(287b) Resolution By Crystallization: The Quest for Chiral Purity | AIChE

(287b) Resolution By Crystallization: The Quest for Chiral Purity


Glennon, B., APC Ltd.
Barrett, M., APC Ltd
Pharmaceutically active compounds and their related intermediates are often produced as a mixture of stereoisomers, both as enantiomers and as diastereomers from their achiral raw materials. While stereoisomers of pharmaceutically active compounds bear the same chemical structures, many compounds of altered chirality possess differentiated biological activities. In many cases the desired bioactive stereoisomer (Eutomer) is produced as a mixture of stereoisomers of varied weight %. The concept of stereoisomer resolution is therefore of great interest in the process development and manufacturing of chiral pharmaceutical products.

The present work demonstrates the application of ternary phase diagrams for the early phase process definition and for advanced process understanding of stereoselective crystallization operations. Two case studies will be presented focusing on the initial crystallization design work flow, methodology, theory and engineering details associated with journey towards the resolution of stereoisomers.