Research output: Contribution to journal › Article › peer-review
Ball-free mechanochemistry:: In situ real-time monitoring of pharmaceutical co-crystal formation by resonant acoustic mixing. / Michalchuk, Adam A.L.; Hope, Karl S.; Kennedy, Stuart R. et al.
In: Chemical Communications, Vol. 54, No. 32, 18.04.2018, p. 4033-4036.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Ball-free mechanochemistry:: In situ real-time monitoring of pharmaceutical co-crystal formation by resonant acoustic mixing
AU - Michalchuk, Adam A.L.
AU - Hope, Karl S.
AU - Kennedy, Stuart R.
AU - Blanco, Maria V.
AU - Boldyreva, Elena V.
AU - Pulham, Colin R.
N1 - Publisher Copyright: © The Royal Society of Chemistry 2018.
PY - 2018/4/18
Y1 - 2018/4/18
N2 - 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.
AB - 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.
KW - COCRYSTAL
KW - CARBAMAZEPINE
KW - SPECTROSCOPY
KW - NICOTINAMIDE
KW - POLYMORPHISM
KW - TEMPERATURE
KW - ACTIVATION
KW - STABILITY
KW - MECHANISM
KW - IMPACT
UR - http://www.scopus.com/inward/record.url?scp=85045576903&partnerID=8YFLogxK
U2 - 10.1039/c8cc02187b
DO - 10.1039/c8cc02187b
M3 - Article
C2 - 29619475
AN - SCOPUS:85045576903
VL - 54
SP - 4033
EP - 4036
JO - Chemical Communications
JF - Chemical Communications
SN - 1359-7345
IS - 32
ER -
ID: 12669471