Revealing the early stages of carbamazepine crystallization by cryoTEM and 3D electron diffraction
Edward T. Broadhurst,
Hongyi Xu,
Simon Parsons,
Fabio Nudelman
Affiliations
Edward T. Broadhurst
EaStCHEM School of Chemistry and Centre for Science at Extreme Conditions, The University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3FJ, United Kingdom
Hongyi Xu
Materials and Environmental Chemistry, Stockholm University, Stockholm, SE-106 91, Sweden
Simon Parsons
EaStCHEM School of Chemistry and Centre for Science at Extreme Conditions, The University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3FJ, United Kingdom
Fabio Nudelman
EaStCHEM School of Chemistry and Centre for Science at Extreme Conditions, The University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3FJ, United Kingdom
Time-resolved carbamazepine crystallization from wet ethanol has been monitored using a combination of cryoTEM and 3D electron diffraction. Carbamazepine is shown to crystallize exclusively as a dihydrate after 180 s. When the timescale was reduced to 30 s, three further polymorphs could be identified. At 20 s, the development of early stage carbamazepine dihydrate was observed through phase separation. This work reveals two possible crystallization pathways present in this active pharmaceutical ingredient.
