IUCrJ (Mar 2023)

Formation of ibrutinib solvates: so similar, yet so different

  • Jan Jirát,
  • Jan Rohlíček,
  • Jakub Kaminský,
  • Tomáš Jirkal,
  • Luděk Ridvan,
  • Eliška Skořepová,
  • Vít Zvoníček,
  • Michal Dušek,
  • Miroslav Šoóš

DOI
https://doi.org/10.1107/S2052252523001197
Journal volume & issue
Vol. 10, no. 2
pp. 210 – 219

Abstract

Read online

The transformation processes of non-solvated ibrutinib into a series of halogenated benzene solvates are explored in detail here. The transformation was studied in real time by X-ray powder diffraction in a glass capillary. Crystal structures of chlorobenzene, bromobenzene and iodobenzene solvates are isostructural, whereas the structure of fluorobenzene solvate is different. Four different mechanisms for transformation were discovered despite the similarity in the chemical nature of the solvents and crystal structures of the solvates formed. These mechanisms include direct transformations and transformations with either a crystalline or an amorphous intermediate phase. The binding preference of each solvate in the crystal structure of the solvates was examined in competitive slurry experiments and further confirmed by interaction strength calculations. Overall, the presented system and online X-ray powder diffraction measurement provide unique insights into the formation of solvates.

Keywords