Solid state 13C NMR spectroscopy provides direct evidence for reaction between ethinyl estradiol and a silicone elastomer vaginal ring drug delivery system

Clare F. McCoy, David C. Apperley, Robert Malcolm, Bruce Variano, Heather Sussman, Daniel Louven, Peter Boyd, R. Karl Malcolm

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
191 Downloads (Pure)

Abstract

Steroid molecules have a long history of incorporation into silicone elastomer materials for controlled release drug delivery applications. Previously, based on in vitro release testing and drug content data, we demonstrated indirectly that the contraceptive progestin levonorgestrel chemically and irreversibly binds to addition cure silicone elastomers via a hydrosilylation reaction between its ethynyl group and the hydrosilane groups in the silicone elastomer. Here, for the first time, we report that solid state 13C nuclear magnetic resonance spectroscopy provides direct evidence for the irreversible binding of ethinyl estradiol – also a steroid molecule containing an ethynyl functional group – to an addition cure silicone elastomer. By preparing silicone elastomer samples containing 13C-labelled ethinyl estradiol, signals in the NMR spectra could readily be assigned to both the free and bound steroid. Additional depolymerisation studies, performed on an addition cure silicone elastomer system from which the unbound EE fraction was completely extracted, further confirmed the presence of bound EE through the formation of coloured reaction mixtures resulting from the reaction of bound EE and trifluoroacetic acid. These methods will be particularly useful in the ongoing development of new steroid-releasing silicone elastomer drug delivery devices, including various vaginal ring devices for contraception, HIV prevention and multipurpose prevention technology applications.
Original languageEnglish
Article number10.1016/j.ijpharm.2018.07.040
Pages (from-to)689-697
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume548
Early online date20 Jul 2018
DOIs
Publication statusEarly online date - 20 Jul 2018

Keywords

  • Covalent Binding
  • 17α-ethynyl-estradiol
  • 13C-labelled
  • Addition-cure silicone elastomer
  • Nuclear Magnetic Resonance
  • Hydrosilylation
  • Ethynyl group

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