Selective crystallisation of a chiral compound-forming system—Solvent screening, SLE determination and process design

A newly developed crystallisation scheme produces single enantiomers from asymmetric mixtures of stereoisomers. The process was modified, adapted and evaluated on bicalutamide, the active pharmaceutical ingredient of the drug Casodex™. A comprehensive solvent/antisolvent screening was carried out based on the COSMO-SAC model and a solvent database of 1432 compounds. Ternary and quaternary phase diagrams of the enantiomers and promising solvent candidates were derived and compared to experimental data. Solid–liquid equilibrium (SLE) model based chiral separation of bicalutamide enantiomers was conducted and the process performance was evaluated in terms of yield and product purity. A concept for internal recycling of process streams enhances the overall yield.