SYNTHESIS AND CHARACTERIZATION OF A NEW MEBENDAZOLE SALT: MEBENDAZOLE HYDROCHLORIDE

E. V. BRUSAU; G. E. CAMÍ; G. E. NARDA; S. CUFFINI; A. P. AYALA; J. ELLENA

JOURNAL OF PHARMACEUTICAL SCIENCES

John Wiley & Sons

Lugar: New Jersey, USA; Año: 2008 vol. 97 p. 542 - 552

0022-3549

ABSTRACT: Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ
HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is  stabilized by the presence of three N–H. . .Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ
HCl indicates that the compound is stable up to 1608C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C.
2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:542–552, 2008Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ
HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is  stabilized by the presence of three N–H. . .Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ
HCl indicates that the compound is stable up to 1608C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C.
2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:542–552, 2008 Keywords: mebendazole hydrochloride; polymorphism; salt formation; crystal structure; FTIR; Raman spectroscopy; thermal stabilitymebendazole hydrochloride; polymorphism; salt formation; crystal structure; FTIR; Raman spectroscopy; thermal stability