The Use of Statistical Moment Analysis to Elucidate the Mechanism of Release of a Model Drug from Pellets Produced by Extrusion and Spheronisation.

Abstract

The dissolution profile of a model drug (indomethacin) in pellets produced by extrusion and spheronisation has been evaluated according to the method described in the USP XXIII, apparatus II. The effects of the speed of the paddles, temperature, pH and size of the pellets, i.e., the surface area have been examined. The study was complemented by coating the pellets with a polymer (ethylcellulose) in an aqueous dispersion and changes in the release of the drug were monitored. The analysis of the results was carried out by determination of two statistical moments mean dissolution time (MDT) of indomethacin and variance of dissolution time (VR) and an associated parameter, the relative dispersion of the concentration-time profile (RD). From these parameters, it was possible to relate the release of the drug to the dissolution mechanisms and models described in the literature. The present study has shown the possibility of analysing the complete release of the indomethacin as opposed to the traditional approach of considering only 40-60% of the drug released. The analysis has also shown that the mechanism of release of the drug changes throughout the test. Finally, for pellets coated with ethylcellulose, the coating altered the rate of release of the drug and changes in the release mechanism were also observed. Under certain conditions a zero order release rate was obtained.