Exploring the impact of surfactant type and digestion: Highly digestible surfactants improve oral bioavailability of nilotinib

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dc.contributor.author Koehl, Niklas J.
dc.contributor.author Holm, René
dc.contributor.author Kuentz, Martin
dc.contributor.author Jannin, Vincent
dc.contributor.author Griffin, Brendan T.
dc.date.accessioned 2020-10-19T09:48:23Z
dc.date.available 2020-10-19T09:48:23Z
dc.date.issued 2020-07-10
dc.identifier.citation Koehl, N. J., Holm, R., Kuentz, M., Jannin, V. and Griffin, B. T. (2020) 'Exploring the impact of surfactant type and digestion: Highly digestible surfactants improve oral bioavailability of nilotinib', Molecular Pharmaceutics, 17(9), pp. 3202-3213. doi: 10.1021/acs.molpharmaceut.0c00305 en
dc.identifier.volume 17 en
dc.identifier.issued 9 en
dc.identifier.startpage 3202 en
dc.identifier.endpage 3213 en
dc.identifier.issn 1543-8384
dc.identifier.uri http://hdl.handle.net/10468/10661
dc.identifier.doi 10.1021/acs.molpharmaceut.0c00305 en
dc.description.abstract The scientific rationale for selection of the surfactant type during oral formulation development requires an in-depth understanding of the interplay between surfactant characteristics and biopharmaceutical factors. Currently, however, there is a lack of comprehensive knowledge of how surfactant properties, such as hydrophilic-lipophilic balance (HLB), digestibility, and fatty acid (FA) chain length, translate into in vivo performance. In the present study, the relationship between surfactant properties, in vitro characteristics, and in vivo bioavailability was systematically evaluated. An in vitro lipolysis model was used to study the digestibility of a variety of nonionic surfactants. Eight surfactants and one surfactant mixture were selected for further analysis using the model poorly water-soluble drug nilotinib. In vitro lipolysis of all nilotinib formulations was performed, followed by an in vivo pharmacokinetic evaluation in rats. The in vitro lipolysis studies showed that medium-chain FA-based surfactants were more readily digested compared to long-chain surfactants. The in vivo study demonstrated that a Tween 20 formulation significantly enhanced the absolute bioavailability of nilotinib up to 5.2-fold relative to an aqueous suspension. In general, surfactants that were highly digestible in vitro tended to display higher bioavailability of nilotinib in vivo. The bioavailability may additionally be related to the FA chain length of digestible surfactants with an improved exposure in the case of medium-chain FA-based surfactants. There was no apparent relationship between the HLB value of surfactants and the in vivo bioavailability of nilotinib. The impact of this study's findings suggests that when designing surfactant-based formulations to enhance oral bioavailability of the poorly water-soluble drug nilotinib, highly digestible, medium chain-based surfactants are preferred. Additionally, for low-permeability drugs such as nilotinib, which is subject to efflux by intestinal P-glycoprotein, the biopharmaceutical effects of surfactants merit further consideration. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher ACS Publications en
dc.rights © 2020, American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, after technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.0c00305 en
dc.subject Digestibility en
dc.subject Lipolysis en
dc.subject Nilotinib en
dc.subject Poorly water-soluble drugs en
dc.subject Surfactants en
dc.subject Suspension en
dc.title Exploring the impact of surfactant type and digestion: Highly digestible surfactants improve oral bioavailability of nilotinib 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.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2021-07-10
dc.date.updated 2020-10-15T10:00:23Z
dc.description.version Accepted Version en
dc.internal.rssid 536907323
dc.contributor.funder Horizon 2020 en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Molecular Pharmaceutics en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress niklas.koehl@ucc.ie 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
dc.identifier.eissn 1543-8392


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