Ball-free mechanochemistry: in situ real-time monitoring of pharmaceutical co-crystal formation by resonant acoustic mixing

Adam A.L. Michalchuk*, Karl S. Hope, Stuart R. Kennedy, Maria V. Blanco, Elena V. Boldyreva, Colin R. Pulham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Resonant acoustic mixing (RAM) is a new technology designed for intensive mixing of powders that offers the capability to process powders with minimal damage to particles. This feature is particularly important for mixing impact-sensitive materials such as explosives and propellants. While the RAM technique has been extensively employed for the mixing of powders and viscous polymers, comparatively little is known about its use for mechanosynthesis. We present here the first in situ study of RAM-induced co-crystallisation monitored using synchrotron X-ray powder diffraction. The phase profile of the reaction between nicotinamide and carbamazepine in the presence of a small amount of water was monitored at two different relative accelerations of the mixer. In marked contrast to ball-milling techniques, the lack of milling bodies in the RAM experiment does not hinder co-crystallisation of the two starting materials, which occurred readily and was independent of the frequency of oscillation. The reaction could be optimised by enhancing the number of reactive contacts through mixing and comminution. These observations provide new insight into the role of various experimental parameters in conventional mechanochemistry using liquid-assisted grinding techniques.

Original languageEnglish
Pages (from-to)4033-4036
Number of pages4
JournalChemical Communications
Volume54
Issue number32
Early online date28 Mar 2018
DOIs
Publication statusE-pub ahead of print - 28 Mar 2018

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