Peer-Reviewed Journal Details
Mandatory Fields
Koehl, NJ;Holm, R;Kuentz, M;Griffin, BT
2019
April
Pharmaceutical Research
New Insights into Using Lipid Based Suspensions for "Brick Dust' Molecules: Case Study of Nilotinib
Validated
WOS: 6 ()
Optional Fields
DRUG-DELIVERY SYSTEMS IN-VIVO PERFORMANCE VITRO LIPOLYSIS ORAL ABSORPTION IONIC LIQUIDS DOSAGE FORMS FORMULATIONS BIOAVAILABILITY SUPERSATURATION SOLUBILITY
36
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.
NEW YORK
0724-8741
10.1007/s11095-019-2590-y
Grant Details