Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel

Abstract

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) ⿿ a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound ⿿ has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2⿿91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75⿿131μg/day or 37⿿66μg/day for DPV, and either 96⿿150μg/day or 37⿿57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception.