Logistic Classification Models for pH–Permeability Profile: Predicting Permeability Classes for the Biopharmaceutical Classification System

Permeability is used to describe and evaluate the absorption of drug substances in the human gastrointestinal tract (GIT). Permeability is largely dependent on fluctuating pH that causes the ionization of drug substances and also influences regional absorption in the GIT. Therefore, classification models that characterize permeability at wide ranges of pH were derived in the current study. For this, drug substances were described with six data series that were measured with a parallel artificial membrane permeability assay (PAMPA), including a permeability profile at four pH values (3, 5, 7.4, and 9), and the highest and intrinsic membrane permeability. Logistic regression classification models were developed and compared by using two distinct sets of descriptors: (1) a hydrophobicity descriptor, the logarithm of the octanol–water partition (logPow) or distribution (logD) coefficient and (2) theoretical molecular descriptors. In both cases, models have good classification and descriptive capabilities for ...