Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487220 | Journal of Pharmaceutical Sciences | 2009 | 13 Pages |
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) Ã
, 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) Ã
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
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Héctor Novoa de Armas, Oswald M. Peeters, Norbert Blaton, Elke Van Gyseghem, Johan Martens, Gerrit Van Haele, Guy Van Den Mooter,