In Vitro Investigation and Characterization of Silicone Matrix IVR Loaded with Levonorgestrel: A Propper Method for Hormon Replacement Therapy

Introduction: Among 3 to 30 percent of women of reproductive age, experience abnormal uterine bleeding (AUB). Vaginal rings are one of the systems of interest for the local delivery of hormones that due to their polymeric structure allow prolonged release of drug. In this study, the design and fabrication of matrix vaginal rings containing levonorgestrel (LNG) were investigated. Methods: In this experimental study, at first, two pieces of aluminum mold were designed, then base (A) and cross-linker parts (B) of polymer with LNG were mixed and 48 polymeric rings containing LNG were manufactured by injection molding method. To achieve the desired drug release values in a given time, the effect of temperature, rpm, release environment, different initial loading, cross-linker percentage and a mathematical model to predict release and swelling test were investigated. Results:  As a result of the experiments, it was revealed that with increasing drug loading, the release rate rises, while increasing the cross-linker percentage reduced the drug release. Finally, the ring A:B=100:9.5 with an initial loading of 0.2 % LNG relative to silicon was selected as an appropriate ring, and release experiments were performed at 37 °C, shaker speed of 80 rpm, and release medium containing 10 % ethanol. Drug release values were measured by spectrophotometer and analyzed by SPSS statistical software version 16. Conclusion: Based on the results, it can be deduced that matrix vaginal ring containing LNG is a suitable drug delivery system for prolonged release of LNG for treatment of AUB that depending on the drug initial loading and cross-linker percentage, the required diffusion coefficient, and release rate can be achieved in a certain time.