In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2
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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.
- FDA Guidance for Industry: Immediate Release Solid Dosage Forms: Scale-up and Post Approval Changes (SUPAC-IR): Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation, November, 1995.
- FDA Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, August, 1997.
- FDA Guidance for Industry: Extended Release Oral Dosage Forms: Development, Evaluation and Application of In Vitro/In Vivo Correlations, September, 1997.
- FDA Guidance for Industry: Modified Release Solid Oral Dosage Forms: Scale-Up and Post Approval Changes (SUPAC-MR): Chemistry, Manufacturing and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation, September, 1997.
- V. P. Shah, L. A. Yamamoto, D. Shuirmann, J. Elkins, and J. P. Skelly. Analysis of in vitro dissolution of whole versus half controlled release theophylline tablets. Pharm. Res. 4:416-419 (1987).
- S. C. Chow and F. Y. C. Ki. Statistical comparison between dissolution profiles of drug products. J. Biopharm. Stat. 7:241-258 (1997).
- P. Sathe, Y. Tsong, and V. P. Shah. In-vitro dissolution profile comparison: statistics and analysis, model dependent approach. Pharm. Res. 13:1799-1803 (1996).
- Y. Tsong, T. Hammerstrom, P. Sathe, and V. P. Shah. Statistical assessment of mean difference between two dissolution data sets. Drug Inf. J. 30:1105-1112 (1996).
- J. W. Moore and H. H. Flanner. Mathematical comparison of curves with an emphasis on in-vitro dissolution profiles. Pharm. Tech. 20(6):64-74 (1996).
- J. E. Polli, G. S. Rekhi, and V. P. Shah. Methods to compare dissolution profiles. Drug Info. J. 30:1113-1120 (1996).
- J. E. Polli, G. S. Rekhi, L. L. Augsburger, and V. P. Shah. Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets. J. Pharm. Sci. 86:690-700 (1997).
- J. P. Liu, M. C. Ma, and S. C. Chow. Statistical evaluation of similarity factor f2 as a criterion for assessment of similarity between dissolution profiles. Drug Info. J. 31:1255-1271 (1997).
- H. L. Ju and Liaw S. On the assessment of similarity of drug dissolution profile—a simulation study. Drug Info. J. 31:1273-1289 (1997).
- R. A. Johnson and D. W. Wichern. Applied Multivariate Statistical Analysis, Prentice-Hall, Inc. Englewood Cliffs, NJ, 1982.
- Y. Tsong, P. Sathe, and V. P. Shah. Comparing two dissolution data sets for similarity, American Statistical Association. 1996 Proceedings of the Biopharmaceutical Section, 129-134, 1997.
- B. Efron and R. J. Tibshirani. An Introduction to the Bootstrap, Chapman & Hall, New York, NY, 1993.
- In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2
Volume 15, Issue 6 , pp 889-896
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- Kluwer Academic Publishers-Plenum Publishers
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- similarity factor
- estimation bias
- bootstrap confidence interval
- Industry Sectors
- Author Affiliations
- 1. Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, HFD-350,1451, Rockville Pike, WOC 2, Rockville, Maryland, 20852
- 2. Division of Biometrics III, Office of Epidemiology and Biometrics, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, 20857
- 3. Department of Statistics, National Cheng-Kung University, Tainan, Taiwan, ROC