Progesterone-releasing vaginal rings for use in postpartum contraception. II. Pharmacokinetic profiles in women

In vitro release testing methods for drug-releasing vaginal rings

“…The sponsor subsequently changed the batch size, the manufacturing process, and the amount of noncontrolling excipients. Although these changes would normally require a bioequivalence study, the IVIVC was deemed acceptable and the changes were approved[137].As part of study to develop a 90-day progesterone-releasing vaginal ring for use in postpartum contraception, Landgren et al have reported a direct correlation between plasma progesterone levels (areas under curves) and in vitro release rates for rings offering three different initial release rates (5, 8 and 20 mg/day)[158]. In a follow-on clinical study, significantly higher concentrations of pregnanediol glucuronide -a major progesterone metabolite excreted in the urine -were measured for the 20 mg/day ring compared to the 5 mg/day ring[159].Clark et al makes reference to poor IVIVC in preliminary pharmacokinetic studies testing a UC781-loaded silicone elastomer matrix-type ring in pig-tailed macaques[160].However, the actual data was never published.…”