Effect of Crosslinking on the Physicochemical Properties of Polydimethylsiloxane-based Levonorgestrel Intrauterine Systems

Polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs) such as Mirena® are long-acting drug-device combination products designed to release LNG for contraceptive purposes up to 6 years. LNG-IUSs consist of a hollow cylindrical drug-PDMS reservoir mounted with a polyethylene frame and covered by an outer PDMS membrane. PDMS is the release-controlling excipient present in both the matrix and the outer membrane. The degree of PDMS crosslinking is a key parameter in LNG-IUS manufacturing, dictating the elasticity and mechanical strength (which are critical parameters in molding and demolding of the cylindrical reservoirs). In addition, elasticity and mechanical strength are also important to prevent deformation during insertion into the uterine cavity. The objectives of this study were to investigate the impact of PDMS crosslinking on the physicochemical properties of LNG-IUSs and to develop appropriate testing methods for characterization of their mechanical strength. Formulations with different degrees of crosslinking were prepared by varying the ratio of the PDMS elastomer base and the crosslinking agent. A novel solvent swelling and extraction method was developed to determine the degree of PDMS crosslinking. The extent of crosslinking was also characterized via FTIR, Raman, H NMR, DSC, TGA and dynamic mechanical analysis. As expected, formulations with higher degrees of crosslinking showed lower crystallinity. Interestingly, the less crystalline formulations showed higher Tg values and storage moduli compared to the high crystalline formulations, implying that crosslinking is the predominant parameter governing the physicochemical and mechanical properties in LNG-IUSs. Correlations were established between PDMS crosslinking and the physicochemical properties of LNG-IUSs which will be useful for quality control purposes during formulation screening and development. A better understanding of the physicochemical characteristics of these complex products will facilitate drug product development.