Particle Size Control in Batch Crystallization of Pyrazinamide on Different Scales

A methodology to achieve consistent particle size in seeded batch crystallization on two scales (0.5 and 10 L) was demonstrated using pyrazinamide as a model compound. An empirical process model was established from a Design of Experiment study on the 500 mL scale and subsequently verified by correlating D50 of the crystals with stirrer speed, seed size, and seed loading. Experiments on the 10 L scale showed that the criterion of equivalent impeller tip speed produced a larger D50 than that of equivalent input energy. The process model derived from the 0.5 L scale was demonstrated to work well for process parameter adjustment to obtain the target product size on the 10 L scale. Some practical issues in crystallization development are discussed.

[1]  Alan Jones,et al.  Scale-up of Continuous and Semibatch Precipitation Processes , 2000 .

[2]  Wolfgang Beckmann,et al.  Seeding the Desired Polymorph: Background, Possibilities, Limitations, and Case Studies , 2000 .

[3]  Thanassi E. Fakatselis.  Residence Time Optimization in Continuous Crystallizers , 2002 .

[4]  Noriaki Kubota,et al.  Seeding Effect on Product Crystal Size in Batch Crystallization , 2002 .

[5]  E. L. Paul,et al.  Handbook of Industrial Mixing , 2003 .

[6]  J. Derksen.  Long-time Solids Suspension Simulations by Means of a Large-Eddy Approach , 2006 .

[7]  Eva Roblegg,et al.  Continuous Sonocrystallization of Acetylsalicylic Acid (ASA): Control of Crystal Size , 2012 .

[8]  S. Y. Wong,et al.  Development of Continuous Crystallization Processes Using a Single-Stage Mixed-Suspension, Mixed-Product Removal Crystallizer with Recycle , 2012 .

[10]  Jyeshtharaj B. Joshi,et al.  Effect of impeller design and power consumption on crystal size distribution , 2014 .

[11]  R. Tan,et al.  Design Space for Polymorphic Co-crystallization: Incorporating Process Model Uncertainty and Operational Variability , 2014 .

[12]  R. Braatz,et al.  Continuous-Flow Tubular Crystallization in Slugs Spontaneously Induced by Hydrodynamics , 2014 .

[13]  R. Tan,et al.  Robust Crystallization Process Development for the Metastable δ-form of Pyrazinamide , 2015 .

[14]  G. Janiga,et al.  Coupled Computational Fluid Dynamics–Discrete Element Method Simulations of a Pilot-Scale Batch Crystallizer , 2015 .

[15]  Patrick J. Frawley,et al.  Application of the Lagrangian meshfree approach to modelling of batch crystallisation: Part I—Modelling of stirred tank hydrodynamics , 2016 .