The Effect of Particle Size on Some In-Vitro and In-Vivo Properties of Indomethacin-Polyethylene Glycol 6000 Solid Dispersions

Abstract

Drug release from indomethacin-polyethylene glycol solid dispersions has been examined using three different size fractions. Release rates at a stirring rate of 100 rpm were generally higher from the 250-375 micron fraction than from particles in the ranges 125-188 and 500-750 microns. Release rates were highest from dispersions containing 5% indomethacin and showed a 240-fold increase at 100 rpm and a 1200-fold increase at 50 rpm over those at the same stirring rate of indomethacin alone (125-188 microns). As the percentage of indomethacin in the dispersions increased (5 to 40%) the dissolution rates decreased and for dispersions containing .15% indomethacin, complete solution of the drug was not achieved within 2 hours. The 500-750 micron fraction of the dispersion containing 10% indomethacin was significantly more gastro-toxic than particles of 125-188 microns.