Oral biopharmaceutics tools: recent progress from partnership through the Pharmaceutical Education and Research with Regulatory Links collaboration

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dc.check.date2022-02-01
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorO'Dwyer, Patrick J.
dc.contributor.authorBox, Karl J.
dc.contributor.authorDressman, Jennifer
dc.contributor.authorGriffin, Brendan T.
dc.contributor.authorHenze, Laura J.
dc.contributor.authorLitou, Chara
dc.contributor.authorPentafragka, Christina
dc.contributor.authorStatelove, Marina
dc.contributor.authorVertzoni, Maria
dc.contributor.authorReppas, Christos
dc.contributor.funderHorizon 2020en
dc.date.accessioned2021-02-16T12:05:30Z
dc.date.available2021-02-16T12:05:30Z
dc.date.issued2021-02-01
dc.date.updated2021-02-12T18:48:28Z
dc.description.abstractObjectives: To summarise key contributions of the Pharmaceutical Education and Research with Regulatory Links (PEARRL) project (2016–2020) to the optimisation of existing and the development of new biopharmaceutics tools for evaluating the in vivo performance of oral drug products during the development of new drugs and at the regulatory level. Key findings: Optimised biopharmaceutics tools: Based on new clinical data, the composition of biorelevant media for simulating the fed state conditions in the stomach was simplified. Strategies on how to incorporate biorelevant in vitro data of bio-enabling drug products into physiologically based pharmacokinetic (PBPK) modelling were proposed. Novel in vitro biopharmaceutics tools: Small-scale two-stage biphasic dissolution and dissolution-permeation setups were developed to facilitate understanding of the supersaturation effects and precipitation risks of orally administered drugs. A porcine fasted state simulated intestinal fluid was developed to improve predictions and interpretation of preclinical results using in vitro dissolution studies. Based on new clinical data, recommendations on the design of in vitro methodologies for evaluating the GI drug transfer process in the fed state were suggested. The optimized design of in vivo studies for investigating food effects: A food effect study protocol in the pig model was established which successfully predicted the food-dependent bioavailability of two model compounds. The effect of simulated infant fed state conditions in healthy adults on the oral absorption of model drugs was evaluated versus the fasted state and the fed state conditions, as defined by regulatory agencies for adults. Using PBPK modelling, the extrapolated fasted and infant fed conditions data appeared to be more useful to describe early drug exposure in infants, while extrapolation of data collected under fed state conditions, as defined by regulators for adults, failed to capture in vivo infant drug absorption. Summary: Substantial progress has been made in developing an advanced suite of biopharmaceutics tools for streamlining drug formulation screening and supporting regulatory applications. These advances in biopharmaceutics were achieved through networking opportunities and research collaborations provided under the H2020 funded PEARRL project.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO’Dwyer, P. J., Box, K. J., Dressman, J., Griffin, B. T., Henze, L. J., Litou, C., Pentafragka, C., Statelova, M., Vertzoni, M. and Reppas, C. (2021) 'Oral biopharmaceutics tools: recent progress from partnership through the Pharmaceutical Education and Research with Regulatory Links collaboration', Journal of Pharmacy and Pharmacology, doi: 10.1093/jpp/rgaa055en
dc.identifier.doi10.1093/jpp/rgaa055en
dc.identifier.eissn2042-7158
dc.identifier.endpage10en
dc.identifier.issn0022-3573
dc.identifier.journaltitleJournal of Pharmacy and Pharmacologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/11068
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/674909/EU/Pharmaceutical Education And Research with Regulatory Links: Innovative drug development strategies and regulatory tools tailored to facilitate earlier access to medicines/PEARRLen
dc.rights© The Author(s) 2020. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Pharmacy and Pharmacology following peer review. The version of record is available online at: https://doi.org/10.1093/jpp/rgaa055en
dc.subjectBiorelevanten
dc.subjectIn vitro testingen
dc.subjectPBPK modellingen
dc.subjectPig modelen
dc.subjectPaediatricsen
dc.subjectBio-enabling drug productsen
dc.subjectFood effecten
dc.titleOral biopharmaceutics tools: recent progress from partnership through the Pharmaceutical Education and Research with Regulatory Links collaborationen
dc.typeArticle (peer-reviewed)en
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