Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides

The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water-...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2003-09, Vol.20 (1), p.91-97
Main Authors: Holm, René, Porter, Christopher J.H., Edwards, Glenn A., Müllertz, Anette, Kristensen, Henning G., Charman, William N.
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiparasitic agents
Bioavailability
Biological and medical sciences
Biological Availability
Biological Transport
Canine
Dogs
Drug Delivery Systems
Emulsions
General pharmacology
Halofantrine
Lymphatic System - metabolism
Lymphatic transport
Medical sciences
Models, Animal
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phenanthrenes - administration & dosage
Phenanthrenes - blood
Phenanthrenes - pharmacokinetics
SMEDDS
Structured triglyceride
Time Factors
Triglycerides - metabolism
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Summary:The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water-soluble drug, halofantrine, were investigated in fasted lymph cannulated canines. Two different structured triglycerides were incorporated into the SMEDDS; 1,3-dioctanoyl-2-linoleyl-s n-glycerol (C8:0-C18:2-C8:0) (MLM) and 1,3-dilinoyl-2-octanoyl- sn-glycerol (C18:2-C8:0-C18:2) (LML). A previously optimised SMEDDS formulation for halofantrine, comprising of triglyceride, Cremophor EL, Maisine 35-1 and ethanol was selected for bioavailability assessment. The extent of lymphatic transport via the thoracic duct was 17.9% of the dose for the animals dosed with the MLM SMEDDS and 27.4% for LML. Also the plasma availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption pathways. The MLM formulation produced a total bioavailability of 74.9%, which is higher than the total absorption previously observed after post-prandial administration. This could indicate the utility of disperse lipid-base formulations based on structured triglycerides for the oral delivery of halofantrine, and potentially other lipophilic drugs.
ISSN:0928-0987
1879-0720
DOI:10.1016/S0928-0987(03)00174-X