Article

Pharmaceutical Research

, Volume 15, Issue 6, pp 889-896

First online:

In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2

  • Vinod P. ShahAffiliated withOffice of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration
  • , Yi TsongAffiliated withDivision of Biometrics III, Office of Epidemiology and Biometrics, Center for Drug Evaluation and Research, Food and Drug Administration
  • , Pradeep SatheAffiliated withOffice of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration
  • , Jen-Pei LiuAffiliated withDepartment of Statistics, National Cheng-Kung University

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Abstract

Purpose. To describe the properties of the similarity factor (f2) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means.

Methods. The f2 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. f2 values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f2 could be made using 90% confidence interval approach. 3. The statistical distribution of f2 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 f2 is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate ^f2 is a biased and conservative estimate of f2. The bootstrap approach is a useful tool to simulate the confidence interval.

dissolution similarity factor estimation bias bootstrap confidence interval