Crystal Aggregation in a Flow Tube: Image-Based Observation

The aggregation of crystals within a flow tube was observed based on data extracted from images of the bypassing population. The experiments were conducted under different conditions, namely the flow rate and the particle concentration have been varied simultaneously and two different solvents were used in which the aggregation extent was found to be different under otherwise constant conditions. The analysis of images of bypassing crystals allows for the acquisition of rich datasets both in terms of the variety of shape descriptors and number of particles. This amount of data enables the determination of at least bivariate number distributions of high accuracy with simple histograms. The interpretation of the data is further improved with kernel histograms with which also higher-dimensional volume distributions can be obtained in good quality based on relatively few data points. Indeed, the isosurfaces of 3D distributions turned out to be helpful for inspection of the acquired data.

[1]  R. Rosmalen,et al.  The Influence of the Hydrodynamic Environment on the Growth and the Formation of Liquid Inclusions in Large Potassium Dihydrogen Phosphate (KDP) Crystals , 1978 .

[2]  B. Silverman Density estimation for statistics and data analysis , 1986 .

[3]  Matheo Lue Raphael,et al.  Recovery and kinetics study of isoelectric precipitation of sunflower protein in a tubular precipitator , 1995 .

[4]  K. Sangwal Growth kinetics and surface morphology of crystals grown from solutions: Recent observations and their interpretations , 1998 .

[5]  B. Shekunov,et al.  CRYSTALLIZATION PROCESSES IN PHARMACEUTICAL TECHNOLOGY AND DRUG DELIVERY DESIGN , 2000 .

[6]  Richard D. Braatz,et al.  Advanced control of crystallization processes , 2002, Annu. Rev. Control..

[7]  Jörg Raisch,et al.  Population balance modelling and H∞-controller design for a crystallization process , 2002 .

[8]  Jörg Raisch,et al.  Modeling, simulation and stabilizing H∞-control of an oscillating continuous crystallizer with fines dissolution , 2003 .

[9]  Å. Rasmuson,et al.  Characterization of paracetamol agglomerates by image analysis and strength measurement , 2003 .

[10]  Paul H. C. Eilers,et al.  Enhancing scatterplots with smoothed densities , 2004, Bioinform..

[11]  Richard D. Braatz,et al.  First-principles and direct design approaches for the control of pharmaceutical crystallization , 2005 .

[12]  Kevin J. Roberts,et al.  Classifying organic crystals via in-process image analysis and the use of monitoring charts to follow polymorphic and morphological changes , 2005 .

[13]  A. Seidel-Morgenstern,et al.  Crystal Growth Kinetics via Isothermal Seeded Batch Crystallization: Evaluation of Measurement Techniques and Application to Mandelic Acid in Water , 2005 .

[14]  Jörg Raisch,et al.  Control of batch crystallization—A system inversion approach , 2006 .

[15]  Kevin J. Roberts,et al.  Integration of crystal morphology modeling and on‐line shape measurement , 2006 .

[16]  Andreas Seidel-Morgenstern,et al.  Parameterization of population balance models for polythermal auto seeded preferential crystallization of enantiomers , 2009 .

[17]  Å. Rasmuson,et al.  Agglomeration and adhesion free energy of paracetamol crystals in organic solvents , 2007 .

[18]  Marco Mazzotti,et al.  Measurement of particle size and shape by FBRM and in situ microscopy , 2008 .

[19]  Zoltan K. Nagy,et al.  Model based robust control approach for batch crystallization product design , 2009, Comput. Chem. Eng..

[20]  K. Sundmacher,et al.  On the Prediction of Crystal Shape Distributions in a Steady State Continuous Crystallizer , 2009 .

[21]  H. Briesen Two-dimensional population balance modeling for shape dependent crystal attrition , 2009 .

[22]  Ingmar Nopens,et al.  Celebrating a milestone in Population Balance Modeling , 2009 .

[23]  K. Sundmacher,et al.  Model Based Prediction of Crystal Shape Distributions , 2009 .

[24]  Marco Mazzotti,et al.  Measurement of 3D particle size distributions by stereoscopic imaging , 2010 .

[25]  Modeling of crystal morphology distributions. Towards crystals with preferred asymmetry , 2010 .

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

[27]  C. Ma,et al.  Modelling protein crystallisation using morphological population balance models , 2010 .

[28]  Stefan Radl,et al.  Continuously Seeded, Continuously Operated Tubular Crystallizer for the Production of Active Pharmaceutical Ingredients , 2010 .

[29]  Jiří Zelinka,et al.  Kernel Density Estimation Toolbox for Matlab , 2011 .