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 -