Feasibility Study on Qualification of USP Dissolution Apparatus 1 and 2 Using the Enhanced Mechanical Calibration Procedure

Abstract

A feasibility study was conducted in an analytical laboratory to evaluate implementation of the alternative procedure proposed by the FDA for enhanced mechanical calibration of USP dissolution Apparatus 1 and 2. The investigation started with a historical review of qualification data for more than 50 systems, generated through our current practice of combining USP mechanical calibration with the USP Performance Verification Test (PVT) using prednisone tablets. The data were compared with the more comprehensive FDA procedures and more stringent criteria for enhanced mechanical calibration. All the historical results met both USP and FDA criteria for shaft wobble, basket wobble, basket/paddle height check, and rotational speed and, in addition, passed the USP PVT. Shaft verticality was the mechanical parameter that infrequently did not meet the enhanced calibration criterion. Further investigations were conducted on a few representative dissolution systems to examine shaft verticality and determine what factors affect it. System levelness greatly affected whether shaft verticality met the tolerance. It is concluded from the results of the evaluation that it may be difficult for certain older units to consistently meet the criteria for shaft verticality. Therefore, our plan is to continue the current practice of a combination of USP mechanical calibration with PVT and to monitor shaft verticality data.

Assessing the Impact of Vessel Centering on Dissolution Results–A Case Study

“…Of these instrument parameters, vessel/shaft centering is one of the most sensitive to vessel variability and is tightly controlled. Although there have been studies to evaluate the effect of apparatus variables on drug release (6)(7)(8)(9)(10), the impact specifically related to different centering values on dissolution results is still unknown. To evaluate the critical tolerance range around the ASTM centering value of 1.0 mm and the impact of off-centered vessels on drug release, experiments were carried out by manually adjusting the vessels to various off-centered conditions that were confirmed with an Agilent Q280 Mechanical Qualification System.…”