Learning how to use IAM chromatography for predicting permeability

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Giuseppe Ermondi, Maura Vallaro, Giulia Caron
The interest for IAM (Immobilized Artificial Membranes) chromatography in the prediction of drug permeability is increasing. Here we firstly set-up a dataset of 253 molecules including neutral and ionized drugs and few organic compounds for which we either measured or retrieved from the literature IAM.PC.DD2 log Kw^IAM data. Then we applied block relevance (BR) analysis to extract from PLS models the relative contribution of intermolecular forces governing log Kw^IAM and Δlog Kw^IAM (a combined descriptor calculated from log Kw^IAM). Finally, the relationship between log Kw^IAM, Δlog Kw^IAM and passive permeability determined in both PAMPA and MDCK-LE systems was looked for. Models provided the basis for a rational application of IAM chromatography in permeability prediction.

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