Guidelines on Dissolution Profile Comparison

Abstract

This article presents a short review on guidelines for dissolution profile testing, particularly focusing on the recommendations regarding statistical methods for assessing profile similarity. In this context, the guidelines on in vitroh vivo correlations and on granting biowaivers are outlined briefly. The comparison of two dissolution profiles can be performed in different ways. There are many model-dependent and model-independent procedures suggested in the methodical literature. Current guidelines primarily recommend the application of a method based upon the f2 statistic as a measure of the similarity of two dissolution curves, though this procedure has often been criticized recently. The goal of this article is to give a survey of the current guidelines, including a description and discussion of the recommended methods for data analysis.

Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations?

“…According to the guidelines issued by the 14 regulatory authorities evaluated in this study, f 1 values up to 15 (0-15) and f 2 values greater than 50 (50-100) ensure the Bsamenessô r Bequivalence^of the two profiles (1,2). Values less than 50 may be acceptable if justified (5,14).…”

“…This approach is favored because it is relatively easy to use, the f 2 value is easy to calculate, and a clear acceptance criterion for profile similarity (i.e., f 2 ≥50) has been established (2). An f 2 value of 50 corresponds to an average difference of 10% at all specified time points (3).…”

“…While the majority of the published literature focuses on the f 2 requirements in major markets (2,(7)(8)(9)(10), there exists limited literature comparing other global markets. Each country determines how to apply and enforce regulations to ensure the safety and efficacy of pharmaceutical products for sale in their jurisdiction, and the regulatory authorities in these markets are asking for more information about dissolution methods and dissolution profile comparisons.…”

“…The resulting dissolution profiles of the product or products under different test conditions (e.g., media pH) can then be compared using model-independent or modeldependent methods (2). The model-independent similarity factor (f 2 ) approach is a relatively simple and widely accepted method for comparing dissolution profiles.…”

Development and Validation of a Discriminative Dissolution Method for Atorvastatin Calcium Tablets using in vivo Data by LC and UV Methods

“…The dissolution profiles obtained for the RP, PA, and PB were compared by the model-independent approach, which includes the difference factor (f 1 ) and the similarity factor (f 2 ) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”