAPVP + A−PVP)/(HAwater + A−water). An expression was derived, permitting one to determine K1, and K2 from measurable quantities. The apparent partition coefficients (Kdapp) were independent of both drug and povidone concentrations, indicating that the modes of povidone compound interactions were essentially invariant over the ranges of systematic variables studied. The method provides a simple means of evaluating ligand—macromolecule interaction as a function of pH of the solvent and pKa of the ligand.