Listening to the Formation of Polymorphs in a Ball Mill.

In this contribution, we apply our newly developed ball-milling platform, which combines Raman spectroscopy and thermal (IR) imaging, as well as acoustic and high-speed optical video recordings, to the synthesis and transformation of citric acid-isonicotinamide (1:2) cocrystal polymorphs in transparent PMMA jars. Particularly, we demonstrate how Raman, temperature, acoustic, and video data are complementary and enable detection and connection of chemical and physical events happening during ball-milling in a time-resolved manner. Importantly, we show that the formation of the three cocrystal polymorphs can be detected through acoustic analyses solely.