CRYSTALLIZATION DESIGN AND SCALE‐UP

Crystallization can be defined as the formation of a solid crystalline phase of a chemical compound from a solution in which the compound is dissolved. This chapter provides a concise, basic understanding of crystallization design and scale-up principles, which the reader can apply toward common industrial problems. The focus is on batch rather than continuous crystallization processes, as batch crystallization is the predominant processing method used in the pharmaceutical industry today. The chapter discusses crystallization design objectives and constraints on design, including a description of physical properties important to product performance. It then reviews thermodynamic principles of crystallization and also discusses crystallization kinetics. The chapter also presents common modes of crystallization design which integrate thermodynamic and kinetic principles, along with scale-up considerations for each mode. Finally, it also reviews advanced topics relevant to crystallization of pharmaceutical compounds. Throughout the chapter, industrially relevant examples are used to illustrate the concepts presented.