Chapter 28 - Design, Development, and Scale-Up of the High-Shear Wet Granulation Process

Abstract

This chapter discusses the design, development, and scale-up aspects of the high-shear wet granulation process. In order to design a robust drug product and achieve the desired target product profile, it is important to have a good understanding of the critical material attributes (CMAs) and critical process parameters (CPPs) of the process and how these CMAs and CPPs are related to the drug product’s critical quality attributes. This chapter provides an overview of the CMAs (formulation-related) and CPPs (process-related) as they relate to high-shear wet granulation. In a quality by design paradigm, there is a need to establish both formulation and process design space, which can get expensive if such experiments are to be conducted at a large scale. Therefore, it is imperative to establish the scalability of the process and be able to conduct more experimentation at the lab and/or pilot scales. A section in this chapter discusses the challenges associated with scale-up of the high-shear wet granulation process, the various scale-up principles that are commonly used, and their broad classification into attribute-based and process parameter-based approaches. In addition, modeling tools that can be used to enhance our understanding of the process, and potentially allow for in silico design space development in the future are also discussed.