Progress of Pharmaceutical Continuous Crystallization

Dejiang Zhang, Shijie Xu, Shichao Du, Jingkang Wang, Junbo Gong

Engineering ›› 2017, Vol. 3 ›› Issue (3) : 354-364.

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Engineering ›› 2017, Vol. 3 ›› Issue (3) : 354-364. DOI: 10.1016/J.ENG.2017.03.023
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Progress of Pharmaceutical Continuous Crystallization

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Abstract

Crystallization is an important unit operation in the pharmaceutical industry. At present, most pharmaceutical crystallization processes are performed in batches. However, due to product variability from batch to batch and to the low productivity of batch crystallization, continuous crystallization is gaining increasing attention. In the past few years, progress has been made to allow the products of continuous crystallization to meet different requirements. This review summarizes the progress in pharmaceutical continuous crystallization from a product engineering perspective. The advantages and disadvantages of different types of continuous crystallization are compared, with the main difference between the two main types of crystallizers being their difference in residence time distribution. Approaches that use continuous crystallization to meet different quality requirements are summarized. Continuous crystallization has advantages in terms of size and morphology control. However, it also has the problem of a process yield that may be lower than that of a batch process, especially in the production of chirality crystals. Finally, different control strategies are compared.

Keywords

Continuous crystallization / Pharmaceutical / MSMPR / Tubular crystallizer / Control strategy

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Dejiang Zhang, Shijie Xu, Shichao Du, Jingkang Wang, Junbo Gong. Progress of Pharmaceutical Continuous Crystallization. Engineering, 2017, 3(3): 354‒364 https://doi.org/10.1016/J.ENG.2017.03.023

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Acknowledgements

The authors are grateful to the financial support of the National Natural Science Foundation of China (81361140344, 21676179, and 21376164), the “863” Program (2015AA021002), the Major Project of Tianjin (15JCZDJC33200), the National Major Scientific Instrument Development Project (21527812), and the National Major Science and Technology Program for Water Pollution Control and Treatment (2015ZX07202-13).

Compliance with ethics guidelines

Dejiang Zhang, Shijie Xu, Shichao Du, Jingkang Wang, and Junbo Gong declare that they have no conflict of interest or financial conflicts to disclose.
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2017 2017 THE AUTHORS. Published by Elsevier LTD on behalf of the Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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