Solid State Characterization and Crystal Structure from X-ray Powder Diffraction of Two Polymorphic Forms of Ranitidine Base

Abstract

Ranitidine hydrochloride (RAN-HCl), a known anti-ulcer drug, is the product of reaction between HCl and ranitidine base (RAN-B). RAN-HCl has been extensively studied; however this is not the case of the RAN-B. The solid state characterization of RAN-B polymorphs has been carried out using different analytical techniques (microscopy, thermal analysis, Fourier transform infrared spectrometry in the attenuated total reflection mode, 13C-CPMAS-NMR spectroscopy and X-ray powder diffraction). The crystal structures of RAN-B form I and form II have been determined using conventional X-ray powder diffraction in combination with simulated annealing and whole profile pattern matching, and refined using rigid-body Rietveld refinement. RAN-B form I is a monoclinic polymorph with cell parameters: a=7.317(2), b=9.021(2), c=25.098(6) Å, β=95.690(1)° and space group P21/c. The form II is orthorhombic: a=31.252(4), b=13.052(2), c=8.0892(11) Å with space group Pbca. In RAN-B polymorphs, the nitro group is involved in a strong intramolecular hydrogen bond responsible for the existence of a Z configuration in the enamine portion of the molecules. A tail to tail packing motif can be denoted via intermolecular hydrogen bonds. The crystal structures of RAN-B forms are compared to those of RAN-HCl polymorphs. RAN-B polymorphs are monotropic polymorphic pairs. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:146–158, 2009