Mechanical testing methods for drug-releasing vaginal rings.

Vaginal rings (VRs) are currently marketed for contraceptive or hormone regulation purposes, and investigationally, have been widely reported for delivery of antiretrovirals to reduce HIV transmission. To date, there is no national or international standard for the mechanical testing and minimum performance characteristics of any VR based products. Here, we describe a series of mechanical tests examining the durometer hardness, static and dynamic compression response, tensile properties and twist resistance of vaginal rings. The tests were conducted on currently marketed VRs and a number of the International Partnership for Microbicides' (IPM) investigational VR formulations. With wider application in the field, the tests described herein could form the basis for a more standardised approach to the mechanical testing of VRs.

Controlling levonorgestrel binding and release in a multi-purpose prevention technology vaginal ring device.

Despite a long history of incorporating steroids into silicone elastomers for drug delivery applications, little is presently known about the propensity for irreversible drug binding in these systems. In this study, the ability of the contraceptive progestin levonorgestrel to bind chemically with hydrosilane groups in addition-cure silicone elastomers has been thoroughly investigated. Cure time, cure temperature, levonorgestrel particle size, initial levonorgestrel loading and silicone elastomer type were demonstrated to be key parameters impacting the extent of levonorgestrel binding, each through their influence on the solubility of levonorgestrel in the silicone elastomer. Understanding and overcoming this levonorgestrel binding phenomenon is critical for the ongoing development of a number of drug delivery products, including a multi-purpose technology vaginal ring device offering simultaneous release of levonorgestrel and dapivirine - a lead candidate antiretroviral microbicide - for combination HIV prevention and hormonal contraception.

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

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.