Monoclinic form I of clopidogrel hydrogen sulfate from powder diffraction data

Abstract

The asymmetric unit of the title compound, C16H17ClNO2S+·HSO4 −, (I) [systematic name: (+)-(S)-5-[(2-chloro­phen­yl)(meth­oxy­carbon­yl)meth­yl]-4,5,6,7-tetra­hydro­thieno[3,2-c]pyridin-5-ium hydrogen sulfate], contains two independent cations of clopidogrel and two independent hydrogensulfate anions. The two independent cations are of similar conformation; however, this differs from that observed in ortho­rhom­bic form (II) [Bousquet et al. (2003 ▶). US Patent No. 6 504 030]. The H—N—Cchiral—H fragment shows a trans conformation in both independent cations in (I) and a gauche conformation in (II). In (I), classical inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link two independent cations and two independent anions into an isolated cluster, in which two cations inter­act with one anion only via N—H⋯O hydrogen bonds. Weak inter­molecular C—H⋯O hydrogen bonds further consolidate the crystal packing.

Assessment of analytical techniques for characterization of crystalline clopidogrel forms in patent applications

“…However, these diffraction peaks had less intensity in the diffractogram pattern of PI9911219 ( Figure 7). The diffraction pattern obtained for form I of Clopidogrel bisulfate in the IUCr online database was also very similar to the tested commercial samples and those obtained from Koradia (Chernyshev et al, 2010). This may be attributed to the preferred orientation of crystallites in the samples.…”

“…More recently, the proposed guideline set out by the INPI is a first attempt to harmonize the internal procedures for evaluating the patentability of polymorphic forms in the pharmaceutical area. Upon evaluation of the proposed INPI guidelines, it becomes evident that emphasis has FIGURE 7 -PXRD patterns for form I of clopidogrel bisulfate: a) commercial samples; b) adapted from Koradia, Chawla, Bansal, 2004, c) adapted from PI9911219 - (Bousquet, Castro, Saint-Germain, 2001) and d) adapted from the IUCr database (Chernyshev et al, 2010).…”

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

“…The methyl ester group is, with respect to the plane defined by C(2)–C(3)–N(4) atoms, rotated by about 88° (dihedral angle δ[C(2)–C(3)–C(6)–O(7)]) and oriented away from the bulky scaffold of the molecule ( Figure S1, Supplementary Material ). The solid-state structure was experimentally determined for the salt of clopidogrel with sulfuric acid only [ 17 , 25 ]. Clopidogrel hydrogen sulfate exhibits polymorphism: different polymorphs exist in different conformations [ 17 ].…”

“…The solid-state structure was experimentally determined for the salt of clopidogrel with sulfuric acid only [ 17 , 25 ]. Clopidogrel hydrogen sulfate exhibits polymorphism: different polymorphs exist in different conformations [ 17 ]. The computed gas-phase conformation of clopidogrel is close to the monoclinic form of clopidogrel hydrogen sulfate obtained from powder diffraction data [ 17 ]; see Table 1 .…”

“…Clopidogrel hydrogen sulfate exhibits polymorphism: different polymorphs exist in different conformations [ 17 ]. The computed gas-phase conformation of clopidogrel is close to the monoclinic form of clopidogrel hydrogen sulfate obtained from powder diffraction data [ 17 ]; see Table 1 . The solvent effect practically does not change the spatial structure of the isolated molecule of clopidogrel.…”