Simplified Model-Dependent and Model-Independent Approaches for Dissolution Profile Comparison for Oral Products: Regulatory Perspective for Generic Product Development

Discriminative Dissolution Method Using the Open-Loop Configuration of the USP IV Apparatus to Compare Dissolution Profiles of Metoprolol Tartrate Immediate-Release Tablets: Use of Kinetic Parameters

“…Although it has been reported that model-dependent approaches with a single parameter, such as those used above, can be subject to MSD analysis to establish similarities in dissolution profiles with high variability [ 11 , 15 ], the drawback was that the dissolution profiles obtained in both dissolution apparatuses of generic drugs “B” and “C” could not be compared since they were adjusted to different models compared to the reference drug “A”.…”

“…Subsequently, the global similarity limits were established based on the average dissolved percentages of the reference drug with a tolerance of ±10% for MD (DM10%), followed by the similarity limits, which were calculated using the global similarity limits to establish the upper limit at a 90% confidence level for the true MD. The similarity in the dissolution profiles was considered when DM was less than the DM10% limit [ 11 , 21 ]. In contrast, when the variance–covariance matrix was not symmetric (heterogeneous), the method to evaluate the similarity of the dissolution profiles was through Hotelling’s T 2 statistic (global similarity) and considering their 90% confidence intervals for each sampling time (local similarity) [ 22 ].…”

“…The comparison of the dissolution profiles obtained in both dissolution apparatus considering these methods consisted in the estimation of the 90% confidence region limits of their α (scale factor) and β (shape factor) parameters (log-transformed) and the region of similarity, which considered 2 standard deviations (2 STD) for the reference product, that is, approximately 95% confidence [ 15 , 19 , 27 ]. Dissolution profiles were considered similar if the 90% confidence region limits for each model parameter were included in the region of similarity [ 11 ].…”

“…These comparison methods consist of three groups: the methods based on analysis of variance (ANOVA), model-dependent methods, and model-independent methods, but the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) guidelines on bioequivalence prefer the model-independent method based on the calculation of the similarity factor ( f 2 ) when the variability of the dissolution profiles complies with what is established in the guidelines [ 10 ]. However, when the variability in the dissolution profiles is high, there is no single comparison method, since the EMA prefers to use the bootstrap f 2 approach and the FDA establishes the use of multivariate methods and dependent models, that is, still the comparison methods have not been homologated [ 1 , 11 ].…”

Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability

“…Mean values of continuous data were compared using an ANOVA test. Dissolution data were compared using a model-independent approach (i.e., f1 difference factor and f2 similarity factor) [ 37 ]. Mean values were compared using ANOVA (post hoc Tukey), differences were considered significant if p < 0.05.…”