Abstract

This study develops a spherical crystallization approach using a small amount of water, which avoids adding extra bridging agents. Notably, a new ternary solvate of pantoprazole sodium (PS–BuOH–H2O) was obtained, and its crystal structure was determined by single–crystal X-ray diffraction. The crystal packing and Hirshfeld surface analyses were performed to identify intermolecular interactions within the crystal. In the crystal lattice, water molecules not only coordinate to the sodium ion of pantoprazole sodium but also form a hydrogen bond with n-butanol via O6–H6A···O5. In order to regulate the particle morphology, the effects of crystallization conditions were investigated, including water content, feeding rate of water, solute concentration, temperature, cooling rate, and stirring rate. It was discovered that water plays a key role in promoting the spherical crystallization of PS–BuOH–H2O. In addition, the morphology of the solvate was closely related to the competition process of crystal agglomeration and spherulitic growth. By optimizing the process parameters, well–developed spherical particles could be prepared and stepwise evolution of spherulites via noncrystallographic branching was observed. This study established a water–induced spherical crystallization technique, offering a promising strategy for preparing new crystal forms and improved particle morphology.

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