Intestinal lymphatic transport of DDT and Saquinavir : the role of lipid based formulations and modulators of P-Glycoprotein and Cytochrome P450
Citation:Brendan T. Griffin, 'Intestinal lymphatic transport of DDT and Saquinavir : the role of lipid based formulations and modulators of P-Glycoprotein and Cytochrome P450', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2002, pp 311
Griffin TCD THESIS 6801 Intestinal lymphatic.pdf (PDF) 176.0Mb
The experiments in this thesis represent biopharmaceutical investigations, performed in an attempt to evaluate potential dosage form strategies designed to promote the intestinal lymphatic transport of lipophilic compounds. DDT is a highly lipophilic model compound, which is routinely used in mechanistic lymphatic transport studies. Saquinavir is a recently approved, highly lipophilic, potent HIV protease inhibitor, which exhibits poor bioavailability due to poor dissolution and absorption characteristics and extensive first pass metabolism. Initially, the solubilization capacities of a series of lipid micellar systems for both lipophilic compounds were examined. The lipid vehicles investigated included simple and mixed micelles, of both naturally occurring (e.g. bile salts) and synthetic (e.g. cremophor EL and TPGS) surfactants. The saturation solubility of both DDT and saquinavir in the presence of these micellar systems were all significantly improved, relative to aqueous solubility. The solubility of both lipophilic compounds in mixed micelles, containing the long chain, oleic acid, increased with increasing fatty acid content, relative to the simple micelles. The micellar systems produced from the synthetic surfactants, TPGS and Cremophor EL, generally displayed a greater solubilization potential for both lipophilic compounds, compared to the bile salt micelles, although some differing solubilization mechanisms between naturally occurring and synthetic micelles were observed.
Author: Griffin, Brendan T.
Advisor:O'Driscoll, Caitriona M.
Qualification name:Doctor of Philosophy (Ph.D.)
Publisher:Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
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Type of material:thesis
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