Optimization of dissolution test precision for a ketoprofen oral extended-release product.

An example of application of experimental design methodologies to the set up of dissolution test conditions for a new ketoprofen oral extended-release dosage form is presented. The aim of the work was to find the best experimental conditions, using a USP apparatus 2 (paddle), for maximizing the method precision as degree of repeatability. The considered factors mainly influencing the dissolution test results were pH and volume of dissolution medium, and paddle stirring speed. Two distinct 4-run Plackett-Burman designs were carried out: one at gastric and the other at intestinal pH values. Each run was performed in triplicate in order to calculate the standard deviations of the drug dissolution efficiency at 60 and 120 min, selected as responses to be minimized. Optimum conditions to carry out the dissolution test were: 900 ml volume of dissolution medium and 70 rpm paddle stirring speed for both environments and pH 1 and 5.5, for the gastric and intestinal environment, respectively.