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 antiretroviral agents dapivirine and tenofovir to prevent the 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 are mechanically comparable to the widely accepted NuvaRing IVR. Physical characterization of the individual IVR segments using wide angle X-ray scattering and differential scanning calorimetry determined that dapivirine and tenofovir are 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 are 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
Todd J
TJ
Department of Bioengineering, University of Utah, 20 S 2030 E, Salt Lake City, UT 84112, USA.
Gupta
Kavita M
KM
Fabian
Judit
J
Albright
Theodore H
TH
Kiser
Patrick F
PF
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000737:chemistry; D019245:Compressive Strength; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods*; D063065:Organophosphonates / Q000008:administration & dosage* / Q000737:chemistry; D011140:Polyurethanes / Q000008:administration & dosage* / Q000737:chemistry; D011743:Pyrimidines / Q000008:administration & dosage* / Q000737:chemistry; D000068698:Tenofovir
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D063065:Organophosphonates; D011140:Polyurethanes; D011743:Pyrimidines; D000068698:Tenofovir; D000225:Adenine; C481671:Dapivirine