Synthesis, characterization and solubility of a new anthelmintic salt: Mebendazole nitrate

Author(s)

Gutierrez, Eduardo L. ^{[1, 2, 3]} ; Souza, Matheus S. ^[1] ; Diniz, Luan F. ^[1] ; Ellena, Javier ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil

^[2] Consejo Nacl Invest Cient & Tecn, INQUISAL, San Luis - Argentina

^[3] Univ Nacl San Luis, Fac Quim Bioquim & Farm, Area Quim Fis, RA-5700 San Luis - Argentina

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1161, p. 113-121, JUN 5 2018.
• Web of Science Citations: 0

Abstract

Salt formation approach was taken to improve Mebendazole (MBZ) solubility. MBZ polymorph A was easily recrystallized as a 1:1 nitrate salt (MBZ N) in methanol. Single crystal X-ray diffraction data show that MBZ N crystallizes in the PT space group. By strong intermolecular H-bonding interactions, MBZ is associated with a nitrate anion forming a supramolecular R-2(2)(8) synthon. Crystal packing is stabilized by these H-bonds, through which each nitrate connects two molecules of MBZ forming chains along the b axis. The vibrational behavior studied by micro FT-Raman and FT-IR spectroscopy is consistent with the crystal structure. Thermal analysis of the salt indicates that the compound is stable up to 150 degrees C, when an almost simultaneous elimination of HNO3 and CO2 occurs. MBZ N equilibrium solubility was evaluated in hydrochloric acid 0.1 M solution and compared with those of MBZ A and C. An improvement in a factor of 5 and 1.22 was found respectively. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 15/25694-0 - Obtaining, characterization and evaluation of novel crystalline solid forms of drugs used treatment of tuberculosis
• Grantee: Luan Farinelli Diniz
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/03487-8 - Center of characterization of new mineral species: Raman spectroscopy, electron microprobe and X-ray and neutron diffraction
• Grantee: Marcelo Barbosa de Andrade
• Support Opportunities: Research Grants - Young Investigators Grants