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Challenges in Permeability Assessment for Oral Drug Product Development
by
Mirko Koziolek, Patrick Augustijns, Constantin Berger, Rodrigo Cristofoletti, David Dahlgren, Janneke Keemink, Pär Matsson, Fiona McCartney, Marco Metzger, Mario Mezler, Janis Niessen, James E. Polli, Maria Vertzoni, Werner Weitschies and Jennifer Dressman
Cited by 19 | Viewed by 6188
Abstract
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
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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.
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