dc.contributor.author |
Koehl, Niklas J. |
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dc.contributor.author |
Henze, Laura J. |
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dc.contributor.author |
Kuentz, Martin |
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dc.contributor.author |
Holm, René |
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dc.contributor.author |
Griffin, Brendan T. |
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dc.date.accessioned |
2020-07-10T08:46:33Z |
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dc.date.available |
2020-07-10T08:46:33Z |
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dc.date.issued |
2020-06-18 |
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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 |
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dc.identifier.uri |
http://hdl.handle.net/10468/10228 |
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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. |
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dc.format.mimetype |
application/pdf |
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dc.language.iso |
en |
en |
dc.publisher |
MDPI |
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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/). |
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dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
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dc.subject |
Amorphous solubility |
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dc.subject |
Landrace pigs |
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dc.subject |
Lipid suspensions |
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dc.subject |
Lipid-based formulation |
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dc.subject |
SEDDS |
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dc.subject |
Self-emulsifying drug delivery system Super-SNEDDS |
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dc.subject |
Supersaturated lipid-based formulations |
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dc.subject |
Supersaturation |
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dc.subject |
Venetoclax |
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dc.title |
Supersaturated lipid-based formulations to enhance the oral bioavailability of venetoclax |
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dc.type |
Article (peer-reviewed) |
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dc.internal.authorcontactother |
Niklas Koehl, Pharmacology & Therapeutics, University College Cork, Cork, Ireland. +353-21-490-3000 Email: niklas.koehl@ucc.ie |
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dc.internal.availability |
Full text available |
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dc.date.updated |
2020-07-10T08:06:42Z |
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dc.description.version |
Published Version |
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dc.internal.rssid |
521493008 |
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dc.contributor.funder |
Horizon 2020
|
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dc.description.status |
Peer reviewed |
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dc.identifier.journaltitle |
Pharmaceutics |
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dc.internal.copyrightchecked |
Yes |
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dc.internal.licenseacceptance |
Yes |
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dc.internal.IRISemailaddress |
niklas.koehl@ucc.ie |
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dc.internal.IRISemailaddress |
laura.henze@ucc.ie |
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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
|
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