Chapter 3 - Mechanistic Basis for the Effects of Process Parameters on Quality Attributes in High Shear Wet Granulation

Abstract

The mechanisms of the effect of process parameters on primary properties of granules manufactured by wet granulation (size and density), bulk performance indicating properties (flow, compaction properties), and final tablet quality attribute (dissolution) are discussed based on studies performed on active and placebo formulations. Water amount has significant effect on granule size and density. The effect of impeller speed is dependent on the granule mechanical properties and efficiency of liquid distribution in the granulator. Granule porosity decreases and blend density increases rapidly during the wet massing phase of high shear wet granulation. Liquid addition rate is the least consequential factor and generally has minimal impact on granule density and growth. Bulk powder properties (compaction and flow) and tablet dissolution usually are dependent on primary granule properties. The effects of the process parameters on the bulk powder properties and tablet dissolution are consistent with their link to primary granule properties. Understanding the impact of primary granule properties on bulk powder properties and final product critical quality attributes provides the basis for modulating granulation parameters in order to optimize product performance.