Comparison of in-vitro release rates for vaginal systems.

Vaginal systems (VSs) or intravaginal rings are flexible, polymer-based, drug-device delivery systems used for release of one or more drugs directly to the vaginal-cervical tissues for an extended period. These complex products can undergo chemistry, manufacturing, and controls (CMC) changes. Comparative in-vitro release testing between prechange and postchange product can be used to support minor/moderate CMC changes. Due to long drug release period, the cumulative profile may be insensitive to visualize release rates' trend over time. Any summary statistic, e.g. the similarity factor f2 for dissolution profiles' comparison, may hide a large deviation at some time points since a summary statistic is equivalent to comparing the mean difference between two profiles averaged over time. This is problematic since the amount released per day is critical to ensure maintaining product quality and product performance consistently. Therefore, a summary statistic does not fit for the use. Another way to compare two profiles is to compare the estimated parameters after fitting the data to a curve which can be described by a few parameters. However, due to irregularity of these curves with limited number of time points, modeling approach, resulting in a large deviation at some points, isn't practical. In addition, specifications on in-vitro release rates of drug product at several pre-selected time points are generally recommended when a batch is released to the market and through the stability. We propose an equivalence testing approach for comparing in-vitro release rates between the prechange and the postchange VS at each of preselected time points.