Biopartitioning Micellar Chromatography-Partition Coefficient Micelle/Water as a Potential Descriptor for Hydrophobicity in Prediction of Oral Drug Absorption

Abstract

Biopartitioning micellar chromatography (BMC), which is useful to mimic the drug partitioning process in biological systems, was used as a method for determination of partition coefficients micelle/water (P m/w ) of a set of structurally diverse drugs. BMC is a chromatographic system consisting of polyoxyethylene (23) lauryl ether (Brij 35) micellar mobile phase prepared in physiological conditions and C18 reversed stationary phase. The retention factors were determined for all selected and studied compounds and a correlation between P m/w and oral drug absorption values were obtained. In order to study the similarity between the BMC system and other natural systems of biomembranes, the retention data on BMC were compared with permeability data obtained in Parallel artificial membrane permeation assays (PAMPA lipid model). Molecular descriptors that are believed to influence transcellular transport and oral drug absorption have been calculated in order to obtain a predictive and reliable model for drug permeability. Results presented in this paper indicate that a proposed descriptor for hydrophobicity P m/w , provided, from a statistical point of view, is a better model than other hydrophobicity descriptors.