Measuring multidimensional particle size distributions during crystallization

Abstract A protocol for measuring multidimensional particle size distributions during crystallization is presented. The instrument consists of a flow through cell where it is possible to take images of particles in suspension from two perpendicular directions. The flow through cell is connected to a batch crystallizer through a sampling loop and a dilution system that allow tuning the suspension density in the cell for the sake of image quality. The images thus obtained are analyzed with a fast image analysis algorithm and characteristic lengths of particles are calculated. Generic geometric shapes representing different types of crystals are defined as particle classes. We present a method to classify particles into these classes, which enables for instance to differentiate between different polymorphs of a substance when their shape is different. The capabilities of the measurement device and of the algorithm are illustrated by comparing their performance to standard measurement tools like a Coulter Multisizer. The comparison shows that the two instruments give the same result. The effectiveness and accuracy of the protocol proposed is assessed by monitoring size and shape of crystals of acetylsalicylic acid and of paracetamol during seeded cooling crystallization.

[1]  Kevin J. Roberts,et al.  Real-Time Measurement of the Growth Rates of Individual Crystal Facets Using Imaging and Image Analysis: A Feasibility Study on Needle-shaped Crystals of L-Glutamic Acid , 2007 .

[2]  Michael F. Doherty,et al.  Shape evolution of 3‐dimensional faceted crystals , 2006 .

[3]  James B. Rawlings,et al.  Particle-shape monitoring and control in crystallization processes , 2001 .

[4]  Kevin J. Roberts,et al.  Multi-scale segmentation image analysis for the in-process monitoring of particle shape with batch crystallisers , 2005 .

[5]  Marco Mazzotti,et al.  Measurement of size and shape distributions of particles through image analysis , 2008 .

[6]  Ka Ming Ng,et al.  New discretization procedure for the breakage equation , 1995 .

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

[8]  James B. Rawlings,et al.  Model-based object recognition to measure crystal size and shape distributions from in situ video images , 2007 .

[9]  L. L. Simon,et al.  Endoscopy-Based in Situ Bulk Video Imaging of Batch Crystallization Processes , 2009 .

[10]  James B. Rawlings,et al.  An algorithm for analyzing noisy, in situ images of high-aspect-ratio crystals to monitor particle size distribution , 2006 .

[11]  Marco Mazzotti,et al.  Monitoring the particle size and shape in the crystallization of paracetamol from water , 2010 .

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

[13]  D. Ramkrishna,et al.  On the solution of population balance equations by discretization - III. Nucleation, growth and aggregation of particles , 1997 .

[14]  Thomas J. Naughton,et al.  Microparticle characterization using digital holography , 2010 .

[15]  M. Mazzotti,et al.  Precipitation of L‐Glutamic Acid: Determination of Nucleation Kinetics , 2006 .

[16]  Margaritis Kostoglou,et al.  On the steady-state size distribution of dispersions in breakage processes , 1997 .

[17]  Rafael C. González,et al.  Digital image processing using MATLAB , 2006 .

[18]  Zoltan K. Nagy,et al.  Bulk video imaging based multivariate image analysis, process control chart and acoustic signal assisted nucleation detection , 2010 .

[19]  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 .

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

[21]  Marco Mazzotti,et al.  Monitoring size and shape during cooling crystallization of ascorbic acid , 2009 .

[22]  J. Hostomský,et al.  Calcium carbonate crystallization, agglomeration and form during continuous precipitation from solution , 1991 .

[23]  L. L. Simon,et al.  Comparison of external bulk video imaging with focused beam reflectance measurement and ultra-violet visible spectroscopy for metastable zone identification in food and pharmaceutical crystallization processes , 2009 .

[24]  M. Mazzotti,et al.  L-Glutamic Acid Precipitation : Agglomeration Effects , 2008 .

[25]  M. Mazzotti,et al.  Precipitation of αL-glutamic acid: determination of growth kinetics , 2007 .

[26]  Kevin J. Roberts,et al.  Crystal growth measurement using 2D and 3D imaging and the perspectives for shape control , 2008 .