Drug Release Testing of a Prostaglandin Containing Controlled-Release Vaginal Device: Development of a Semi-Automated Method

The effects of temperature, pH, and apparatus design on in vitro drug release from a controlled-release vaginal device containing the prostaglandin, carboprost methyl, were investigated and a semi-automated drug release test was developed based on these studies. Accelerated drug release testing was found not to be feasible due to an apparent change in the release mechanism observed at 60°C. At temperatures between 30–50°C, Arrhenius behavior was observed with an activation energy of 18 kcal/mol. Drug release from the device was found to be insensitive to changes in pH. A commercially available auto-sampler was modified to enable unattended sampling over a 24-h test period using a cumulative drug release test based on the USP apparatus 1. In vivo drug release from the devices was monitored by calculating the amount released in 24 h in vivo from the difference between initial drug content and residual drug content in devices returned from the clinic. Results obtained via the in vitro drug release test compare favorably with the in vivo release results.