Characterization and modelling of antisolvent crystallization of salicylic acid in a continuous oscillatory baffled crystallizer

Abstract Using antisolvent crystallisation of salicylic acid as the model process, we report our experimental investigation into the temporal and spatial steady states of solution concentration and mean crystal size in a continuous oscillatory baffled crystallizer. The evolutions of the two parameters over time and distance along the crystallizer are measured for a variety of operating conditions. The results show that the attainment of long term temporal and spatial stabilities (>100 residence times) for the solute concentrations are easily achieved, whereas the temporal steady states of the mean crystal size are more difficult to accomplish, even though the spatial steady states have been obtained. A simplified population balance model is applied to the experimental data for the determination of nucleation and growth kinetic parameters. From which both the solution concentration and the mean size were predicted and matched to experimental values reasonably well. In addition, we have identified and executed the conditions of long term steady states for extended operation of 6.25 h to produce close to 1 kg of crystal product with minimal variation in crystal size (±3.01 μm).

[1]  A. Mahajan,et al.  Rapid precipitation of biochemicals , 1993 .

[2]  Xiongwei Ni,et al.  Effects of mixing, seeding, material of baffles and final temperature on solution crystallization of l-glutamic acid in an oscillatory baffled crystallizer , 2010 .

[3]  Denis Mangin,et al.  Kinetics identification of salicylic acid precipitation through experiments in a batch stirred vessel and a T-mixer , 2001 .

[4]  Michael Manhart,et al.  Precipitation of nanoparticles in a T-mixer: Coupling the particle population dynamics with hydrodynamics through direct numerical simulation , 2006 .

[5]  A. Randolph,et al.  Theory of Particulate Processes: Analysis and Techniques of Continuous Crystallization , 1971 .

[6]  Richard D. Braatz,et al.  Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review , 2015 .

[7]  Allan S. Myerson,et al.  Continuous Plug Flow Crystallization of Pharmaceutical Compounds , 2010 .

[8]  R. I. Ristic,et al.  Oscillatory Mixing for Crystallization of High Crystal Perfection Pharmaceuticals , 2007 .

[9]  Gerry Steele,et al.  Continuous Crystallization of Pharmaceuticals Using a Continuous Oscillatory Baffled Crystallizer , 2009 .

[10]  Kevin J. Roberts,et al.  On the Crystal Polymorphic Forms of l-Glutamic Acid Following Temperature Programmed Crystallization in a Batch Oscillatory Baffled Crystallizer , 2004 .

[11]  Å. Rasmuson,et al.  Solubility and Melting Properties of Salicylic Acid , 2006 .

[12]  Åke C. Rasmuson,et al.  Reaction crystallization kinetics of benzoic acid , 2001 .

[13]  James J. De Yoreo,et al.  Crystallization of Paracetamol under Oscillatory Flow Mixing Conditions , 2004 .

[14]  Zoltan K. Nagy,et al.  Population Balance Model-Based Multiobjective Optimization of a Multisegment Multiaddition (MSMA) Continuous Plug-Flow Antisolvent Crystallizer , 2014 .

[15]  E. L. Paul,et al.  Investigation of impinging‐jet crystallization with a calcium oxalate model system , 2003 .

[16]  Ying Liu,et al.  CFD predictions for chemical processing in a confined impinging‐jets reactor , 2006 .

[17]  Narayan S. Tavare,et al.  Mixing in continuous crystallizers , 1986 .

[18]  Zoltan K. Nagy,et al.  Recent advances in the monitoring, modelling and control of crystallization systems , 2013 .

[19]  M. Fakhree,et al.  Solubility of 2-Hydroxybenzoic Acid in Water, 1-Propanol, 2-Propanol, and 2-Propanone at (298.2 to 338.2) K and Their Aqueous Binary Mixtures at 298.2 K , 2012 .

[20]  Hongbing Jian,et al.  A Numerical Study on the Scale-Up Behaviour in Oscillatory Baffled Columns , 2005 .

[21]  Narayan Variankaval,et al.  From Form to Function: Crystallization of Active Pharmaceutical Ingredients , 2008 .

[22]  A. Randolph,et al.  A Model for the Precipitation of Pentaerythritol Tetranitrate (PETN) , 1978 .

[23]  M. Baird,et al.  Scale-up of single phase axial dispersion coefficients in batch and continuous oscillatory baffled tubes , 2001 .

[24]  P. Stonestreet,et al.  The Effects of Oscillatory Flow and Bulk Flow Components on Residence Time Distribution in Baffled Tube Reactors , 1999 .