Real-time in situ powder X-ray diffraction monitoring of mechanochemical synthesis of pharmaceutical cocrystals

Angew Chem Int Ed Engl. 2013 Oct 25;52(44):11538-41. doi: 10.1002/anie.201305928. Epub 2013 Sep 23.

Abstract

Looking in: The penetrating power of high-energy X-rays provides a means to monitor in situ and in real time the course of ball-milling reactions of organic pharmaceutical solids by detecting crystalline phases and assessing the evolution of their particle sizes. Upon switching from neat grinding to liquid-assisted grinding, cocrystal formation is enabled or tremendously accelerated, while the reaction mechanism alters its course.

Keywords: X-ray diffraction; cocrystals; mechanochemistry; pharmaceutical materials; reaction monitoring.