Statistical comparison of dissolution profiles

Abstract

Statistical methods to assess similarity of dissolution profiles are introduced. Sixteen groups of dissolution profiles from a full factorial design were used to demonstrate implementation details. Variables in the design include drug strength, tablet stability time, and dissolution testing condition. The 16 groups were considered similar when compared using the similarity factor f₂ (f₂ > 50). However, multivariate ANOVA (MANOVA) repeated measures suggested statistical differences. A modified principal component analysis (PCA) was used to describe the dissolution curves in terms of level and shape. The advantage of the modified PCA approach is that the calculated shape principal components will not be confounded by level effect. Effect size test using omega-squared was also used for dissolution comparisons. Effects indicated by omega-squared are independent of sample size and are a necessary supplement to p value reported from the MANOVA table. Methods to compare multiple groups show that product strength and dissolution testing condition had significant effects on both level and shape. For pairwise analysis, a post-hoc analysis using Tukey’s method categorized three similar groups, and was consistent with level-shape analysis. All these methods provide valuable information that is missed using f₂ method alone to compare average profiles. The improved statistical analysis approach introduced here enables one to better ascertain both statistical significance and clinical relevance, supporting more objective regulatory decisions.

• Dissolution profiles
• effect size
• f₂ factor
• multivariate data analysis
• principal component analysis
• statistical significance

Acknowledgements

This work is part of a research program in Engineering Research Center for Structured Organic Particulate Systems (CSOPS) at Rutgers University.

Declaration of interest

The authors report no conflicts of interest. The authors would like to thank Dr. German Drazer for his helpful discussions, and National Science Foundation (NSF/AIR Award# 1237873) for financial support.