ASSESSMENT OF THE PROGESTIN POLYMERIC VAGINAL FILMS BY ANOPTIMIZED SOLVENT-CAST PLATFORM

Background: Although many birth control options are provided for women nowadays, the rate of unintended pregnancies remains high internationally and nationally. Novel contraceptive methods, such as contraceptive vaginal films, are needed to meet the users’ biological, social and economic needs. An established solvent-cast platform can potentially be an option for vaginal administration of progestins for contraception. The goal of this work is to the feasibility and versatility of film platform for incorporating progestins. Methods: A panel of progestins, desogestrel (DES), etonogestrel (ENG), dienogest (DNG) and ulipristal acetate (UPA) were chosen based on their different physiochemical properties and availability. The progestins were incorporated into a fastdissolved film formulation and the films were evaluated for appearance; weight; thickness; puncture strength; water content; disintegration time and drug content. Stability for each of these parameters was monitored for 3 months under two storage conditions (25°C/65%RH; 40°C/75%RH). Additionally, in vitro dissolution was investigated using a USP 1 method. Results: All four progestins could be successfully incorporated into the film formulation, despite their different lipophilicities. When comparing across progestin films for two dosing levels, differences were observed with respect to the physical characteristics ofthe progestin film. A decrease in drug content was observed for desogestrel (DES) films over 3 months. However, other progestin films remained stable throughout 3 months. Film physical properties were consistent throughout this time frame. The in vitro dissolution study showed that all four progestins released 80% of the drug within 15 minutes. Conclusion: Results demonstrated that the progestins could be formulated as polymeric vaginal films, despite their different physiochemical properties. For ENG, DNG and UPA films, the physical characterizations of the progestin films remained stable for at least 3 months. However, the amount of progestin located into the film impacted the puncture strength and water content of the films. This project demonstrated the capacity of the film to be applied for vaginal delivery of progestins.