The Effect of Fill Level on the Granule Size Distribution in a High Shear Granulator

Abstract

Corn starch powders are commonly used in pharmaceutical industries as drug fillers. In this work, corn starch powders with the mean diameter of 15.6μm are granulated in a laboratory scale high shear granulator with the capacity of 1 L. Before granulation, the corn starch powders are stored in a controlled environment of 25oC and relative humidity of 65% for 24 hr. The methocel aqueous solution of 1750 cp is used as the binder solution. The angle of the three-bladed impeller is 45° and the three blades are 120o apart. The blade is 16.5 mm in height and 47.2 mm in length. In a typical experiment, the corn starch powders 55.5 g, 88.8 g , 111.0 g or 154.1 g, which corresponds to the dimensionless fill level w.r.t. the blade height of 0.5, 0.8, 1 and 1.5, respectively, are pulled into the bowl and levelled. The powder-to-binder mass ratio is fixed at 2.26 in all experimental runs. The entire binder solution is sprayed onto the corn starch powders at vigorous mixing through a nozzle within 1 min. The impeller spins at 500 rpm and the chopper rotates at 1500rpm in all cases. After 3 min or 4 min granulation time, the granules are gently removed from the bowl through a bottom chute. The wet granules are oven-dried at 70oC for 24 hr and sieved into 15 size categories. The influences of the initial powder fill level and granulation time on the granule size distribution are investigated. Figure 1 shows the influences of the granulation time on the granule size distribution. The granulation time has a more pronounced influence on the granule size distribution at high fill levels than that at low fill levels in the range studied. Increasing the granulation time from 3 min to 4 min, there are more chances for the granules to coalesce, to compact and to fracture. At high fill levels, more granules participate these events and hence a broader granule size distribution is obtained at high fill levels after a longer granulation time. Figure 2 shows that the mass mean granule particle size increases with the increasing of the fill level and a longer granulation time leads to a larger mean granule size. Increasing the fill level allows more powders to be involved in the granulation process and hence produces larger granules after the coalescence events. However, since the blade height is fixed at 16.5 mm in all experimental runs, not all powders in the vessel are involved in the bladed-strike granule coalescence events at the highest fill levels of 1.5, the increasing of the mean granule size is limited in this case.