Point and Interval Estimation of Drug Dissolution Similarity Factor (f2)
Keywords:
Bootstrap Percentile (BP), dissolution profile similarity, point and interval estimate, similarity factor (f2)Abstract
Abstract. Comparative dissolution testing is conducted during drug development to compare the dissolution profiles of a test product and a reference product. The similarity between these two dissolution profiles is commonly evaluated using the similarity factor (f2). However, the f2 value provides only a point estimate and does not provide information about the uncertainty associated with the estimate. Therefore, the objective of this paper is to determine the point estimate of similarity factor (f2) as well as its interval estimate using nonparametric Bootstrap Percentile (BP) method. The methods were applied to evaluate the similarity profiles of dissolution percentages between 12 tablets of the test product (AB 80 mg) and 12 tablets of the reference product (AB 100 mg) measured at six sampling time points of 10, 15, 30, 45, 60, and 90 minutes. The first step was calculating the f2 value as a point estimate, followed by the development of interval estimate using nonparametric Bootstrap Percentile with 1000 replications. The resulted point estimate of f2 was 56.6326, indicating that the dissolution profiles was similar. The interval estimate with 90% confidence was (52.5015, 61.0991). Since the lower confidence limit is greater than 50, the dissolution profiles of the test product and the reference product are considered similar. The findings indicate that the BP method provides a confidence interval for the similarity factor (f2), allowing estimation uncertainty to be incorporated into the evaluation of dissolution profile similarity. Both point and interval estimates indicate that the test product and the reference product have similar dissolution profiles.
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