A new polymorph of the gastrokinetic drug cisapride monohydrate.

ABSTRACT

Cisapride monohydrate (systematic name 4-amino-5-chloro-N-{(3RS,4SR)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl}-2-methoxybenzamide monohydrate), C23H29ClFN3O4·H2O, is a nondopamine-blocking gastrokinetic drug. A new polymorph of cisapride monohydrate has been reported nearly three decades after the report of its first known crystal structure [Collin et al. (1989). J. Mol. Struct. 214, 159-175]. The second polymorph is also monoclinic, but with different unit-cell parameters. A comparison of both polymorphic forms shows that the difference is thus not in the molecular conformation but in the arrangements of molecules in the crystal packing. The crystal morphology of two forms was predicted with the BFDH model in Materials Studio and inferred that the powder of the new polymorph has better flowability than the original polymorph. The results of DSC (differential scanning calorimetry) analysis and slurry experiments show that both polymorphs are stable at room temperature.