A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action

Susan M. Fetherston, Peter Boyd, Clare F. McCoy, Marcella C. McBride, Karen-Leigh Edwards, Stephen Ampofo, R. Karl Malcolm

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)
98 Downloads (Pure)

Abstract

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25 mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25 mg dapivirine and various quantities of maraviroc (50– 400 mg) were manufactured and in vitro release assessed. The 25 mg dapivirine and 100 mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.
Original languageEnglish
Pages (from-to)406-415
Number of pages10
JournalEuropean journal of pharmaceutical sciences
Volume48
Issue number3
Early online date21 Dec 2012
DOIs
Publication statusPublished - 14 Feb 2013

Keywords

  • Controlled release, HIV microbicide, dapivirine, maraviroc, vaginal ring

ASJC Scopus subject areas

  • Behavioral Neuroscience

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