Implementation of Pharmaceutical Quality by Design in Wet Granulation

Abstract In this chapter, we demonstrate our effort to develop and utilize a unit operation profile to help better implement the Quality by Design (QbD) paradigm in unit operation development. A unit operation profile can be created by collecting, aligning, and standardizing the drug substance's information, formulation information, and process information related to the specific unit operation from scientific documents within the same data structure. Here, profiles of fluidized bed (FB) granulation and high-shear/low-shear (HS/LS) granulation were created based on recently approved drug product applications available at agency. Based on these two profiles, we present the general operation procedures for high-shear/low-shear granulation and fluidized bed granulation, discuss the popularity of process outputs to characterize the granulation quality, quantify the importance of process parameters, and the research pattern of these parameters, identify material attributes that could interact with process parameters, and discuss the utilization of QbD tools (Risk Assessment, Design of Experiment, and Process Analytical Technology) in process development of wet granulation.