Supersaturated lipid-based formulations to enhance the oral bioavailability of venetoclax

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dc.contributor.author Koehl, Niklas J.
dc.contributor.author Henze, Laura J.
dc.contributor.author Kuentz, Martin
dc.contributor.author Holm, René
dc.contributor.author Griffin, Brendan T.
dc.date.accessioned 2020-07-10T08:46:33Z
dc.date.available 2020-07-10T08:46:33Z
dc.date.issued 2020-06-18
dc.identifier.citation Koehl, N. J., Henze, L. J., Kuentz, M., Holm, R. and Griffin, B. T. (2020) 'Supersaturated lipid-based formulations to enhance the oral bioavailability of venetoclax', Pharmaceutics, 12(6), 564 (20pp). doi: 10.3390/pharmaceutics12060564 en
dc.identifier.volume 12 en
dc.identifier.issued 6 en
dc.identifier.startpage 1 en
dc.identifier.endpage 20 en
dc.identifier.issn 1999-4923
dc.identifier.uri http://hdl.handle.net/10468/10228
dc.identifier.doi 10.3390/pharmaceutics12060564 en
dc.description.abstract Increasing numbers of beyond Rule-of-Five drugs are emerging from discovery pipelines, generating a need for bio-enabling formulation approaches, such as lipid-based formulations (LBF), to ensure maximal in vivo exposure. However, many drug candidates display insufficient lipid solubility, leading to dose-loading limitations in LBFs. The aim of this study was to explore the potential of supersaturated LBFs (sLBF) for the beyond Rule-of-Five drug venetoclax. Temperature-induced sLBFs of venetoclax were obtained in olive oil, Captex® 1000, Peceol® and Capmul MCM®, respectively. A Peceol®-based sLBF displayed the highest drug loading and was therefore evaluated further. In vitro lipolysis demonstrated that the Peceol®-based sLBF was able to generate higher venetoclax concentrations in the aqueous phase compared to a Peceol®-based suspension and an aqueous suspension. A subsequent bioavailability study in pigs demonstrated for sLBF a 3.8-fold and 2.1-fold higher bioavailability compared to the drug powder and Peceol®-based suspension, respectively. In conclusion, sLBF is a promising bio-enabling formulation approach to enhance in vivo exposure of beyond Rule-of-Five drugs, such as venetoclax. The in vitro lipolysis results correctly predicted a higher exposure of the sLBF in vivo. The findings of this study are of particular relevance to pre-clinical drug development, where maximum exposure is required. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher MDPI en
dc.rights © 2020, the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Amorphous solubility en
dc.subject Landrace pigs en
dc.subject Lipid suspensions en
dc.subject Lipid-based formulation en
dc.subject SEDDS en
dc.subject Self-emulsifying drug delivery system Super-SNEDDS en
dc.subject Supersaturated lipid-based formulations en
dc.subject Supersaturation en
dc.subject Venetoclax en
dc.title Supersaturated lipid-based formulations to enhance the oral bioavailability of venetoclax en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Niklas Koehl, Pharmacology & Therapeutics, University College Cork, Cork, Ireland. +353-21-490-3000 Email: niklas.koehl@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2020-07-10T08:06:42Z
dc.description.version Published Version en
dc.internal.rssid 521493008
dc.contributor.funder Horizon 2020 en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Pharmaceutics en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress niklas.koehl@ucc.ie en
dc.internal.IRISemailaddress laura.henze@ucc.ie en
dc.identifier.articleid 564 en
dc.relation.project info: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/PEARRL en


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© 2020, the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Except where otherwise noted, this item's license is described as © 2020, the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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