Crystal and electronic structure of two polymorphic modifications of famotidine. An experimental and theoretical study

The antiulcer agent (i.e. a histamine H-2 receptor antagonist), famotidine is known to crystallize in two polymorphic modifications. A comparison of t he two forms based on single crystal X-ray data and on quantum chemical cal culations is presented. Form A is constructed from molecules with higher in ternal energy. The crystal field together with the intermolecular hydrogen bond network causes important deformation of the molecular charge densities with respect to that of the free molecules. This charge density deformatio n is more pronounced in form A as it is manifested by an increased dipole m oment and by enhanced electrostatic and polarisation interaction energies. Thus the excess internal energy of form A with respect to form B is largely counterbalanced by the increased intermolecular interaction energy in the former modification. (C) 2000 Elsevier Science B.V. All rights reserved.