• Singer, Patrick
• Boyd, Peter
• Zhao, Xinyu
• Shen, Xin
• Lamb, Dolores
• Malcolm, Karl
• Mitchell, Lyann
• Mccoy, Clare
• Kumar, Narender

Abstract

Marketed contraceptive intravaginal vaginal rings (IVR) rely upon sustained/controlled release of either a progestin (e.g., Progering®)or a progestin/estrogen combination (e.g., NuvaRing®, Annovera®). Here we report formulation development and testing of a new non-hormonal multipurpose IVR incorporating three actives – copper sulphate anhydrous (CSA), zinc lactate anhydrous (ZLA), and lactide (L; hydrolyses to lactic acid, LA) (aka. ‘CZL’ IVR) – and offering spermicidal, antibacterial and antiviral activity. Matrix-type silicone elastomer IVRs containing 30%CSA, 30%L, 10%CSA+20%L, 10%CSA+10%ZLA+10%L, and 10%CSA+10%ZLA+20%Lwere prepared by mixing the various actives with a medical-grade addition-cure silicone elastomer and injecting/curing the mixes at 115°C using custom molds. VRs were tested for weight, dimensions (outer and cross-sectional diameter), thermal behaviour (via DSC and TGA), in vitro release (deionised water, 37 °C ), pH reduction, and mechanical properties.All IVR formulations were successfully manufactured, producing VRs of well-defined dimensions (~57.4 x ~7.3 mm), ring weights that varied with type, quantity and combinationof actives (7.8–9.3 g), and mechanical properties similar to marketed IVR products (20 mm compression force and Shore M hardness values ranged 0.8–4.3 N and 41–67, respectively). The actives were not impacted by the VR manufacturing process, as evidenced by DSC and TGA data. Sustained and continuous release of copper and zinc ions (2–31 and 1–17 mg/day) and lactide/lactic acid (11–86 mg/day) was observed for all IVRs over 30 days; these values are considered in the ballpark for clinical efficacy based on in vitro sperm motility/antibacterial/antiviral data (see other poster). IVRs containing lactide maintained pH of the release medium within the range 2.2–4.6, consistent with (i) release of lactide and rapid hydrolysis to lactic acid and (ii) the pH modulating effects associated with CSA and ZLA. The data support the continued development of the multipurpose CZL IVR concept.<br/><br/>

Topics

• zinc
• hardness
• copper
• thermogravimetry
• differential scanning calorimetry
• curing
• elastomer