Formulation development of a multipurpose vaginal ring for non-hormonal contraception and HIV prevention

Building on recent marketing approvals for the dapivirine (DPV) vaginal ring for HIV prevention in various African countries, efforts have been underway to develop new multipurpose rings that can simultaneously prevent HIV infection and unintended pregnancy. For example, a combination ring releasing DPV and the progestin levonorgestrel is in active development. There is an increasing demand from women for non-hormonal contraceptive options, mostly due to concerns over safety and side effects with hormonal products. Here, we describe our efforts to develop a ring offering sustained release of DPV, copper ions (Cu2+) and zinc ions (Zn2+) for HIV prevention and non-hormonal contraception.
Four matrix-type silicone elastomer ring formulations – containing (i) 25 mg DPV, (ii) 25 mg DPV + 10% hydroxypropylmethylcellulose (HPMC), 25 mg DPV + 10% copper sulphate anhydrous + 10% zinc sulphate monohydrate, and (iv) 25 mg DPV + 10% copper sulphate anhydrous + 10% zinc sulphate monohydrate + 10% HPMC – were prepared by injection molding. HPMC was included as a release modulator. Rings were tested for in vitro release, swelling, and mechanical performance.
All ring formulations were manufactured successfully (initial dimensions and weights: ~56.8×7.2 mm; 7.2–8.6 g). Mechanical properties of the rings fell within the range of commercial ring products; 1.8–4.3 N for 20 mm compression force, and Shore M hardness values 34–67. Sustained release of DPV (1.05–2.68 mg/day1/2), Cu2+ ions (1.12–2.75 mg/day1/2) and Zn2+ ions (0.82–3.17 mg/day1/2) were measured over 30 days. DPV release was significantly increased when formulated with other actives, and incorporation of HPMC significantly increased release of DPV, Cu2+ and Zn2+ ions. In vitro release quantities were considered sufficient for clinical efficacy, based on previously reported data. The study demonstrates the potential for a multipurpose ring device releasing DPV and non-hormonal contraceptive actives.