New insights into using lipid based suspensions for ‘brick dust’ molecules: case study of Nilotinib

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dc.check.date2020-02-22
dc.check.infoAccess to this article is restricted until 12 months after publication at the request of the publisheren
dc.contributor.authorKoehl, Niklas J.
dc.contributor.authorHolm, René
dc.contributor.authorKuentz, Martin
dc.contributor.authorGriffin, Brendan T.
dc.contributor.funderHorizon 2020en
dc.contributor.funderH2020 Marie Skłodowska-Curie Actionsen
dc.date.accessioned2019-02-18T12:33:43Z
dc.date.available2019-02-18T12:33:43Z
dc.date.issued2019-02-22
dc.description.abstractPurpose: Lipid suspensions have been shown to be a suitable bio-enabling formulation approach for highly lipophilic or ‘grease ball’ drug molecules, but studies on ‘brick dust’ drugs are lacking. This study explored the utility of lipid suspensions for enhancing oral bioavailability of the rather hydrophobic drug nilotinib in vivo in rats. Methods: Four lipid suspensions were developed containing long chain triglycerides, medium chain triglyceride, long chain monoglycerides and medium chain monoglycerides and in vivo bioavailability was compared to an aqueous suspension. Additionally, in vitro lipolysis and wettability tests were conducted. Results: Nilotinib lipid suspensions did not show a bioavailability increase compared to an aqueous suspension. The bioavailability was lower for triglyceride suspensions, relative to both monoglyceride and an aqueous suspension. The long chain monoglyceride displayed a significantly higher bioavailability relative to triglycerides. In vitro lipolysis results suggested entrapment of nilotinib crystals within poorly dispersible triglycerides, leading to slower nilotinib release and absorption. This was further supported by higher wettability of nilotinib by lipids. Conclusion: Monoglycerides improved oral bioavailability of nilotinib in rats, relative to triglycerides. For ‘brick dust’ drugs formulated as lipid suspensions, poorly dispersible formulations may delay the release of drug crystals from the formulation leading to reduced absorption.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKoehl, N. J., Holm, R., Kuentz, M. and Griffin, B. T. (2019) 'New Insights into Using Lipid Based Suspensions for ‘Brick Dust’ Molecules: Case Study of Nilotinib', Pharmaceutical Research, 36(4), 56 (13 pp). doi: 10.1007/s11095-019-2590-yen
dc.identifier.doi10.1007/s11095-019-2590-y
dc.identifier.endpage13en
dc.identifier.journaltitlePharmaceutical Researchen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/7512
dc.language.isoenen
dc.publisherSpringeren
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.relation.urihttps://link.springer.com/article/10.1007/s11095-019-2590-y
dc.rights© Springer Science+Business Media, LLC, part of Springer Nature 2019. This is a post-peer-review, pre-copyedit version of an article published in Pharmaceutical Research. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11095-019-2590-yen
dc.subjectLipid suspensionen
dc.subjectLipid based formulationen
dc.subjectBrick dusten
dc.subjectNilotiniben
dc.subjectBio-enabling formulationen
dc.titleNew insights into using lipid based suspensions for ‘brick dust’ molecules: case study of Nilotiniben
dc.typeArticle (peer-reviewed)en
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