Combined Cooling and Antisolvent Crystallization in Continuous Mixed Suspension, Mixed Product Removal Cascade Crystallizers: Steady-State and Startup Optimization

2015 ◽  
Vol 54 (21) ◽  
pp. 5673-5682 ◽  
Author(s):  
Yang Yang ◽  
Zoltan K. Nagy
Keyword(s):  
Steady State ◽  
Mixed Product ◽  
Product Removal ◽  
Mixed Suspension ◽  
Antisolvent Crystallization ◽  
Combined Cooling

scholarly journals The Role of Residence Time Distribution in the Continuous Steady-State Mixed Suspension Mixed Product Removal Crystallization of Glycine

2018 ◽  
Vol 19 (1) ◽  
pp. 66-80 ◽  
Author(s):  
Iyke I. Onyemelukwe ◽  
Anna R. Parsons ◽  
Helen P. Wheatcroft ◽  
Amy Robertson ◽  
Zoltan K. Nagy ◽  
...  
Keyword(s):  
Steady State ◽  
Residence Time ◽  
Time Distribution ◽  
Residence Time Distribution ◽  
Mixed Product ◽  
Product Removal ◽  
Mixed Suspension

scholarly journals Systematic Model-Based Steady State and Dynamic Optimization of Combined Cooling and Antisolvent Multistage Continuous Crystallization Processes

Proceedings ◽  
2020 ◽  
Vol 62 (1) ◽  
pp. 7
Author(s):  
Jiaxu Liu ◽  
Brahim Benyahia
Keyword(s):  
Steady State ◽  
Dynamic Optimization ◽  
Crystal Size ◽  
Balance Model ◽  
Mixed Product ◽  
Rigorous Approach ◽  
Product Removal ◽  
Startup Time ◽  
Total Residence Time ◽  
Combined Cooling

Currently, one of the key challenges in the pharmaceutical industry is the transformation of traditional batch production methods into robust continuous processes with the intention of reducing manufacturing costs and time and improving product quality. Crystallization is by far the most important purification technology in Pharma, as more than 80% of the active pharmaceutical ingredients (API) require at least one crystallization step. A successful crystallization process requires tight control over crystal size, shape and polymorphic purity. A rigorous and systematic methodology is presented to design and optimize multistage combined cooling and antisolvent continuous (mixed-suspension, mixed-product removal- MSMPR) crystallizers. The crystallization of acetylsalicylic acid (API) in ethanol (solvent) and water (anti-solvent) is used as a case study. A predictable and validated mathematical model of the system, which consists of a one-dimensional population balance model, was used to develop several optimizations strategies. Firstly, the attainable region of the mean particle size was determined for both minimum and maximum attainable crystal size. The method helped identify the most suitable number of stages and total residence time or volume for a cascade of continuous crystallizers. This was followed by a steady state optimization which helped determine the optimal operating temperatures and antisolvent flowrates. To minimize the startup time, a series of dynamic optimization strategies were implemented, assuming starting from empty vessels. The optimal dynamic profiles of the temperature and antisolvent flow rate, at different crystallization steps, were identified using a systematic and rigorous approach allowing a reduction in the startup time by 31%.

A small-scale continuous mixed suspension mixed product removal crystallizer

1991 ◽  
Vol 46 (2) ◽  
pp. 709-711 ◽  
Author(s):  
Nishio S. ◽  
Kavanagh J.P. ◽  
J. Garside
Keyword(s):  
Small Scale ◽  
Mixed Product ◽  
Product Removal ◽  
Mixed Suspension

Development of Continuous Crystallization Processes Using a Single-Stage Mixed-Suspension, Mixed-Product Removal Crystallizer with Recycle

2012 ◽  
Vol 12 (11) ◽  
pp. 5701-5707 ◽  
Author(s):  
Shin Yee Wong ◽  
Adam P. Tatusko ◽  
Bernhardt L. Trout ◽  
Allan S. Myerson
Keyword(s):  
Single Stage ◽  
Mixed Product ◽  
Continuous Crystallization ◽  
Product Removal ◽  
Mixed Suspension
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