Designing Continuous Crystallization Platforms - METTLER TOLEDO

Designing Continuous Crystallization Platforms

PAT Based Continuous Crystallizations

This webinar describes an investigation into the characterization, design and operation of continuous crystallization. Robust crystallization processes are designed across multiple batch and continuous configurations.
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 minutes
English
Designing Continuous Crystallization Platforms

A continuous crystallization platform was developed that allowed Process Analytical Technologies (PAT) to be applied in situ via the use of novel flow cells. This crystallization platform was used to develop the anti-solvent crystallization of benzoic acid from aqueous ethanol solution. 2, 3 The equivalent tank based Mixed-Suspension, Mixed-Product-Removal (MSMPR) crystallization was also characterized using PAT in a continuous stirred tank utilizing a pneumatic slurry transfer technique.1,4,5  These continuous crystallizations were compared to the equivalent batch crystallizations so that a true measure of performance of the continuous crystallizations could be made.1 As expected the continuous crystallizations offered hugely intensified production with approximately the same amount of material generated by a ~40 ml plug flow, 9 L MSMPR and 42, 10,000 L batch crystallizations per annum. Furthermore, the alternate process dynamics and mixing environments offered by the plug flow and MSMPR enabled a wider range of particle sizes and morphologies to be produced than would be available if only the batch crystallization options were considered.1,3

Use of in situ PAT permits significant reductions in process development time and can also be applied to monitoring and control of continuous industrial crystallizations. It is hoped that such methods can facilitate the inclusion of continuous crystallizer configurations in standard pharmaceutical commercialization procedures.

Guest Presenter – Steven Ferguson

Steven currently works in the Chemical Process R&D group at Biogen Idec in Cambridge, MA where he focuses on the development, scale-up and optimization of small molecule API processes from pre-clinical targets to commercial processes with a focus on crystallization. Prior to this, Steven spent a couple of years at the Novartis-MIT Centre for Continuous Manufacturing as a Postdoctoral Associate in the Myerson/Trout Research Groups at MIT. While there, he completed multiple projects with a focus on continuous crystallization and isolation, polymorphism and membrane purification.

Steven's PhD research was on the development of continuous crystallization technology for pharmaceutical applications. This was in the Glennon Research Group (SSPC) at the University College Dublin (UCD) and focused on the design of high intensity tubular crystallizers and continuous stirred tank crystallizers as well as the development of rapid characterization and optimization techniques via novel PAT applications.

Contributor: Brian Glennon, Solid State Pharmaceutical Cluster, School of Chemical and Bioprocess Engineering, University College Dublin.

Presentation references

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.

Publications

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

7. Tsai-Ta C. Lai, Steven Ferguson, Laura Palmer, Bernhardt L. Trout, and Allan S. Myerson, 2014. Continuous Crystallization and Polymorph Dynamics in the l-Glutamic Acid System. Org. Process Res. Dev, Article ASAP