Recent progress on chiral resolution of pharmaceuticals by crystallization

Chirality is a ubiquitous property in nature and organisms. More than half of the active pharmaceutical ingredients contain at least one chiral center. Because of the stereoselectivity of chiral molecules, the chiral enantiomers often exhibit higher activity with lower side effects than racemates. The precise manufacturing of chiral enantiomer is, therefore, of great significance. At present, chiral resolution of racemate is one of the most efficient and convenient way to harvest enantiomer, whereas chiral resolution by crystallization is of key importance and widely applied technology to obtain pure enantiomer. Here, the recent progress on chiral resolution of pharmaceuticals by crystallization is summarized. Firstly, the history and development of chiral resolution by crystallization is briefly introduced. The enantiomeric resolution approaches based on classical resolution methods(diastereomeric salt resolution and preferential crystallization) and some recent developed novel chiral resolution methods including preferential enrichment and Viedma ripening, as well as their process intensification, are reviewed in detail. Then, other racemate separation methods such as chromatography and membrane separation are also briefly reviewed. Finally, the future study and development on pharmaceutical chiral resolution by crystallization are discussed and prospected. © All Right Reserved.