Amphiphilic vehicles improve the oral bioavailability of a poorly soluble HIV protease inhibitor at high doses1Portions of this work were presented at Journeé Galéniques de Saint-Rémy de Provence, May 1994, and at the AAPS Eastern Regional Meeting, June 1994.1

摘要: DMP 323 is the first clinical candidate from a novel series of HIV protease inhibitors having cyclic urea structural backbone. In dogs dosed with glycol-based vehicles, was approximately 50% orally bioavailable after 100 mg dose, but bioavailability almost 10-fold lower when 350 dose administered. Since has very low water solubility, it expected that this loss at high due to drug precipitation in aqueous fluids gastrointestinal tract. Clinically, doses were desired so as maximize antiviral effects. Therefore, formulation strategies improve examined. Bioavailability not improved using formulations consisting glycols concentrations added surfactants, or solid dispersions PEG PEG/PVP matrices. An alternative approach use comprised primarily an amphiphilic material such Gelucire 44/14 (a mixture glycerides and esters). increased semi-solid formulation, compared 6% value observed glycol vehicles. solubility dissolution rate, did other materials HLB values. Oral determined by solubilization afforded vehicle diluted into environment, dose. Amphiphilic vehicles could be used administer without compromising oral bioavailability. A limitation volume required.