Exploring the polymorphism of sofosbuvir via mechanochemistry: effect of milling jar geometry and material Argyro Chatziadi 1 , Eliška Skořepová 1,3 , Martin Kohout 1 , Luděk Ridvan 2 , Miroslav Šoóš 1 1 Department of Chemical Engineering,University of Chemistry and Technology Prague, Czech Republic, 2 Zentiva, k.s., U kabelovny 130, Czech Republic, 3 Institute of Physics of the Czech Academy of Sciences, Czech Republic Mechanochemistry has been used as a green and sustainable method to explore the polymorphism of several active pharmaceutical ingredients. 1 Until now, many experimental conditions have been investigated to understand how they affect polymorphic transformations, such as the nature and amount of liquid additive 2 and the type and number of milling balls 3 . However, the effect of the properties of the milling jar started to be explored only recently. 4 In this study we investigate and compare the polymorphic transformations of sofosbuvir in stainless steel and polypropylene jars. Interestingly, it is observed that in polypropylene jars, not only the rate of transformation is faster but also the conditions that are developed during these experiments favour the formation of a new form of sofosbuvir, not observed in stainless steel jar experiments. Analysis of the energetics of the system shows that these results are a consequence of the different geometry of the jars and of a significant rise in temperature due to the properties of the material. These findings are an important step toward understanding and even predicting how the choice of jar material affects the kinetics and polymorphic transformation of an active pharmaceutical ingredient during milling. References 1. D. Hasa and W. Jones, Advanced Drug Delivery Reviews , 2017, 117, 147–161. 2. A. Chatziadi, E. Skořepová, J. Rohlíček, M. Dušek, L. Ridvan and M. Šoóš, Crystal Growth and Design , 2020, 20 , 139–147. 3. F. Fischer, N. Fendel, S. Greiser, K. Rademann and F. Emmerling, Organic Process Research & Development , 2017, 21 , 655–659. 4. L. S. Germann, M. Arhangelskis, M. Etter, R. E. Dinnebier and T. Friščić, Chemical Science , 2020, 11 , 10092–10100.
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