Quantitative Interpretation of In Vivo Buccal Absorption of n-Alkanoic Acids by the Physical Model Approach

Abstract

The human studies of Beckett and Moffat on the buccal absorption of n-alkanoic acids were quantitatively and mechanistically interpreted by the theoretical physical model approach. It is believed that a determination of the incremental partition coefficient for the methylene group in the relevant biophase has been achieved. Exceptionally good agreement of the absorption rate-buffer pH profiles between the experimental results and theory was found. The greater rates of absorption of the higher molecular weight acids in the homologous series at constant buffer pH of the drug solution are attributed entirely to the higher partition coefficients for these acids because their pKa values are essentially identical. However, the rightward shifts of the profiles of the homologous series relative to the dissociation curve are due not only to the increasing lipid solubility but also to the presence of an aqueous diffusion layer on the mucosal side of a biphasic aqueous-lipid barrier. A self-consistent, biophysically meaningful factor of 2.33 for the buccal lipoidal membrane-aqueous incremental partition constant for a methylene group was found. Significantly, this evaluative study probably represents the first example of the rigorous application of the physical model approach to the quantitative and mechanistic interpretation of the in vivoabsorption of drugs.