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

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 t...

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Bibliographic Details
Published inChemical communications (Cambridge, England) Vol. 54; no. 32; pp. 4033 - 4036
Main Authors Michalchuk, Adam A L, Hope, Karl S, Kennedy, Stuart R, Blanco, Maria V, Boldyreva, Elena V, Pulham, Colin R
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 2018
Subjects
Ball milling
Comminution
Crystallization
Diffraction
Explosive impact tests
Impact damage
Life Sciences
Moisture content
New technology
Nicotinamide
X ray powder diffraction
ACTIVATION
IMPACT
SPECTROSCOPY
TEMPERATURE
MECHANISM
NICOTINAMIDE
STABILITY
CARBAMAZEPINE
COCRYSTAL
POLYMORPHISM
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Summary: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.
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ISSN:1359-7345
1364-548X
DOI:10.1039/c8cc02187b