Testing potential dosage form strategies for intestinal lymphatic drug transport: studies in the rat

W. N.A. Charman, T. Noguchi, V. J. Stella

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Abstract

The effect of some differing formulation strategies on the intestinal lymphatic transport of DDT has been evaluated. Drug-lipid vehicle combinations were administered to conscious rats by the peroral route, or to anesthetized rats by intraduodenal infusion. A 2 mg dose of DDT was dissolved in either 200 μl of peanut oil (triglyceride) or 200 μl of oleic acid (fatty acid) and administered to mesenteric lymph duct cannulated rats. During the post-dosing period, there were no significant differences in the percent dose of DDT collected in intestinal lymph when administered in peanut oil by either the peroral (24.3 ± 3.0% dose) or intraduodenal route (19.9 ± 1.8% dose). When the same dose of DDT was administered in oleic acid, greater lymphatic transport occurred when the DDT-lipid vehicle combination was administered intraduodenally (35.7 ± 2.1% dose), rather than perorally (16.6 ± 3.3% dose). It is postulated that these differences may be due to differing effects of the fatty acid and triglyceride lipids on gastric emptying and/or intestinal motility. When considering that a drug product can release a drug-lipid combination at different sites within the gastrointestinal tract (stomach or small intestine), these results may have a bearing on potential formulation strategies and dosage form design for the enhancement of the lymphatic transport of lipophilic drugs. Simulated sustained release preparations using a 200 μl/8 h infusion of peanut oil containing 2 mg of DDT did not afford significantly enhanced lymphatic transport of DDT when compared to a 200 μ1/2 h infusion of the same drug-lipid combination. There was a large amount of variation in the lymphatic transport of DDT administered at the slower rate of infusion. When animals were pre-dosed with 75 μl of peanut oil prior to infusion of 2 mg DDT in 200 μl over 8 h, there was much less variability in the lymphatic transport of DDT. It appears that there may. be an optimal rate of lipid input into the small intestine to trigger, or initiate, significant lymphatic transport of lipophilic molecules.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume33
Issue number1-3
DOIs
Publication statusPublished - 1 Jan 1986
Externally publishedYes

Keywords

  • DDT
  • Dosage form strategy
  • Lymphatic transport
  • Site of administration
  • Sustained release

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