Process Integration and Product Enhancement Through Crystal Growth Modifiers

Crystallisation is the most important means of purifying high value chemical products and then delivering them into forms that can be efficiently formulated. Crystal Growth Modifiers (CGM), are molecular analogues of the active ingredient co-generated in synthesis or additives incorporated into the formulation that strongly influence the crystal formation process. In-process CGM have a profound often detrimental influence on process throughput, yield and robusntness of formulations requiring strategies for their removal or moderating their effect. In contrast, control of molecular assembly using CGMs will lead to integration of manufacturing from synthesis to formulation. Rational design of novel CGM as formulation additives can enhance product performance in application and reduce development time.
This project is now delivering new capability for the discovery and characterisation of molecules able to modify the crystal growth of important industrial compounds. The methodology generates face specific crystallographic, particle size and shape information. Novel 3D Crystal Stereo imaging hardware and software developed at the Institute for Process Research and Development at Leeds University has been coupled with the commercial high throughput Crystalline platform provided by Avantium. For the first time, rapid discovery of potent modifiers including early quantification of their impact on process and product performance can be made. A pre-commercial unit has been constructed and is currently being evaluated by the consortium members including Syngenta, Pfizer and Astrazeneca. It is anticipated to launch a commercialised unit in 2013. It is anticipated that the quantitive crystallisation data generated on this equipment will be used in development of modelling technques and informatics for prediction and rationalisation of crystal growth modification through the Synthonic Engineering industrial consortium project led from Leeds.