High accuracy online measurement of multidimensional particle size distributions during crystallization

A novel stereoscopic image acquisition setup and a procedure for measuring multidimensional particle size distributions (nD PSDs) during crystallization based on image analysis are presented. Images of crystals in suspension passing a flow through cell are generated by two cameras which are arranged in an orthogonal manner. Particles are conveyed to the flow through cell using a sampling loop, thus allowing for online monitoring. Automated image analysis provides contour data which can be used to classify crystals into different generic particle model classes. For each type of particle size data is calculated and stored. Finally, time resolved nD PSD data can be calculated. The accuracy of this novel size measurement was confirmed by comparison to measurements obtained with a Coulter Multisizer. The non-invasive nature and repeatability of experiments are shown by monitoring populations of sodium chloride and of the β polymorph of l-glutamic acid under different conditions. Finally, crystal growth of acetaminophen during cooling crystallization is shown. In addition, a virtual test bench is used to study the measurement method in silico. © 2013 Elsevier Ltd.