A review of high shear wet granulation for better process understanding, control and product development

High shear wet granulation (HSWG) is considered a complicated and multivariate pharmaceutical process that is influenced by a large number of variables derived from equipment, formulations, and processes. A better understanding and effective control of the granulation process are required to achieve the desired attributes of the final target products and to improve the efficiency of product development. This review provides a comprehensive introduction to the improvement of HSWG-based product development, including the granulation mechanism, factors affecting the granulation process, in-line monitoring technologies, and modeling methods for HSWG process. We also discuss the application of quality by design in process control, especially its two important tools, risk management and design of experience. Additionally, some potential problems and challenges in current research are analyzed and highlighted. The main purpose is to provide comprehensive guidance for formulation scientists to better understand and control the HSWG process and then improve the product development.