Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir.
Dual segment polyurethane intravaginal rings (IVRs) were fabricated to enable sustained release of the antiretroviral agents dapivirine and tenofovir to prevent male to female sexual transmission of the human immunodeficiency virus. Due to the contrasting hydrophilicity of the two drugs, dapivirine and tenofovir were separately formulated into polymers with matching hydrophilicity via solvent casting and hot melt extrusion. The resultant drug-loaded rods were then joined together to form dual segment IVRs. Compression testing of the IVRs revealed that they were mechanically comparable to the widely accepted NuvaRing<sup>®</sup> IVR. Physical characterization of the individual IVR segments using wide angle X-ray scattering and differential scanning calorimetry determined that dapivirine and tenofovir were amorphous and crystalline within their polymeric segments, respectively. In vitro release of tenofovir from the dual segment IVR was sustained over 30 days while dapivirine exhibited linear release over the time period. A 90-day accelerated stability study confirmed that dapivirine and tenofovir were stable in the IVR formulation. Altogether, these results suggest that multisegment polyurethane IVRs are an attractive formulation for the sustained vaginal delivery of drugs with contrasting hydrophilicity such as dapivirine and tenofovir.
Johnson, T.J.; Gupta, K.M.; Fabian, J.; Albrights, T.H.; Kiser, P.F. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. European Journal of Pharmaceutical Sciences (2010) 39 (4) 203-212. [DOI: 10.1016/j.ejps.2009.11.007]