Investigation of the effect of impeller speed on granules formed using a PMA-1 high shear granulator

Impeller speed was varied from 300 to 1500 rpm during the wet high shear granulation of a placebo formulation using a new vertical shaft PharmaMATRIX-1 granulator. The resulting granules were extensively analysed for differences caused by the varying impeller speed with emphasis on flowability. Microscopy showed that initial granules were formed primarily from microcrystalline cellulose at all tested impeller speeds. At low impeller speed of 300 rpm in the bumpy flow regime, forces from the impeller were insufficient to incorporate all the components of the formulation into the granules and to promote granule growth to a size that significantly improved flowability. The roping flow regime at higher impeller speeds promoted granule growth to a median particle size of at least 100 mu m that improved the flowability of the mixture. Particle size distribution measurements and advanced indicators based on avalanching behavior, however, showed that an impeller speed of 700 rpm produced the largest fraction of optimal granules with the best flowability potential. This impeller speed allowed good development of roping flow for sufficient mixing, collision rates and kinetic energy for collisions while minimizing excessive centrifugal forces that promote buildup around the bowl perimeter.