Measurement, modelling, and closed-loop control of crystal shape distribution: Literature review and future perspectives

Abstract

Crystal morphology is known to be of great importance to the end-use properties of the crystal product and affect the down-stream processing such as in filtration and drying, but was previously regarded as too challenging to achieve automatic closed-loop control. As a consequence, previous work has focused on control the crystal size distribution (CSD) where the size of a crystal is often defined as the diameter of a sphere that has the same volume of the crystal. This paper reviews very promising new advances made in recent years in morphological population balance models for modelling and simulation of crystal shape distribution (CShD), measurement and estimation of crystal facet growth kinetics, as well as in 2D and 3D imaging for on-line characterisation of crystal morphology and CShD. A framework is presented integrating various components in order to achieve the ultimate objective of model-based closed-loop control of CShD. The knowledge gaps and challenges that require further research are also identified.

Investigation of the operating conditions to morphology evolution of β-l-glutamic acid during seeded cooling crystallization

“…Little result, however, had been cultivated for the CShD related to crystal aspect ratio during crystallization, due to the limitation of measurement and available PATs. With the development of on-line imaging systems for real-time monitoring of crystallization processes, it has become possible to measure the shapes of particles during a crystallization process, and therefore increasing efforts have been devoted to the crystal shape control in the recent years [1,2]. Figure 6 shows the CShDs under different operating conditions, based on using the in-situ imaging analysis method [13].…”

“…Due to the fact that it was not easy to measure the crystal shapes during a crystallization process, evaluation of crystal morphology evolution during crystallization had been mainly simplified as estimating the one-dimensional crystal size distribution (CSD) in the literature [1]. With the development of real-time process analytical technology (PAT) in the recent years, on-line measurement of crystal morphology has become available and attracted increasing attentions to study the dynamic evolution of crystal population during crystallization [1,2].…”

Improved Understanding of Cefixime Trihydrate Reactive Crystallization and Process Scale-up with the Aid of PAT

“…PAT instrument studied for crystallization includes ATR-FTIR, online imaging, ultrasound, and Raman; and the work has been reviewed in some review and research articles. [16][17][18][19][20][21][22][23] In this work, on-line imaging and ATR-FTIR were used to find and define the operational envelopes leading to desired CSDs. The PAT instrument was applied during experiments to qualitatively and quantitatively characterize the crystal growth of azithromycin and polymorph transition and study the effects of several variables including the addition of water as an anti-solvent, temperature, and stirrer speed.…”

Simulations of crystal aggregation and growth: Towards correct crystal area

“…Apart from performing experiments, the evolution of these properties can also be examined by modeling the crystallization process using the population balance approach . This method, as well as the involved crystallization phenomena and challenges related to shape control have been reviewed in the literature . One of the main challenges lies in the complexity of the crystal shape and the changes it undergoes during crystallization .…”