X-ray computed tomography for 3D crystallization monitoring: A use case with paracetamol

This work highlights the capabilities and limits of X-ray computed tomography in crystallization monitoring through a use case involving paracetamol as the solute, recrystallized from ethanol, methanol, or a mixture of both. The cooling crystallization operation was set up in two different containers, prepared with cotton yarns stretched vertically, acting as linear nucleation sites that immobilize the grown crystals in the recording area. The largest container (10 mL test tubes) allowed the acquisition of a larger number of crystals (up to 300 particles) for a more appropriate bulk analysis. The smallest container (5 mL pipette tips) allowed for a finer resolution of the recorded solid phase at the expense of a reduced recording volume. Crystallization was monitored in terms of the number of individual crystals, their size, and the overall volume, thus leading to the nucleation and growth rates, and solid-phase production rate. The main benefit of X-ray computed tomography is in the 3D analysis of the reconstructed solid phase. The crystal habit of paracetamol form I was predicted using force-field modeling. The predicted habit was in great accordance with the reconstructed solids, confirming the polymorphic form. Furthermore, face-specific growth rates of reconstructed crystals were measured, paving the way for a novel approach to the investigation of crystal-solvent interactions.