P14.04
Background: IPM's silicone-based Dapivirine Vaginal Ring is in Phase III trials as a vaginal microbicide for 1 month continuous use. New formulations have been assessed with in vitro drug release of greater than 90 days. By extending the use duration per ring, the overall production cost per patient per month may be decreased to nearly one third that of the monthly dapivirine vaginal ring.
Methods: Silicone vaginal rings manufactured at Queen's University Belfast using similar manufacturing processes as IPM's monthly dapivirine vaginal ring were produced as either dapivirine (DPV) only (25 and 200 mg) or a combination of DPV (200 mg) & LNG (32 mg). Nusil Med-4870® (a Pt-catalyzed, addition cured silicone polymer) was used to produce rings with an overall diameter of 5.67cm, cross-section diameter of 7.82 mm and weighing 8g (160°C cure for 60 sec).
Daily in vitro release (IVR) of DVP and/or LNG was assessed up to 92 days in 50 mL of 1:1 IPA: water. Media was assayed by HPLC for DPV and LNG.
Results: The DPV IVR target was 105 μg, which is the day 28 (25 mg) Dapivirine Vaginal Ring release rate. Formulations containing 200 mg DPV exceeded the target (d30=628 μg; d60=437 μg; d92=301 μg). In addition, when formulated in combination with LNG, DPV IVR (μg/day) remained above the target (d30=634; d60=454; d92=299). LNG IVR was also above target (35 μg/day) for all 92 days tested (d30=155; d60=91; d92=46).
The day 1 release for a 200mg DPV ring (4132 μg DPV alone; 6038 μg DPV with LNG) and for a 32 mg LNG ring (684 μg) remained at levels below those established as safe in nonclinical toxicity studies.
Conclusions: The IVR data presented indicate that it may be possible to produce a DPV-only microbicide ring and a DPV -LNG combination microbicide and contraceptive ring for use over 90 days using a silicone matrix ring. Furthermore, within the given range, elevation of DPV loading (or co-loading with LNG) does not increase in vitro release to unsafe levels.
