Evaluation of induced variance of physical parameters on the calibrated USP dissolution apparatus 1 and 2

Abstract

Although the test populations for these simple studies were relatively small,they have indicated whether induced variance has an affect on a seemingly sensitive pharmaceutical product, the USP 10-mg Prednisone dissolution calibrator tablet. While subtle variations in temperature did not seem to influence the behavior of the Prednisone dissolution rate,the influence of vibration could be minimal or dramatic, given the consideration of frequency. The various effects of vibration found in this study correlate with a previous finding summarized in a PhRMA dissolution calibrator study on enhanced mechanical calibration; that there is a need to generate additional data to study and understand the effects of vibration on dissolution results (5). However, the results of vibration testing herein clearly indicate that displacement may not be an appropriate term to quantitate the effects of vibration. The importance of validating individual dissolution methods to study the effects of modifications to established testing standards, as outlined in the USP, becomes startlingly evident when we see a 12% decrease in test results after changing a basket attachment device from clips to an unofficial O-ring design. In the interest of good science,data generated from unofficial O-ring baskets should not be used in USP Collaborative Studies for determining the limits for the USP Calibrator tablets. Incorporation of such data will skew data downward, lowering the upper control limit which may cause unnecessary failures in the field for calibrations performed with official clip-type basket attachment. Finally, as the mesh study indicates,the need for universal and consistent testing standards, although demanded by our global economy,should not obscure our obligation to produce consistent and comparable dissolution test results.