Best practices in current models mimicking drug permeability in the gastrointestinal tract - an UNGAP review

Joseph P O'Shea*, Patrick Augustijns, Martin Brandl, David J Brayden, Joachim Brouwers, Brendan T Griffin, René Holm, Ann-Christin Jacobsen, Hans Lennernäs, Zahari Vinarov, Caitriona M O'Driscoll

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The absorption of orally administered drug products is a complex, dynamic process, dependant on a range of biopharmaceutical properties; notably the aqueous solubility of a molecule, stability within the gastrointestinal tract (GIT) and permeability. From a regulatory perspective, the concept of high intestinal permeability is intrinsically linked to the fraction of the oral dose absorbed. The relationship between permeability and the extent of absorption means that experimental models of permeability have regularly been used as a surrogate measure to estimate the fraction absorbed. Accurate assessment of a molecule's intestinal permeability is of critical importance during the pharmaceutical development process of oral drug products, and the current review provides a critique of in vivo, in vitro and ex vivo approaches. The usefulness of in silico models to predict drug permeability is also discussed and an overview of solvent systems used in permeability assessments is provided. Studies of drug absorption in humans are an indirect indicator of intestinal permeability, but both in vitro and ex vivo tools provide initial screening approaches and are important tools for assessment of permeability in drug development. Continued refinement of the accuracy of in silico approaches and their validation with human in vivo data will facilitate more efficient characterisation of permeability earlier in the drug development process and will provide useful inputs for integrated, end-to-end absorption modelling.

Original languageEnglish
Article number106098
JournalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Volume170
Pages (from-to)106098
Number of pages35
ISSN0928-0987
DOIs
Publication statusPublished - 1. Mar 2022

Bibliographical note

Copyright © 2021. Published by Elsevier B.V.

Keywords

  • In silico models, oral biopharmaceutics
  • In vitro models
  • In vivo models
  • Intestinal permeability
  • Oral absorption

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