Grant: Strategic Projects - Group

Chirality is a major concern in the modern pharmaceutical, food and agricultural industries. The sale of chiral drugs is close to one-third of all drug sales worldwide. Ordinary chemical production methods for chiral drugs produce a racemic mixture containing enantiomers having identical chemical compositions but different structural orientations in space. It is quite common to find that one isomeric form has a therapeutic effect on the human body while its enantiomer is harmful or ineffective. Hence, there is obvious benefit from separating the two enantiomers to enhance drug's safety and tolerability. The importance of chirally pure drugs has risen dramatically in recent years due to new FDA regulations requiring that chiral drugs be as pure as possible containing a single pure enantiomer.The present research initiative aims to develop reliable, efficient and economic separation routes for industry not only in the early development step of new pharmaceuticals but also in large-scale preparation stage. Specifically, two approaches will be explored: (a) crystallization via diastereomeric salt formation, and (b) hybrid simulated moving bed (SMB) and crystallization process. In the latter approach, a SMB will be used first for enantiomer enrichment beyond the eutectic composition of the SLE diagram followed by direct crystallization to recover pure single enantiomers. Another unique feature of this research work will be to apply the concept of multi-objective optimization in the innovative design and development of the two processes. At current stage it is difficult to foretell which process approach will be cost-effective as SMB requires costly chiral stationary phase while crystallization of diastereomeric salts consumes expensive resolving agent. The techniques to be developed in this research will be generic and could be applied to most chiral systems in the various industries such as food, pharmaceuticals and agricultural. This research would lead to a successful clean and cost-effective processing technology that would create value-added products in the rapidly changing global economy.