Material Attributes and Their Impact on Wet Granulation Process Performance

Abstract The wet granulation process is employed frequently during the manufacture of solid dosage forms to enhance the characteristics of active pharmaceutical ingredients (API) and their premix (dry blend) for processing into solid dosage units with the desired quality attributes. The purpose is to obtain homogeneous granules to improve the flow, content uniformity, compression characteristics, and drug release profile; and to reduce the potential for segregation and dusting (important for contamination and safety). Granules that possess ideal properties result in efficient processing and high throughput of solid dose units with desired critical quality attributes (CQAs), such as assay, weight, hardness, and disintegration. The properties of the granules, such as porosity, hygroscopicity, hardness, size, shape, texture, surface area, density, elasticity, and plasticity, can be controlled through manipulation of several processing parameters and material attributes. It is of paramount significance to understand how material attributes and process parameters/conditions influence the quality attributes of granules. This chapter attempts to evaluate the effect of excipient/raw-material properties (also called critical material attributes, or CMAs) on the critical quality attributes of granules produced by the wet granulation process. The common materials―diluents, binders, disintegrants, and lubricants―are emphasized here. Material properties, such as particle size, shape, bulk density, flowability, surface properties, water content, and composition, are discussed.