title: 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, (13)C-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) A, beta = 95.690(1) degrees and space group P2(1)/c. The form II is orthorhombic: a = 31.252(4), b = 13.052(2), c = 8.0892(11) A 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.
authors.affiliation: Johnson & Johnson, Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Pharmaceutical Sciences Department, Turnhoutseweg 30, B-2340 Beerse, Belgium. hnovoada@prdbe.jnj.com
authors.forename: Héctor Novoa
authors.initials: HN
authors.lastname: de Armas
authors.forename: Oswald M
authors.initials: OM
authors.lastname: Peeters
authors.forename: Norbert
authors.initials: N
authors.lastname: Blaton
authors.forename: Elke
authors.initials: E
authors.lastname: Van Gyseghem
authors.forename: Johan
authors.initials: J
authors.lastname: Martens
authors.forename: Gerrit
authors.initials: G
authors.lastname: Van Haele
authors.forename: Guy
authors.initials: G
authors.lastname: Van Den Mooter
mesh_terms: D003460:Crystallization / Q000379:methods; D011208:Powders / Q000032:analysis / Q000737:chemistry*; D011899:Ranitidine / Q000032:analysis / Q000737:chemistry*; D013237:Stereoisomerism; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D011208:Powders; D011899:Ranitidine