Modification of Crystal Shape through Deep Temperature Cycling

Abstract

The evolution of particle shape is an important consideration in many industrial crystallizations. This article describes the design of temperature-cycling experiments (between alternating positive and negative supersaturations) to substantially change crystal shape with only a small number of cycles. The growth and dissolution of monosodium glutamate crystals of varying shapes were monitored using in-process attenuated total reflection−Fourier transform infrared spectroscopy (ATR-FTIR), focused beam reflectance measurement (FBRM), particle vision and measurement (PVM), and off-line optical microscopy. The growth and dissolution kinetics were estimated in a multidimensional population balance model based on solute concentration and crystal dimension measurements. This model fitted the experimental data with a limited number of parameters of small uncertainty. In addition, with the estimated kinetic parameters, the model predicted the crystal size and shape distribution in a different temperature-cycling experiment reasonably well. In contrast to previous studies that have estimated kinetics along multiple crystal axes in mixed-tank crystallizers, this study implements dissolution terms in the multidimensional population balance model along multiple axes.

Optimized Stirred Reactor for Enhanced Particle Dispersion

“…One tank had a cylindrical focused beam reflectance measurement (FBRM) probe (G400, outer diameter of probe tip 9.5 mm) and ReactIR probe (DST Series, outer diameter of probe tip 9.5 mm) inside the slurry, while the other had a particle vision measurement (PVM) probe (Lasentec V819L, outer diameter of probe tip 19 mm). FBRM, PVM, and infrared (IR) probes are common process analytical technologies used for pharmaceutical and other industries 28, although these probes were used only as geometrical obstacles for flow in this paper.…”

“…In addition, the principle of the mixing design is applied to a standard cooling crystallization process in non‐baffled mixed tanks. In the pharmaceutical industry, mixing is an important factor which is often difficult to be manipulated or scaled up in batch crystallizers to satisfy a target size distribution 27–29. One way to enhance the control of product size distribution is to reduce secondary nucleation, which sometimes derives from poor mixing.…”

Mathematical modelling and experimental validation of a novel periodic flow crystallization using MSMPR crystallizers

“…In the future work, a multiple dimensional population balance model would be necessary to reduce the prediction error and control the crystal shape. 32,33,34 Correspondingly, in-situ PVM images providing the crystal shape and size measurements are also highly demanded. 35 To sum up accordingly, the estimated crystallization mechanism and kinetics from batch cooling crystallization experiments have been shown with good predictive capability either in coupled periodic flow crystallization in single-/ three-stage MSMPR crystallizers or in decoupled periodic flow crystallization in a single-stage crystallizer, which proves its further implementation in process design, optimisation, and control.…”

Control of self-assembly in micro- and nano-scale systems

“…Another related example is the use of temperature cycling in crystallization to change crystal shape, enhance crystal size uniformity, and increase polymorphic purity [50,51].…”