In vitro dissolution profile comparison--statistics and analysis of the similarity factor, f2.
ABSTRACT 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.
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.
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.
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.
- Pharmaceutical Technology 01/1996; 20(6):64-74.
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ABSTRACT: Controlled-release (CR) drug products dissolve more slowly than conventional-release products, reflecting their quality of sustaining a prolonged therapeutic effect. A frequent practice with scored tablets when only half the dosage is desired is to divide the tablet at the score mark and administer only half of the product. The dissolution characteristics of the divided tablets are unknown. It is only an assumption that the halved tablet behaves similarly to the whole tablet both in vitro and in vivo. A series of in vitro dissolution analyses was performed on whole and half CR theophylline tablets from different manufacturers. Statistical tests were carried out between the dissolution results of whole and those of halved tablets to determine whether the mean overall percentages dissolution (averaged over sampling times) were similar and whether the patterns of percentage dissolution over time were similar. The dissolution of halved tablets was slightly faster compared to that of intact (whole) tablets. However, these small differences were not large enough to cause concern or to require bioavailability studies.Pharmaceutical Research 11/1987; 4(5):416-9. · 4.74 Impact Factor
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ABSTRACT: When comparing the dissolution data of a postapproval change product and a reference approval product, the goal is to assess the similarity between the mean dissolution values at the observed sample time points. The decision on accepting or rejecting the hypothesis that the two batches have similar dissolution is based on the evidence regarding whether the difference in mean dissolution values between the test and reference products is no larger than the maximum expected difference between any two batches of the approval product. When dissolution value is measured at a single time point, the confidence interval of the true difference between the two batches is compared with the prespecified similarity limits. When dissolution values are measured at multiple time points, a multivariate statistical procedure for difference assessment can be a generalized form of the t-statistic procedure. The proposed procedure is a modification and generalization of the regular bioequivalence test concept. The application of the proposed multivariate analysis procedure is illustrated using an example.Drug Information Journal - DRUG INF J. 01/1996; 30(4):1105-1112.