基于 PAT 的连续结晶设计 - 梅特勒-托利多
点播网络研讨会

基于 PAT 的连续结晶设计

点播网络研讨会

活塞流动和 MSMPR 结晶

讨论了通过过程分析技术 (PAT) 实现的设计方法,可实现各种连续活塞流动和 MSMPR 结晶(及其相应批次)的快速评估。
Steven Ferguson, 1. Solid State Pharmaceutical Cluster, School of Chemical and Bioprocess Engineering, University College Dublin. 2. Novartis-MIT Center for Continuous Manufacturing & Department of Chemical Engineering Massachusetts Institute of Technology. Now at Biogen, Idec, Cambridge, MA
25 分钟
English

活塞流动结晶平台被开发出来,可通过使用新型流通池原位应用过程分析技术(FBRM、PVM、FTIR)。 使用此结晶平台,利用乙醇水溶液开发苯甲酸的抗溶剂结晶。2, 3基于等效罐的 MSMPR 结晶在利用气动浆料转移技术的连续搅拌罐中用 PAT 表征。1,4,5  这些连续结晶与等效批次结晶比较,这样就可以实现连续结晶性能的真实测量。1正如预期的那样,连续结晶提供了非常强劲的生产能力,每年 ~40 ml 活塞流量、9 L MSMPR 和 42, 10,000 L 批次结晶所产生的材料量大致相同。 此外,活塞流量和 MSMPR 提供的替代过程动态和搅拌环境生产的颗粒尺寸和形态范围比仅仅考虑批次结晶选项时要广泛。1,3

利用原位 PAT 可大大减少过程开发时间,还可用于监控连续工业结晶。 希望这些方法可以便于将连续结晶器配置纳入标准制药商业化程序中。

特邀发言人 — Steven Ferguson

Steven 目前就职于马萨诸塞州剑桥城 Biogen Idec 的 Chemical Process R&D 集团,专注于开发、扩大并优化从前期临床目标到商业过程的小分子 API 工艺,工作重点是结晶。 在此之前,Steven 在 MIT 的 Myerson/Trout Research Groups 担任博士后副研究员,在 Novartis-MIT 连续制造中心任职了几年。 在那里,他完成了多个项目,工作重点是连续结晶和分离、多晶态和膜纯化。

Steven 的博士研究课题是面向制药应用开发连续结晶技术。 这是在都柏林大学 (UCD) 的 Glennon Research Group (SSPC) 完成的,重点是高强度管结晶器和连续搅拌罐结晶器的设计,以及通过新型 PAT 应用开发快速表征和优化技术。

贡献者: 都柏林大学化学和生物过程工程学院固态医药专业,Brian Glennon

参考文献

1.     Ferguson, S., Morris, G., Hao, H., Barrett, M., Glennon, B., 2013.Characterization of anti-solvent batch, plug flow and MSMPR crystallization of benzoic acid. Chem. Eng. Sci. 104, 44-54.

2.     Ferguson, S., Morris, G., Hao, H., Barrett, M., Glennon, B., 2012. In-situ Monitoring and Characterization of Plug Flow Crystallizers. Chem. Eng. Sci. 77, 105-111.

3.     Ferguson, S., Morris, G., Hao, H., Barrett, M., Glennon, B., 2014. Automated self-seeding of batch crystallizations via plug flow seed generation. Chem. Eng. Res & Des. http://www.sciencedirect.com/science/article/pii/S0263876214000689

4.     Morris, G.; Hou, G.; Barrett, M.; Ferguson, S.; Glennon, B. Development and  Characterization of a Multistage Continuous Cooling Crystallization Process using In-line Process Analytical Technology (PAT). Cryst. Growth Des. 2014, Submitted

5.     Hou, G., Power, G., Barrett, M., Glennon, B., Morris, G., Zhao, Y. 2014. Development and Characterization of a Single Stage Mixed- Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit. Cryst. Growth & Des. 14 (2), 617- 627.3.

出版物

1.     Hao, H., Barrett, M., Hu, Y., Su., W., Ferguson, S., Wood, B., Glennon, B., 2012.The use of In-situ tools to monitor the enantiotropic transformation of p-aminobenzoic acid polymorphs. Org. Process. Res. Dev, 16 (1),  35-41.

2.     Ferguson, S., Morris, G., Hao, H., Barrett, M., Glennon, B., 2012. In-situ Monitoring and Characterization of Plug Flow Crystallizers. Chem. Eng. Sci. 77, 105-111.

3.     Ferguson, S., Morris, G., Hao, H., Barrett, M., Glennon, B., 2013.Characterization of anti-solvent batch, plug flow and MSMPR crystallization of benzoic acid. Chem. Eng. Sci. 104, 44-54.

4.     Ferguson, S., Ortner, O., Quon, J., Peeva, L., Livingston, Trout, B.L., Myerson, A.S. 2014. Use of continuous MSMPR crystallization with integrated nanofiltration membrane recycle for enhanced yield and purity in API crystallization. Chem. Eng. Sci. 14 (2), 617- 627.

5.     Ferguson, S., Morris, G., Hao, H., Barrett, M., Glennon, B., 2014. Automated self-seeding of batch crystallizations via plug flow seed generation. Chem. Eng. Res & Des. http://www.sciencedirect.com/science/article/pii/S0263876214000689

6.     Characterization of a Multistage Continuous Cooling Crystallization Process using In-line Process Analytical Technology (PAT). Cryst. Growth Des. 2014, Submitted

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