Ranitidine hydrochloride, a polymorphic crystal form

Abstract

In the title compound, dimethyl(¿5-[2-(1-methylamino-2-nitroethenylamino)ethylthiometh yl]-2- furyl¿methyl)ammonium chloride, C(13)H(23)N(4)O(3)S(+).Cl(-), protonation occurs at the dimethylamino N atom. The ranitidine molecule adopts an eclipsed conformation. Bond lengths indicate extensive electron delocalization in the N,N'-dimethyl-2-nitro-1, 1-ethenediamine system of the molecule. The nitro and methylamino groups are trans across the side chain C=C double bond, while the ethylamino and nitro groups are cis. The Cl(-) ions link molecules through hydrogen bonds.

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

“…The enamine portion of the ranitidine molecule can exist in two possible configurations with respect to the double bond C11–C13 ( E and Z arrangements), in which the methylamino and the nitro substituents are cis and trans to each other, respectively. The Z configuration was adopted in both structures of RAN‐B polymorphs, as in the crystal structure of RAN‐HCl form I 13. This arrangement in the crystal structure is different to that of the ranitidine hydrogen oxalate26 that displays the E configuration.…”

“…RAN‐HCl form I crystal structure13 was solved using single crystal X‐ray diffraction at low temperature ( T = 100 K), in order to reduce the disorder in the tail of the molecule. The first known crystal structure of a RAN‐HCl polymorph was solved by single crystal X‐ray diffraction for the form II polymorph 14.…”

Disappearing Polymorphs Revisited

“…10 The crystal structures of both forms have been subsequently determined; both forms crystallize in the monoclinic P 2 1 / n , space group, wherein the nitroethenediamine moiety of the ranitidine cations displays different conformations and degrees of disorder (Figure 1 c ). 26 – 28 This is thus also an example of conformational polymorphism . 29 …”

Relationship between crystal structure and mechanical properties of ranitidine hydrochloride polymorphs

“…This is in accordance with previous reports on contribution of slip planes to compressibility. [3][4][5][6][7][8][9] IMC a possesses closed crystal packing (higher true density; 1.42 g mL 21 ) and demonstrated better compactibility than IMC c. Overall tabletability of IMC a was found to be better, pointing towards contribution of compactibility to overall tabletability.…”