Perturbation study of dissolution apparatus variables—A design of experiment approach

Abstract

The specifications and acceptable ranges for nine critical dissolution apparatus variables were examined during a perturbation study of USP dissolution Apparatus 2 using USP Prednisone Reference Standard (RS) Tablets. A Design of Experiment (1) approach was used to screen the nine variables to determine the contribution of each, alone and in combination, to mean percent dissolved and standard deviation results. We observed a wide range of dissolution results, including several values that fell outside of current acceptance limits, even though the variables were kept within currently acceptable ranges. When we analyzed mean percent dissolved results, we found three variables that were statistically significant: level of deaeration, vessel type, and rotation speed. When we examined standard deviation results, we found that five variables or combinations of variables were statistically significant: vessel type, level of deaeration, paddle height, paddle height–vessel type interaction, and paddle height–level of deaeration interaction. We also found that the other variables examined—temperature, shaft wobble, vessel centering,vessel tilt, and base plate levelness—were not statistically significant within the ranges explored in this study. Acceptance ranges for several assembly variables may need to be more stringent or more precisely defined in order to decrease inter- and intralaboratory variability (reproducibility and repeatability) in dissolution testing.