Impact of ring size and drug loading on the pharmacokinetics of a combination dapivirine-darunavir vaginal ring in cynomolgus macaques

International Journal of Pharmaceutics
Diarmaid J MurphyR Karl Malcolm

Abstract

This work investigates the impact of vaginal ring size and drug loading on the in vitro release, safety, ease of fit, and pharmacokinetics in cynomolgus macaques of matrix-type silicone elastomer vaginal rings containing a combination of the non-nucleoside reverse transcriptase inhibitor dapivirine and the protease inhibitor darunavir. Drug-free and drug-loaded vaginal rings having three different geometries were manufactured by reaction injection molding. In vitro drug release was assessed using both a solvent/water mixture and a vaginal fluid simulant. Macaques fitted with drug-free vaginal rings for 28 days were assessed by colposcopy, cytological evaluation of cervico-vaginal lavage and histological evaluation of tissue after ring removal. The 20 × 4.5 mm combination ring, deemed most appropriate for vaginal fit and comfort in the macaques, was evaluated for pharmacokinetics over 28 days. Substantial differences were observed in the in vitro release profiles between the three ring sizes. However, these differences were not manifest in vivo, where measured drug concentrations after 20 × 4.5 mm ring use were not significantly different from those reported previously with a 25 × 6 mm ring. These results suggest that ring place...Continue Reading

Citations

Apr 24, 2019·Pharmaceuticals·Kamal SinghAnders Sönnerborg
Oct 20, 2020·Advanced Materials Technologies·Rima JanusziewiczS Rahima Benhabbour
Feb 2, 2021·International Journal of Pharmaceutics·Mattia TiboniLuca Casettari
Jul 20, 2021·Geburtshilfe und Frauenheilkunde·Fojan RafieiKhosrow Mottaghy
Aug 28, 2021·International Journal of Pharmaceutics·Raúl Cazorla-LunaDimitrios A Lamprou
Jan 13, 2022·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Ignacio Rodríguez-IzquierdoMa Ángeles Muñoz-Fernández

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