Title: Pharmaceutical crystal shape control based on online image processing and multi-scale modelling

Authors: Xue Z. Wang, Cai Y. Ma, Jian Wan

Addresses: Institute of Particle Science and Engineering, School of Process, Environmental and Materials Engineering, University of Leeds, Leeds LS2 9JT, UK. ' Institute of Particle Science and Engineering, School of Process, Environmental and Materials Engineering, University of Leeds, Leeds LS2 9JT, UK. ' Institute of Particle Science and Engineering, School of Process, Environmental and Materials Engineering, University of Leeds, Leeds LS2 9JT, UK

Abstract: Pharmaceutical crystals grown from solution are known to exhibit multiple morphological forms and habits which are of great importance to the end use properties of the product such as the bioavailability and down stream processing such as filtration and drying. The crystal morphology can also dictate other quality measures such as size. This paper reviews recent developments in online crystal morphology measurement and control using online imaging and image analysis. Online imaging was found to be able to capture with high fidelity crystal shape and polymorphic transitions in real-time. The images were analysed using a multi-scale image analysis method to extract the crystals from the image background. Preliminary results on estimating crystal growth rates and kinetics parameters for different facets for rod-like crystals were presented. The paper also reviews recent developments in morphological population balance (PB) modelling which can provide the evolution of the shape and distributions of sizes in all crystal face directions in a reactor. Finally, the perspectives for automatic morphology control which require integration of crystal morphology prediction, morphological PB modelling, online 3D imaging and image analysis for shape characterisation as well as computational fluid dynamics are outlined.

Keywords: crystal morphology; shape control; imaging; image analysis; morphological population balance; image processing; multi-scale modelling; pharmaceutical crystals; crystal growth rates; kinetics; computational fluid dynamics; CFD.

DOI: 10.1504/IJMIC.2011.037836

International Journal of Modelling, Identification and Control, 2011 Vol.12 No.1/2, pp.96 - 100

Published online: 21 Mar 2015 *

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