AROMATASE INHIBITOR-RELEASING INTRAVAGINAL DEVICE

摘要

Described herein is an intravaginal device that provides biologically active circulating concentrations of an aromatase inhibitor for at least about of 4 days. Three compounds with estradiol inhibitory capability (letrozole, anastrozole and fenbendazole) were tested in vitro using bovine granulosa cell culture. Letrozole was found to be the most efficient and potent inhibitor. Liposome-based and a wax-based formulations were used to assess letrozole diffusion through bovine vaginal mucosa in a diffusion chamber study. Samples were collected over a 24 h period. The wax-based vehicle was selected for further development of a letrozole intravaginal device based on its steady release rate. In an in vivo study in cattle, 3 different intravaginal devices containing 3 g of letrozole were tested: Wax (with 1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine, DOPE) +gel coat (n=2), Wax+gel coat (n=4) and Wax (n=4). Blood samples were collected serially from time 0 to 120 h, and daily thereafter to measure circulating concentrations of letrozole by LC/MS/MS. The addition of a letrozole-containing gel coating improved initial absorption and hastened the increase on plasma concentrations of the active ingredient, while the letrozole-containing wax-based vehicle maintained prolonged delivery from the intravaginal device.

主权项

1. A delivery vehicle for the delivery of an aromatase inhibitor to a mammal, said vehicle comprising: a wax-delivery system; and an aromatase inhibitor; wherein said vehicle is suitable for delivering said aromatase inhibitor to the plasma of said mammal.