Controlled release of levonorgestrel from silicone vaginal rings for targeted management of abnormal uterine bleeding: a comparative in vitro study

Abnormal uterine bleeding affects women of reproductive age, highlighting the need for effective and sustainable hormonal treatment. This study evaluated two different vaginal rings, including a Reservoir Solution Core (R-IVR) and Matrix Dispersion (M-IVR), to optimize drug release for the treatment of Abnormal Uterine Bleeding (AUB). R-IVR rings were fabricated using pharmaceutical grade silicone tubing and filled with levonorgestrel (LNG) paraffin solution at different concentrations. M-IVRs were produced by injection molding, and different ratios of silicone base to crosslinker were used to control the drug permeability. Drug release was investigated for more than 20 days for both IVR prototypes in vitro. R-IVRs exhibited an initial burst release, and subsequently, a daily release ranging from 20 μg/day to 80 μg/day. M-IVRs showed higher release rates, while increasing the percentage of the crosslinker decreased the release rate. The optimized prototype M-IVR2-0.9, demonstrated an average release of 73 μg/day of LNG. Both vaginal ring designs can provide controlled release of LNG within the therapeutic window and have high potential for the tunable treatment of AUB. The results of this study support the development of vaginal-ring-based hormonal therapies that can be customized to patients' individual needs.