Skip to main content
SpringerLink
Log in

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

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. 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.

  2. FDA Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, August, 1997.

  3. FDA Guidance for Industry: Extended Release Oral Dosage Forms: Development, Evaluation and Application of In Vitro/In Vivo Correlations, September, 1997.

  4. 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.

  5. 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).

    Google Scholar 

  6. S. C. Chow and F. Y. C. Ki. Statistical comparison between dissolution profiles of drug products. J. Biopharm. Stat. 7:241-258 (1997).

    Google Scholar 

  7. 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).

    Google Scholar 

  8. 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).

    Google Scholar 

  9. 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).

    Google Scholar 

  10. J. E. Polli, G. S. Rekhi, and V. P. Shah. Methods to compare dissolution profiles. Drug Info. J. 30:1113-1120 (1996).

    Google Scholar 

  11. 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).

    Google Scholar 

  12. 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).

    Google Scholar 

  13. 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).

    Google Scholar 

  14. R. A. Johnson and D. W. Wichern. Applied Multivariate Statistical Analysis, Prentice-Hall, Inc. Englewood Cliffs, NJ, 1982.

    Google Scholar 

  15. 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.

  16. B. Efron and R. J. Tibshirani. An Introduction to the Bootstrap, Chapman & Hall, New York, NY, 1993.

    Google Scholar 

Download references

Author information

Authors and 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

    Vinod P. Shah & Pradeep Sathe

  2. Division of Biometrics III, Office of Epidemiology and Biometrics, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, 20857

    Yi Tsong

  3. Department of Statistics, National Cheng-Kung University, Tainan, Taiwan, ROC

    Jen-Pei Liu

Authors
  1. Vinod P. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi Tsong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pradeep Sathe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jen-Pei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shah, V.P., Tsong, Y., Sathe, P. et al. In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2. Pharm Res 15, 889–896 (1998). https://doi.org/10.1023/A:1011976615750

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011976615750

Search

Navigation