Application of Continuous Crystallization in an Integrated Continuous Pharmaceutical Pilot Plant

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• 作者：Haitao Zhang ; Richard Lakerveld ; Patrick L. Heider ; Mengying Tao ; Min Su ; Christopher J. Testa ; Alyssa N. D鈥橝ntonio ; Paul I. Barton ; Richard D. Braatz ; Bernhardt L. Trout ; Allan S. Myerson ; Klavs F. Jensen ; James M. B. Evans
• 刊名：Crystal Growth & Design
• 出版年：2014
• 出版时间：May 7, 2014
• 年：2014
• 卷：14
• 期：5
• 页码：2148-2157
• 全文大小：611K
• 年卷期：v.14,no.5(May 7, 2014)
• ISSN：1528-7505

文摘

Real-time control using process analytical technology (PAT) tools is required for the implementation of continuous crystallization within integrated continuous manufacturing (ICM) of pharmaceuticals. However, appropriate selection of PAT tools is challenging, and the design and operation of automated control loops for continuous crystallization within a continuous pharmaceutical process brings forward important questions. This paper discusses the process design and operation of a continuous reactive crystallization of aliskiren hemifumarate as part of an ICM pilot plant. Several PAT tools were used within automated control loops to satisfy specifications on the critical materials attributes of the crystallization process. The operational performance of the process was maintained for periods of time over 100 h. The purity of the targeted product exceeded 99%, and the process yield reached 91.4%.