Challenges in Permeability Assessment for Oral Drug Product Development

Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key param...

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Published inPharmaceutics Vol. 15; no. 10; p. 2397
Main Authors Koziolek, Mirko, Augustijns, Patrick, Berger, Constantin, Cristofoletti, Rodrigo, Dahlgren, David, Keemink, Janneke, Matsson, Pär, McCartney, Fiona, Metzger, Marco, Mezler, Mario, Niessen, Janis, Polli, James E, Vertzoni, Maria, Weitschies, Werner, Dressman, Jennifer
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 28.09.2023
MDPI
Subjects
drug absorption
Drug delivery systems
Drug dosages
Drugs
Fosamprenavir
Gastrointestinal system
in silico
in vitro
in vivo
Medical research
Medicine, Experimental
Oral administration
oral drug delivery
Organic chemicals
Permeability
Pharmaceuticals
Physiology
Product development
Proteolysis
Review
Vehicles
Netherlands
Germany
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Summary:Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development. The various methods used to predict, estimate or measure permeability values, ranging from in silico and in vitro methods all the way to studies in animals and humans, are discussed with regard to their advantages, limitations and applications. A special focus is put on novel techniques such as computational approaches, gut-on-chip models and human tissue-based models, where significant progress has been made in the last few years. In addition, the impact of permeability estimations on PK predictions in PBPK modeling, the degree to which excipients can affect drug permeability in clinical studies and the requirements for colonic drug absorption are addressed.
Bibliography:ObjectType-Article-2
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ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15102397