Formation and internal microstructure of granules from wetting and non-wetting efavirenz/iron oxide blends

Abstract

An examination of granulation of non-wetting/wetting powder mixtures is presented. Non-wetting micron-size pharmaceutical active powder was blended with a sub-micron wetting excipient in three different ratios to produce wetting, non-wetting, and marginally-wetting powder blends. Model nuclei were prepared from these blends using binder droplets with viscosity of ca 10, 100 and 1000 mPa·s and further granulated in tumbling drum and high shear granulator. The effects of blend wettability, binder viscosity, granulation time, and shear forces on granule size and microstructure were investigated. Hollow granules were produced at higher binder viscosity of 100 and 1000 mPa·s regardless of blend wettability. Solid granules with a complex internal microstructure were produced at low binder viscosity of 10 mPa·s regardless of blend wettability. Contribution of capillary, viscous and impact forces are considered to explain differences in granule microstructure. Modified Reynolds and Weber numbers are proposed to rationalize formation and stability of shell microstructures.