Journal
JOURNAL OF CONTROLLED RELEASE
Volume 226, Issue -, Pages 138-147Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2016.02.020
Keywords
Vaginal ring; Silicone elastomer; Hydrosilylation; Controlled release; Drug delivery; Implantable devices
Funding
- International Partnership for Microbicides
- Ministry of Foreign Affairs of the Netherlands
- American people through the United States Agency for International Development (USAID) through the President's Emergency Plan for AIDS Relief (PEPFAR)
- National Overseas Scholarship from the Government of India
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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. (C) 2016 Elsevier B.V. All rights reserved.
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