OA26.03
Background: By extending the use duration of vaginal rings (VRs), the overall production cost per patient per month can be greatly reduced. Matrix-type ring designs produce an initial burst of drug release, and concentrations during the burst must be maintained within safe limits. This constrains both the maximum drug load and, in turn, the use duration of a matrix ring. By contrast, reservoir-type VRs comprise a drug-loaded reservoir surrounded by a rate-controlling non-medicated sheath, such that initial burst release is minimised and constant daily release rates are achieved. In this way, greater drug loadings and longer use periods are possible. Here, we report the development of reservoir VRs formulations containing dapivirine (DPV) and various contraceptive steroids.
Methods: Reservoir VRs were manufactured with injection molded cores containing ethinyl estradiol (EE), etonogestrel (ETO), levonorgestrel (LNG) or DPV. Addition- and condensation-cured silicone cores were tested. All cores were overmolded with a blank 1.5 mm addition-cured silicone sheath. In-vitro release was assessed for up to 60 days.
Results: VRs comprising addition cured silicone cores and blank addition cured silicone sheath layers provided zero order release of DPV (95 μg/day) and LNG (30 μg/day), but not EE (detectable release on days 2 to 10 only) or ETO (no detectable release at any time). Rings comprising a condensation-cured silicone core provided zero order release of DPV (119 μg/day), EE (328 μg/day, days 4 to 18), ETO (422 μg/day, days 4 to 18) and LNG (69 μg/day).
Conclusions: Reservoir-type VRs offering zero order release kinetics have potential as a multipurpose prevention technology (MPT) product for contraception and HIV-prevention with use duration of several months. However, the contraceptive hormones require careful selection of the silicone polymer system to ensure adequate release, while DPV is readily released from both types tested.
