Crystallization is an essential unit operation in the pharmaceutical manufacturing because the majority of active pharmaceutical ingredients (APIs) are produced in solid form. Yet, this subject remains much less a part of the academic curriculum up today, compared to other topics such as distillation, extraction, and reaction. Engineers or chemists will need to learn crystallization process development on the job through actual practice.

Based on the authors' hands-on experiences as process engineers this book guides readers through the practical applications of crystallization. Through the use of case studies and examples of crystallization processes, ranging from laboratory development through manufacturing scale-up, the book emphasizes strategies that have proven to be successful and helps readers avoid common pitfalls that can render standard procedures unsuccessful. Most chapters feature multiple examples that guide readers step by step through the crystallization of active pharmaceutical ingredients (APIs). An analysis of the major methods of carrying out crystallization operations, their strengths and potential issues, as well as numerous examples of crystallization processes from development through manufacturing scale is also included.

Advancements in the field of crystallization have been integrated throughout the book in the new edition to ensure the content adequately reflects current industrial know-hows and practice. The new edition also adds chapters addressing downstream operations after the crystallization which yield dry API, including filtration/washing and drying/delumping, together with industrial cases.

Hsien-Hsin Tung, PhD, is the co-founder of AcrysPharm, LLC. He founded the crystallization lab. at Merck and center of excellence of particle engineering at Abbive.

Edward L. Paul, PhD, (deceased) was retired Director of Chemical Engineering R & D at Merck Research Laboratories.

Michael Midler, PhD, (deceased) was retired Senior Investigator, Chemical Engineering R&D at Merck.

James A. McCauley, PhD, was a senior investigator in the Analytical R & D at Merck until his retirement, after which he became an adjunct professor in the Department of Chemical and Biochemical Engineering at Rutgers University.

Preface

Chapter 1            Introduction to Crystallization

Chapter 2            Properties

Chapter 3            Polymorphism

Chapter 4            Kinetics

Chapter 5            Mixing and Crystallization

Chapter 6            Critical Issues and Quality by Design

Chapter 7            Cooling Crystallization

Chapter 8            Evaporative Crystallization

Chapter 9            Antisolvent Crystallization

Chapter 10          Reactive Crystallization

Chapter 11          Filtration

Chapter 12          Drying

Chapter 13          Special Applications