Impact of mechanical calibration variations on USP prednisone PVT with standard and apex vessels†

Abstract

Dissolution testing is a method to assess the impact of pharmaceutical formulation and bioequivalence between comparator drugs, among other uses. The dissolution paddle tester (USP Apparatus 2) has been widely used by industry to evaluate the rate of a drug's dissolution from a formulation. The United States Pharmacopeia (USP) issued a new Dissolution Performance Verification Standard (DPVS) – Prednisone Reference Standard in 2023, along with a new set of Performance Verification Test (PVT) criteria to be performed in addition to mechanical calibration for instrument qualification. Apex vessels are dissolution vessels with a convex bottom that have gained interest due to improved hydrodynamics and reduced accumulation of trapped drug product in formulation at the bottom of the vessel during dissolution testing. In this study, we evaluated the effect of changing mechanical calibration parameters within the acceptable mechanical calibration ranges and their impacts on the dissolution of the new DPVS – Prednisone tablets in deaerated water using both standard and apex vessels as well as whether the test results from varied apparatus configurations met the PVT acceptance criteria. All configurations within specified parameters for standard vessels fell within PVT acceptance criteria, but the higher dissolution rate in apex vessels fell beyond the current PVT acceptance range. This indicates that the current PVT or DPVS-Prednisone tablet is not suitable for the qualification of USP Apparatus 2 fitted with apex vessels.