A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781

Meredith R. Clark, Todd J. Johnson, R. Tyler McCabe, Justin T. Clark, Anthony Tuitupou, Hoda Elgendy, David R. Friend, Patrick F. Kiser*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Microbicide intravaginal rings (IVRs) are a promising woman-controlled strategy for preventing sexual transmission of human immunodeficiency virus (HIV). An IVR was prepared and developed from polyether urethane (PU) elastomers for the sustained delivery of UC781, a highly potent nonnucleoside reverse transcriptase inhibitor of HIV-1. PU IVRs containing UC781 were fabricated using a hot-melt extrusion process. In vitro release studies of UC781 demonstrated that UC781 release profiles are loading dependent and resemble matrix-type, diffusion-limited kinetics. The in vitro release methods employed over predicted the in vivo release rates of UC781 in rabbits. Accelerated stability studies showed good chemical stability of UC781 in prototype formulations, but surface crystallization of UC781 was observed following long-term storage at higher UC781 loadings, unless formulated with a polyvinylpyrrolidone/glycerol surface coating. Mechanical stability testing of prototype rings showed moderate stiffening upon storage. The PU and UC781 had minimal to no impact on viability, tissue integrity, barrier function, or cytokine expression in the tissue irritation model, and UC781 was shown to be delivered to and permeate through this tissue construct in vitro. Overall, UC781 was formulated in a stable PU IVR and provided controlled release of UC781 both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)576-587
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume101
Issue number2
DOIs
StatePublished - Jan 1 2012

Keywords

  • Controlled release
  • Extrusion
  • In vitro/in vivo release
  • Intravaginal ring
  • Microbicides
  • Mucosal drug delivery, polymeric drug delivery system, extrusion, stability
  • Polymeric drug delivery system
  • Polyurethane
  • Stability
  • UC781

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Clark, M. R., Johnson, T. J., McCabe, R. T., Clark, J. T., Tuitupou, A., Elgendy, H., Friend, D. R., & Kiser, P. F. (2012). A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781. Journal of Pharmaceutical Sciences, 101(2), 576-587. https://doi.org/10.1002/jps.22781