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Structured Triglyceride Vehicles for Oral Delivery of Halofantrine: Examination of Intestinal Lymphatic Transport and Bioavailability in Conscious Rats

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Abstract

Purpose. To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats.

Methods. Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration of halofantrine in blood and lymph samples was analyzed by HPLC.

Results. Both the lymphatic transport and the total absorption of halofantrine were enhanced by the use the MLM triglyceride. The estimated total absorption of halofantrine in the lymph cannulated animals was higher than in the nonlymph cannulated animals, and this was most pronounced for the animals dosed with the structured triglycerides.

Conclusions. Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.

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Author notes

  1. René Holm

    Present address: Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, 2100, Copenhagen, Denmark

Authors and Affiliations

  1. Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, 2100, Copenhagen, Denmark

    Anette Müllertz & Henning G. Kristensen

  2. Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Victoria, 3052, Australia

    Christopher J. H. Porter & William N. Charman

Authors
  1. René Holm
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  2. Christopher J. H. Porter
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  3. Anette Müllertz
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  4. Henning G. Kristensen
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  5. William N. Charman
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Correspondence to Anette Müllertz.

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Holm, R., Porter, C.J.H., Müllertz, A. et al. Structured Triglyceride Vehicles for Oral Delivery of Halofantrine: Examination of Intestinal Lymphatic Transport and Bioavailability in Conscious Rats. Pharm Res 19, 1354–1361 (2002). https://doi.org/10.1023/A:1020311127328

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