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

Show simple item record Koehl, Niklas J. Holm, René Kuentz, Martin Griffin, Brendan T. 2019-02-18T12:33:43Z 2019-02-18T12:33:43Z 2019-02-22
dc.identifier.citation Koehl, 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-y en
dc.identifier.startpage 1 en
dc.identifier.endpage 13 en
dc.identifier.doi 10.1007/s11095-019-2590-y
dc.description.abstract Purpose: 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Springer en
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: en
dc.subject Lipid suspension en
dc.subject Lipid based formulation en
dc.subject Brick dust en
dc.subject Nilotinib en
dc.subject Bio-enabling formulation en
dc.title New insights into using lipid based suspensions for ‘brick dust’ molecules: case study of Nilotinib en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Niklas J. Koehl, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: en
dc.internal.availability Full text available en Access to this article is restricted until 12 months after publication at the request of the publisher en 2020-02-22
dc.description.version Accepted Version en
dc.internal.rssid 478578990
dc.contributor.funder Horizon 2020 en
dc.contributor.funder H2020 Marie Skłodowska-Curie Actions en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Pharmaceutical Research en
dc.internal.IRISemailaddress en
dc.internal.IRISemailaddress 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

Files in this item

This item appears in the following Collection(s)

Show simple item record

This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement