In vitro dissolution profile comparison -: Statistics and analysis of the similarity factor, f2

Purpose. To describe the properties of the similarity factor (f(2)) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means. Methods. The f(2) metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculated using bootstrapping method. The bias of the estimate using sample mean dissolution is evaluated. Results. 1. f(2) values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f(2) could be made using 90% confidence interval approach. 3. The statistical distribution of f(2) metrics could be simulated using 'Bootstrap' method. A relatively robust distribution could be obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was found to reduce the bias. Conclusions. The similarity factor f(2) is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate (f) over cap(2) is a biased and conservative estimate of f(2). The bootstrap approach is a useful tool to simulate the confidence interval.