Industrial Crystallisation Fundamentals

The trend towards more complex molecules, materials and systems will proceed into the future bringing new crystallisation challenges for particulate products such as pharmaceuticals. The solution to these challenges lies in a fundamental understanding of the crystallisation sub-processes such as crystal nucleation and growth onto which we can build innovative, integrated and intensified continuous crystallisation processes.
One long standing and industrially important issue is the control of crystal nucleation in terms of form and rate [1]. Small scale crystallisation experiments indicate that a single nucleus mechanism is occurring. A general occurrence of such a mechanism would have large implications for product quality control of industrial crystallizers. The mechanism explains the large induction time distributions observed on a small scale and enables nucleation rate measurements. These measurements show that the kinetic pre-exponential factor of the nucleation rate equation is lower than theoretically expected which would indicate that either the concentration of heterogeneous particles or the attachment frequency of building units is lower than expected.
In Situ Product Removal (ISPR) in bio-based processes in principle leads to high productivities due to the elimination of toxic and inhibiting effects of the product towards the bio-catalysts (micro-organisms, enzymes). ISPR by crystallisation has the potential to significantly improve the efficiency of bio-based processes and to simplify downstream separation and purification of the product. I will show that multicomponent solids such as co-crystals facilitate ISPR under conditions where crystallisation of the pure component is not possible [2].

References
1. R.J. Davey, S.L.M. Schroeder, J.H. ter Horst, Nucleation of Organic Crystals – A Molecular Perspective, Angewandte Chemie 52 (2013) 2166.
2. J. Urbanus, C.P.M. Roelands, J. Mazurek, D. Verdoes, J.H. ter Horst, Electrochemically induced co-crystallization for product removal, CrystEngComm 13 (2011) 2817-2819.