In the present study, we investigated the feasibility of the vaginal administration of drospirenone silicone IVR. The in vitro release characteristics of matrix-type and reservoir-type IVR were compared under sink conditions in 21 days. At the same time, API excipients compatibility and preformulation study was performed by HPLC, IR, and DSC methods. Biocompatibility of reservoir system was evaluated by tolerability on tissue level in rats. It was found that, under strong light exposure, high temperature, and high humidity conditions, drospirenone and excipients had no significant interactions. The daily release of reservoir-type IVR was about 0.5 mg/d sustaining 21 days, which significantly decreased the burst effect compared with the matrix system. When drospirenone was modified by the PVPk30 in the reservoir system formulation, the daily release rate increased to 1.0 mg/d sustaining 21 days. The cumulative release of reservoir-type IVR was fitted to zero release equation. In addition, biocompatibility of drospirenone IVR system in this dosage is safe. It is feasibility feasibile to further developed for safe, convenient, and effective contraceptive drug delivery with reduced dosing interval. 1. Introduction Drospirenone？？ (6b,7b,15b,16b-dimethylene-3-oxo-17a-pregn-4-ene-21,17-carbolactone) is an analogue of the antimineralocorticoid spironolactone (Figure 1) that is synthesized from androstenolone. Unlike other progestogens, drospirenone, an analogue of spironolactone, has biochemical and pharmacologic profiles similar to endogenous progesterone, especially regarding antimineralocorticoid and antiandrogenic activities. Drospirenone counteracts the estrogen-induced stimulation of the renin-angiotensin-aldosterone system and blocks testosterone from binding to androgen receptors. Because of these characteristics, it has the potential to reduce body weight, blood pressure, and low-density lipoprotein levels and to enhance high-density lipoprotein levels. As a combination, oral contraceptive, drospirenone with ethinyl estradiol, is effective and has positive effects on weight and lipid levels [1]. Figure 1: Drospirenone. Drospirenone has rapid oral absorption, its peak plasma concentration time is about 60–90？min, and the half-life is 30–35？h [2]. This product is to be administrated daily, otherwise it will affect the contraceptive effect. Therefore, sustained release of drug is preferred above the daily administration. Intravaginal rings (IVR) can serve as an alternative for the daily administration of tablets [3]. The contraceptive vaginal ring offers
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