The Action “Development of novel rapid design methods for separation of enantiomers by crystallization: a process systems engineering approach” looks at how process systems engineering can be exploited to obtain enantio-pure crystals in desired particle size effectively and safely. The enantio-purity became a critical pharmaceutical issue after the Thalidomide crisis, when one enantiomer of the molecule delivered the desired physiological effect, whereas the counter-enantiomer caused severe birth defects, impacting tens of thousands of pregnancies. The size of particles matters because different particle sizes dissolve at different rates (think of the powder and crystalline sugar). This is a critical property of drug products: during a heart attack, one wants immediate, short-term effects, but after a dentist’s visit, one may choose to take a painkiller that will last for hours.
There are numerous techniques to obtain enantiopure products, which can be divided into two major groups: stereoselective synthesis, in other words, choosing chemical reactions that will selectively produce the desired enantiomer, or separate enantiomers from their mixtures. Separations are usually realized by diastereomer salt formation, crystallization, and chromatography. The particle size can be adjusted in the crystallization, and secondary correction operations such as granulation or milling can also be employed. This research aimed to combine the separation of the enantiomers with controlled particle formation innovatively and effectively, which cuts costs, shortens manufacturing technology and improves overall safety. This is important as solving the issues can bring affordable medicines closer to us and those in need. This project targets a class of materials, so-called conglomerates, which has the property that enantiopure crystals are being formed. Crystallizing selectively one or the other enantiomer is called preferential crystallization (PC). This project looks at how PC can be optimized and designed rapidly, with minimal or without preliminary information about the crystallization behavior of the compound of interest.
The formal objectives of this Marie Skłodowska Curie Action (MSCA) have been to (a) apply crystallization systems engineering to enhance the preferential crystallization of enantiomers; (b) develop detailed population balance-based process models for PC in batch and continuous mode and apply multi-objective optimizations to find the best operating conditions and (c) apply data mining and machine learning on the simulated data to obtain shortcut design methods. A parallel goal of the MSCA Individual Fellowship is to foster the development of the individual researcher and support the integration into the local academic system.
