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, ρm, δa, and δs), along with f2, were applied to dissolution data from FAST and SLOW metoprolol tartrate tablets. For example, ρm is defined as:where Rt is the percent dissolved of the reference product at time t, Tt the percent dissolved of the test product at time t, and RATIOt the larger of either Rt/Tt or Tt/Rt. 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, ρm, δa, δs, 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, ρm, δa, and δs 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, ρm, δa, δs, 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, ρm, δa, and δs appear to be viable methods to compare dissolution profiles, particularly ρm.