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Real-Time In Situ Powder X-ray Diffraction Monitoring of Mechanochemical Synthesis of Pharmaceutical Cocrystals

Authors


  • We acknowledge R. L. Nightingale for equipment design and manufacture, D. S. Bohle for assistance in acquiring single-crystal X-ray diffraction data, A. K. Cheetham for discussions, J. K. M. Sanders for support, Herchel Smith Fund, NanoDTC Cambridge, EPSRC, NSERC Discovery Grant, FRQNT Nouveaux Chercheurs fund for funding, and the Ministry of Science, Education and Sport of the Republic of Croatia (Grant No. 098-0982904-2953).

Abstract

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Looking in: The penetrating power of high-energy X-rays provides a means to monitor in situ and in real time the course of ball-milling reactions of organic pharmaceutical solids by detecting crystalline phases and assessing the evolution of their particle sizes. Upon switching from neat grinding to liquid-assisted grinding, cocrystal formation is enabled or tremendously accelerated, while the reaction mechanism alters its course.

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