Recent Developments in the Crystallization Process： Toward the Pharmaceutical Industry

• Published in: Engineering (Beijing, China) Vol. 3; no. 3; pp. 343 - 353
• Main Authors: Gao, Zhenguo, Rohani, Sohrab, Gong, Junbo, Wang, Jingkang
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-06-2017; Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada; School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China%Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada%School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Elsevier
• Subjects: Crystal engineering; Crystal size distribution; Crystallization; Crystallization process design and control; Polymorphism; Crystal engineering; Crystallization process design and control; Crystallization; Polymorphism; Crystal size distribution
• ISSN: 2095-8099
• DOI: 10.1016/j.eng.2017.03.022

Crystallization is one of the oldest separation and purification unit operations, and has recently contributed to significant improvements in producing higher-value products with specific properties and in building efficient manufacturing processes. In this paper, we review recent developments in crystal engineering and crystallization process design and control in the pharmaceutical industry. We systematically summarize recent methods for understanding and developing new types of crystals such as co-crystals, polymorphs, and solvates, and include several milestones such as the launch of the first co-crystal drug, Entresto （No- vartis）, and the continuous manufacture of Orkambi （Vertex）. Conventional batch and continuous processes, which are becoming increasingly mature, are being coupled with various control strategies and the recently developed crystallizers are thus adapting to the needs of the pharmaceutical industry. The development of crystallization process design and control has led to the appearance of several new and innovative crystal- lizer geometries for continuous operation and improved performance. This paper also reviews major recent orogress in the area of process analytical technology.