Contact
    Start Publications New Insights into Using Lipid Based Suspensions for "Brick ...
    ←  Publication Finder
    Attension

    New Insights into Using Lipid Based Suspensions for "Brick Dust' Molecules: Case Study of Nilotinib

    Year: 2019

    Journal: Pharm. Res., Volume 36, APR

    Authors: Koehl, Niklas J.; Holm, Rene; Kuentz, Martin; Griffin, Brendan T.

    Organizations: Horizon 2020 Marie Sklodowska-Curie Innovative Training Networks programme [674909]; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI129649] Funding Source: NIH RePORTER

    Keywords: bio-enabling formulation; brick dust; lipid suspension; lipid based formulation; nilotinib

    PurposeLipid 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.MethodsFour 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.ResultsNilotinib 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.ConclusionMonoglycerides 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.
    View publication