Quantitative evaluation of a hydrophilic matrix intravaginal ring for the sustained delivery of tenofovir

J Control Release. 2012 Oct 28;163(2):240-8. doi: 10.1016/j.jconrel.2012.08.033. Epub 2012 Sep 7.


In vitro testing and quantitative analysis of a matrix, hydrophilic polyether urethane (HPEU) intravaginal ring (IVR) for sustained delivery of the anti-HIV agent tenofovir (TFV) are described. To aid in device design, we employed a pseudo-steady-state diffusion model to describe drug release, as well as an elastic mechanical model for ring compression to predict mechanical properties. TFV-HPEU IVRs of varying sizes and drug loadings were fabricated by hot-melt extrusion and injection molding. In vitro release rates of TFV were measured at 37 °C and pH 4.2 for 30 or 90 days, during which times IVR mechanical properties and swelling kinetics were monitored. Experimental data for drug release and mechanical properties were compared to model predictions. IVRs loaded with 21% TFV (w/w) released greater than 2mg TFV per day for 90 days. The diffusion model predicted 90 day release data by extrapolating forward from the first 7 days of data. Mechanical properties of IVRs were similar to NuvaRing, although the matrix elastic modulus decreased up to three-fold following hydration. This is the first vaginal dosage form to provide sustained delivery of milligram quantities of TFV for 90 days. Drug release and mechanical properties were approximated by analytical models, which may prove useful for the continuing development of IVRs for HIV prevention or other women's health indications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / chemistry
  • Administration, Intravaginal
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / chemistry*
  • Drug Delivery Systems*
  • Hydrophobic and Hydrophilic Interactions
  • Models, Theoretical*
  • Organophosphonates / administration & dosage
  • Organophosphonates / chemistry*
  • Polyurethanes
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / chemistry*
  • Tenofovir


  • Anti-HIV Agents
  • Organophosphonates
  • Polyurethanes
  • Reverse Transcriptase Inhibitors
  • polyetherurethane
  • Tenofovir
  • Adenine