New Insights into Using Lipid Based Suspensions for 'Brick Dust' Molecules: Case Study of Nilotinib
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Authors
Koehl, Niklas
Author (Corporation)
Publication date
22.02.2019
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Type
01A - Journal article
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Parent work
Pharmaceutical Research
Special issue
DOI of the original publication
Series
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Volume
36
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Pages / Duration
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Publisher / Publishing institution
Springer
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Abstract
PurposeLipid suspensions have been shown to be a suitablebio-enabling formulation approach for highly lipophilic or‘grease ball’drug molecules, but studies on‘brick dust’drugsare lacking. This study explored the utility of lipid suspensionsfor enhancing oral bioavailability of the rather hydrophobicdrug nilotinibin vivoin rats.MethodsFour lipid suspensions were developed containinglong chain triglycerides, medium chain triglyceride, longchain monoglycerides and medium chain monoglyceridesandin vivobioavailability was compared to an aqueous suspen-sion. Additionally,in vitrolipolysis and wettability tests wereconducted.ResultsNilotinib lipid suspensions did not show a bioavail-ability increase compared to an aqueous suspension. The bio-availability was lower for triglyceride suspensions, relative toboth monoglyceride and an aqueous suspension. The longchain monoglyceride displayed a significantly higher bioavail-ability relative to triglycerides.In vitrolipolysis results suggestedentrapment of nilotinib crystals within poorly dispersible tri-glycerides, leading to slower nilotinib release and absorption.This was further supported by higher wettability of nilotinibby lipids.ConclusionMonoglycerides improved oral bioavailability ofnilotinib in rats, relative to triglycerides. For‘brick dust’drugsformulated as lipid suspensions, poorly dispersible formula-tions may delay the release of drug crystals from the formula-tion leading to reduced absorption.
Keywords
bio-enabling formulation, brick dust, lipid suspension, lipid based formulation, nilotinib
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ISBN
ISSN
0724-8741
1573-904X
1573-904X
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
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Peer review of the complete publication
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Citation
Koehl, N., & Kuentz, M. (2019). New Insights into Using Lipid Based Suspensions for ‘Brick Dust’ Molecules: Case Study of Nilotinib. Pharmaceutical Research, 36. https://doi.org/10.1007/s11095-019-2590-y