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

René Holm; Christopher J H Porter; Glenn A Edwards; Anette Müllertz; Henning G Kristensen; William N Charman

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

René Holm, Christopher J H Porter, Glenn A Edwards, Anette Müllertz, Henning G Kristensen, William N Charman

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

148 Citationer (Scopus)

Abstract

Udgivelsesdato: 2003-Sep

Originalsprog	Engelsk
Tidsskrift	European Journal of Pharmaceutical Sciences
Vol/bind	20
Udgave nummer	1
Sider (fra-til)	91-7
Antal sider	6
ISSN	0928-0987
Status	Udgivet - 2003

Bibliografisk note

Keywords: Administration, Oral; Animals; Biological Availability; Biological Transport; Dogs; Drug Delivery Systems; Emulsions; Lymphatic System; Models, Animal; Phenanthrenes; Time Factors; Triglycerides

Citationsformater

Holm, R., Porter, C. J. H., Edwards, G. A., Müllertz, A., Kristensen, H. G., & Charman, W. N. (2003). 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. European Journal of Pharmaceutical Sciences, 20(1), 91-7.

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. / Holm, René; Porter, Christopher J H; Edwards, Glenn A; Müllertz, Anette; Kristensen, Henning G; Charman, William N.

I: European Journal of Pharmaceutical Sciences, Bind 20, Nr. 1, 2003, s. 91-7.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Holm, R, Porter, CJH, Edwards, GA, Müllertz, A, Kristensen, HG & Charman, WN 2003, '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', European Journal of Pharmaceutical Sciences, bind 20, nr. 1, s. 91-7.

Holm, René ; Porter, Christopher J H ; Edwards, Glenn A ; Müllertz, Anette ; Kristensen, Henning G ; Charman, William N. / 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. I: European Journal of Pharmaceutical Sciences. 2003 ; Bind 20, Nr. 1. s. 91-7.

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title = "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",

abstract = "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-sn-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.",

author = "Ren{\'e} Holm and Porter, {Christopher J H} and Edwards, {Glenn A} and Anette M{\"u}llertz and Kristensen, {Henning G} and Charman, {William N}",

note = "Keywords: Administration, Oral; Animals; Biological Availability; Biological Transport; Dogs; Drug Delivery Systems; Emulsions; Lymphatic System; Models, Animal; Phenanthrenes; Time Factors; Triglycerides",

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T1 - 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

AU - Holm, René

AU - Porter, Christopher J H

AU - Edwards, Glenn A

AU - Müllertz, Anette

AU - Kristensen, Henning G

AU - Charman, William N

N1 - Keywords: Administration, Oral; Animals; Biological Availability; Biological Transport; Dogs; Drug Delivery Systems; Emulsions; Lymphatic System; Models, Animal; Phenanthrenes; Time Factors; Triglycerides

PY - 2003

Y1 - 2003

N2 - 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-sn-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.

AB - 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-sn-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.

M3 - Journal article

C2 - 13678797

VL - 20

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EP - 97

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

IS - 1

ER -