Correlation between digestion of the lipid phase of smedds and release of the anti-HIV drug UC 781 and the anti-mycotic drug enilconazole from smedds.
The present studies were conducted primarily to compare the drug release process of the anti-HIV drug UC781 from three different smedds to the smedds digestion profile. The influence of every formulation component on the digestion process, measured as the release of fatty acids, was determined. In addition, the release of the antimycotic drug enilconazole from a smedds was investigated as well in order to study the influence of the type of incorporated drug on oil digestion. Simulsol 1292, Tween 80, Cremophor RH40, ethanol and both drugs reduced the fatty acid release. C8, C10 and C12 fatty acids, originating from oil hydrolysis, were able to reverse the inhibitory effect of phospholipids present in the release medium. Similarly Cremophor RH40 lost its inhibitory capacities in combination with Captex 200P hydrolysis. In addition, UC781 did not decrease fatty acid release in combination with a Captex 200P-Tween 80-ethanol mixture. The release of UC781 from smedds significantly increased compared to the dissolution of the pure drug. The drug release profiles were characterized by rapid and complete release followed by precipitation. In order to detect possible correlations between drug release and oil digestion, release results were compared to those of vehicle digestion experiments. Contrary to what one would assume, a higher extent of fatty acid liberation did not enhance drug release. In other words, drug release does not seem to be driven by the extent of lipid digestion.
Goddeeris
C
C
Laboratory of Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Leuven, Belgium.
Coacci
J
J
Van den Mooter
G
G
D000813:Anilides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D005227:Fatty Acids / Q000378:metabolism; D005663:Furans / Q000737:chemistry*; D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry*; D008049:Lipase / Q000378:metabolism; D009821:Oils / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013854:Thioamides; D013997:Time Factors
D000813:Anilides; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D005227:Fatty Acids; D005663:Furans; D007093:Imidazoles; D009821:Oils; D012997:Solvents; D013501:Surface-Active Agents; D013854:Thioamides; D000431:Ethanol; C017435:enilconazole; D008049:Lipase; C100668:UC-781