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Mol Pharm. 2016 Oct 3;13(10):3417-3426. Epub 2016 Aug 30.

In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems.

Author information

1
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, Copenhagen 2100, Denmark.
2
Faculty of Pharmaceutical Sciences, University of British Columbia , 2146 East Mall, Vancouver, BC V6T 1Z3, Canada.
3
College of Pharmacy and Nutrition, University of Saskatchewan , E3122-104 Clinic Place, Saskatoon, SK S7N 2Z4, Canada.

Abstract

Precipitation of poorly water-soluble drugs from lipid-based drug delivery systems (LbDDS) has been studied extensively during in vitro lipolysis but has never been shown in vivo. The aim of this study was therefore to investigate if drug precipitation can occur from LbDDS during transit of the gastrointestinal tract in vivo. Rats were administered 300 μL of either of two LbDDS (LbDDS I and LbDDS II) loaded with danazol or fenofibrate (or paracetamol to assess gastric emptying). The rats were euthanized at various time points after administration of both LbDDS containing either drug, and the contents of the stomach and proximal part of the small intestine were harvested. The contents were analyzed for crystalline drug by X-ray powder diffraction and polarized light microscopy. No drug precipitation was evident in the stomach or the intestine after administration of LbDDS I containing danazol at the tested time points. Fenofibrate precipitation was absent in the stomach initially after administration of LbDDS I, but was evident in the stomach 90 min after dosing. No crystalline fenofibrate was observed in the intestine. Danazol and fenofibrate precipitation was evident in the stomach following administration of LbDDS II containing either drug, but not in the intestine at the tested time point. Drug precipitation from LbDDS was observed in the stomach, but not in the intestine, which is contrary to what in vitro lipolysis data (obtained under human GI conditions) suggests. Thus, precipitation of drugs from LbDDS in vivo in rats is much lower than might be anticipated from in vitro lipolysis data.

KEYWORDS:

drug precipitation; gastric digestion; gastric emptying; in vitro lipolysis; in vivo; lipid-based drug delivery systems; poorly soluble drugs

[Indexed for MEDLINE]

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