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

Publication date: Available online 25 August 2018Source: International Journal of PharmaceuticsAuthor(s): Diarmaid J. Murphy, Delphine Desjardins, Peter Boyd, Nathalie Dereuddre- Bosquet, Lev Stimmer, Anna Caldwell, Roger Le Grand, Charles Kelly, Jens van Roey, R. Karl MalcolmAbstractThis 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 evaluted 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. The...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research