Long-term, controlled release of the HIV microbicide TMC120 from silicone elastomer vaginal rings

J Antimicrob Chemother. 2005 Nov;56(5):954-6. doi: 10.1093/jac/dki326. Epub 2005 Sep 9.

Abstract

Objectives: The feasibility of providing prolonged and controlled release of the experimental non-nucleoside reverse transcriptase inhibitor TMC120 from a silicone vaginal ring in quantities sufficient to maintain a vaginal concentration offering protection against heterosexual HIV transmission was investigated.

Methods: Core-type, silicone elastomer vaginal rings containing TMC120 were manufactured, and in vitro release studies performed under sink conditions. The experimental release data, as determined by HPLC, were correlated with estimates of vaginal TMC120 concentrations required to inhibit HIV replication.

Results: Continuous, zero-order release of TMC120 from core-type vaginal rings was observed in vitro over a 71 day period, equivalent to 136 microg/day. The release rate is predicted to maintain vaginal concentrations of the antiretroviral in the range of several orders of magnitude in excess of reported HIV inhibitory concentration values.

Conclusions: Continuous and prolonged zero-order release of TMC120 from a silicone vaginal ring device at quantities predicted to prevent HIV infection was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / analysis
  • Anti-HIV Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Contraceptive Devices, Female*
  • Delayed-Action Preparations
  • HIV Infections / prevention & control*
  • Humans
  • Pyrimidines / administration & dosage*
  • Pyrimidines / analysis
  • Pyrimidines / pharmacokinetics*
  • Sexually Transmitted Diseases, Viral / prevention & control*
  • Silicone Elastomers

Substances

  • Anti-HIV Agents
  • Delayed-Action Preparations
  • Pyrimidines
  • Silicone Elastomers
  • Dapivirine