IN-VITRO DISSOLUTION PROFILE COMPARISON - STATISTICS AND ANALYSIS OF THE SIMILARITY FACTOR, F(2)

Purpose. To describe the properties of the similarity factor (f(2)) as a measure for assessing the similarity of two dissolution profiles. D iscuss the statistical properties of the estimate based on sample mean s. Methods. The f(2) metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculate d using bootstrapping method. The bias of the estimate using sample me an dissolution is evaluated. Results. 1. f(2) values were found to be sensitive to number of sample points, after the dissolution plateau ha s been reached. 2. The statistical evaluation of f(2) could be made us ing 90% confidence interval approach. 3. The statistical distribution of f(2) metrics could be simulated using 'Bootstrap' method. A relativ ely robust distribution could be obtained after more than 500 'Bootstr aps'. 4. A statistical 'bias correction' was found to reduce the bias. Conclusions. The similarity factor f(2) is a simple measure for the c omparison of two dissolution profiles. But the commonly used similarit y factor estimate (f) over cap(2) is a biased and conservative estimat e of f(2). The bootstrap approach is a useful tool to simulate the con fidence interval.