Novel metrics to compare dissolution profiles.
OBJECTIVE
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 (rho, rho m, delta a, and delta s), along with f2, were applied to dissolution data from FAST and SLOW metoprolol tartrate tablets. For example, rho m is defined as: [formula: see text] 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 rho, rho m, delta a, delta 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 rho, rho m, delta a, and delta 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 rho, rho m, delta a, delta 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 rho, rho m, delta a, and delta s appear to be viable methods to compare dissolution profiles, particularly rho m.
Seo
Paul R
PR
Department of Pharmaceutical Sciences, School of Pharmacy, 20 North Pine Street, University of Maryland, Baltimore, MD 21201, USA.
Shah
Vinod P
VP
Polli
James E
JE
D008433:Mathematics; D008790:Metoprolol / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility
D008790:Metoprolol