Development and evaluation of a biorelevant medium simulating porcine gastrointestinal fluids

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dc.contributor.authorHenze, Laura J.
dc.contributor.authorKoehl, Niklas J.
dc.contributor.authorJansen, Regina
dc.contributor.authorHolm, René
dc.contributor.authorVertzoni, Maria
dc.contributor.authorWhitfield, Phil D.
dc.contributor.authorGriffin, Brendan T.
dc.contributor.funderHorizon 2020en
dc.date.accessioned2020-10-16T10:56:00Z
dc.date.available2020-10-16T10:56:00Z
dc.date.issued2020-06-21
dc.date.updated2020-10-16T10:47:01Z
dc.description.abstractSimulated human intestinal media, have proved to be a useful biopharmaceutics tool as a dissolution media for predicting in vivo dissolution and pharmacokinetic profile in humans. During drug product development preclinical animal models are also required to assess drug product performance, and there is a need to develop species specific intestinal media to similarly predict in vivo pharmacokinetic profiles in each preclinical model. Pigs, are increasingly being used in preclinical drug development, however to date there is a lack of quantitative information about the composition of porcine gastrointestinal (GI) fluids. As a result, a porcine biorelevant medium has not yet been developed, which is essential to improve interpretation and forecast of preclinical results using biorelevant in vitro dissolution studies. GI fluid samples, were collected from landrace pigs, and characterized. Fasted State Simulated Intestinal Fluid of pigs (FaSSIFp) was developed based on the physiological composition of the GI fluids in terms of pH, buffer capacity, osmolality, surface tension, as well as the bile salt, phospholipid and free fatty acid content. This study demonstrated that FaSSIFp was superior at predicting the solubility of the six model drugs in porcine intestinal fluids (PIF). A markedly high correlation (r2 0.98) was observed between the solubility obtained in PIF and FaSSIFp, whereas poor correlation (r2 0.12) was found for the solubility of the model drugs between human FaSSIF and PIF. This confirms that species specific biorelevant intestinal media are crucial to provide more accurate predictions of pharmacokinetic studies in preclinical models. Additionally, the availability of a species specific intestinal medium offers the potential to improve in vitro-in silico approaches to predict in vivo absorption and to reduce the overall number of animals needed in oral drug product development testing.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHenze, L. J., Koehl, N. J., Jansen, R., Holm, R., Vertzoni, M.,Whitfield, P. D. and Griffin, B. T. (2020) 'Development and evaluation of a biorelevant medium simulating porcine gastrointestinal fluids', European Journal of Pharmaceutics and Biopharmaceutics, 154, pp. 116-126. doi: 10.1016/j.ejpb.2020.06.009en
dc.identifier.doi10.1016/j.ejpb.2020.06.009en
dc.identifier.endpage126en
dc.identifier.issn1873-3441
dc.identifier.issn0939-6411
dc.identifier.journaltitleEuropean Journal of Pharmaceutics and Biopharmaceuticsen
dc.identifier.startpage116en
dc.identifier.urihttps://hdl.handle.net/10468/10660
dc.identifier.volume154en
dc.language.isoenen
dc.publisherElsevier B. V.en
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© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en
dc.subjectBiorelevant mediaen
dc.subjectPigsen
dc.subjectGastrointestinal fluiden
dc.subjectDissolution testen
dc.subjectBile saltsen
dc.subjectPhospholipidsen
dc.subjectFaSSIFen
dc.subjectPre-clinical modelen
dc.subjectAnimal modelen
dc.subjectFaSSIFpen
dc.titleDevelopment and evaluation of a biorelevant medium simulating porcine gastrointestinal fluidsen
dc.typeArticle (peer-reviewed)en
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