Novel Metrics to Compare Dissolution Profiles

Abstract

Purpose: To evaluate four novel metrics that compare dissolution profiles and assess their performance characteristics by comparing dissolution profiles of FAST and SLOW immediate release metoprolol tartrate tablets.

Methods:The four novel metrics (ρ, ρ_m, δ_a, and δ_s), along with f₂, were applied to dissolution data from FAST and SLOW metoprolol tartrate tablets. For example, ρ_m is defined as:where R_t is the percent dissolved of the reference product at time t, T_t the percent dissolved of the test product at time t, and RATIO_t the larger of either R_t/T_t or T_t/R_t. The mean metric values, upper (or lower) confidence limits, and skewness values were calculated, in order to characterize the performance of each metric.

Results: The mean values of ρ, ρ_m, δ_a, δ_s, and f₂ were 1.80, 0.80, 0.47, 0.36, and 19.6, respectively. The novel metrics indicate that greater than a 50% relative difference exists between the FAST and SLOW profiles. The upper 95% confidence limits for ρ, ρ_m, δ_a, and δ_s were 1.84, 0.83, 0.48, and 0.38, respectively, with f₂ having a lower limit of 19.1. Skewness values for ln-transformed ρ, ρ_m, δ_a, δ_s, and f₂ were 0.81, 0.71, 0.86, 0.47, and −0.94, respectively, suggesting favorable metric distribution properties.

Conclusions: The direct curve comparison metrics ρ, ρ_m, δ_a, and δ_s appear to be viable methods to compare dissolution profiles, particularly ρ_m.

Keywords:

• Dissolution
• Dissolution profile comparison
• Metoprolol tartrate
• Bioequivalence