Despite a long history of incorporating steroids into silicone elastomers for drug delivery applications, little is presently known about the propensity for irreversible drug binding in these systems. In this study, the ability of the contraceptive progestin levonorgestrel to bind chemically with hydrosilane groups in addition-cure silicone elastomers has been thoroughly investigated. Cure time, cure temperature, levonorgestrel particle size, initial levonorgestrel loading and silicone elastomer type were demonstrated to be key parameters impacting the extent of levonorgestrel binding, each through their influence on the solubility of levonorgestrel in the silicone elastomer. Understanding and overcoming this levonorgestrel binding phenomenon is critical for the ongoing development of a number of drug delivery products, including a multi-purpose technology vaginal ring device offering simultaneous release of levonorgestrel and dapivirine – a lead candidate antiretroviral microbicide – for combination HIV prevention and hormonal contraception.
Murphy, D.J.; Boyd, P.; McCoy, C.F.; Kumar, S.; Holt, J.D.S.; Blanda, W.; Brimer, A.N.; Malcolm, R.K. Controlling levonorgestrel binding and release in a multi-purpose prevention technology vaginal ring device. Journal of Controlled Release (2016) 226: 138-147. [DOI: 10.1016/j.jconrel.2016.02.020]