Towards a dapivirine and levonorgestrel multipurpose vaginal ring: Investigations into the reaction between levonorgestrel and addition-cure silicone elastomers

Robert Malcolm, Yahya Dallal Bashi, Clare F. McCoy, Diarmaid Murphy, Peter Boyd, Patrick Spence, Kyle Kleinbeck, Brid Devlin

Research output: Contribution to journalArticle

4 Citations (Scopus)
22 Downloads (Pure)

Abstract

With a dapivirine-releasing vaginal ring having successfully completed late-stage clinical testing for HIV prevention and currently undergoing regulatory review, there is now growing interest in next-generation multipurpose prevention technologies that seek to combine antiretroviral and contraceptive drugs within a single product. Here, we focus on ongoing efforts to develop a silicone elastomer vaginal ring releasing both dapivirine and levonorgestrel. Specifically, we evaluate various strategies aimed at both better understanding and reducing the tendency of levonorgestrel to bind with the elastomer, including: (i) formulation and post-manufacturing strategies aimed at reducing the extent of levonorgestrel reaction with addition-cure silicone elastomers; (ii) evaluation of a simple silicone system to model the complex elastomer; (iii) use of model compounds representing the enone and ethinyl moieties of levonorgestrel to probe the mode of addition of levonorgestrel to addition-cure silicone elastomers; and (iv) solution and solid-state 13C-NMR analysis to probe the structural features of the levonorgestrel-silicone system. The results demonstrate that both the enone and ethinyl groups within levonorgestrel undergo hydrosilylation reaction with hydrosiloxane groups in the silicone elastomer leading to binding. The results also highlight potential strategies for further optimising the dapivirine+levonorgestrel silicone vaginal ring formulation to ensure that the levonorgestrel is available for release.
Original languageEnglish
Article number118574
JournalInternational Journal of Pharmaceutics
Early online date26 Jul 2019
DOIs
Publication statusPublished - 05 Oct 2019

Keywords

  • Multipurpose prevention technology
  • Dapivirine
  • HIV microbicide
  • MPT
  • Intravaginal ring
  • Levonorgestrel
  • Silicone elastomer
  • Hydrosilylation

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