Harlacher, Cornelius, Galli, Bruno, Schlauersbach, Jonas, Kehrein, Josef, Hanio, Simon, Heidenreich, Christopher, Lenz, Bettina, Sotriffer, Christoph and Meinel, Lorenz (2022) Predicting Bile and Lipid Interaction for Drug Substances. Molecular pharmaceutics, 19 (8). pp. 2868-2876. ISSN 1543-8392; 1543-8384

Abstract

Predicting biopharmaceutical characteristics and food effects for drug substances may substantially leverage rational formulation outcomes. We established a bile and lipid interaction prediction model for new drug substances and further explored the model for the prediction of bile-related food effects. One hundred and forty-one drugs were categorized as bile and/or lipid interacting and noninteracting drugs using 1H nuclear magnetic resonance (NMR) spectroscopy. Quantitative structure-property relationship modeling with molecular descriptors was applied to predict a drug's interaction with bile and/or lipids. Bile interaction, for example, was indicated by two descriptors characterizing polarity and lipophilicity with a high balanced accuracy of 0.8. Furthermore, the predicted bile interaction correlated with a positive food effect. Reliable prediction of drug substance interaction with lipids required four molecular descriptors with a balanced accuracy of 0.7. These described a drug's shape, lipophilicity, aromaticity, and hydrogen bond acceptor capability. In conclusion, reliable models might be found through drug libraries characterized for bile interaction by NMR. Furthermore, there is potential for predicting bile-related positive food effects.

Item Type:	Article
Keywords:	bile, simulated intestinal fluid, quantitative structure−property relationship, nuclear magnetic resonance spectroscopy, food effect
Date Deposited:	03 Sep 2022 00:46
Last Modified:	03 Sep 2022 00:46
URI:	https://oak.novartis.com/id/eprint/46716