Crystallisation of oxcarbazepine form III: emergence of crystals with variable twisted habit

The emergence of crystal structures with twisted morphologies is well-documented [1]. Twisted single crystals have been observed nanoscopically, mesoscopically, and macroscopically and pose challenges with respect to structural characterisation as they lack long-range translational symmetry. Crystal structure prediction (CSP) capabilities can be employed in polymorph screening studies for aiding in the identification of thermodynamically feasible solid forms and assisting experimentalists in performing targeted screening [2,3]. Recent evidence suggests that combining CSP with powder X-ray diffraction data can assist in solving the structure of polymorphic crystals with twisted habit [4].
Oxcarbazepine (OXCBZ) is a commercially available anticonvulsant known to crystallise in at least three polymorphic forms, two of which (form I and form II) have been fully characterised structurally [5]. OXCBZ form III was originally obtained by slow evaporation, at room temperature, from methanol solutions containing additives. Whilst various analytical data were reported, the small size and poor quality of the crystals prevented structure determination. Here, we report experimental protocols for the crystallisation of OXCBZ III from both solution and the vapour phase. Our approach combined CSP studies of the OXCBZ energy landscape with physical vapour deposition and solution-based, automated polymorph screening experiments. Vapour deposition of OXCBZ resulted in the formation of micron-sized needle and fibre-like form III crystals with variable twisted habit. In order to obtain greater insight into these twisted structures, a series of SEM and AFM studies have been performed to develop understanding of their initial formation and evolution over time.