Rational design, supramolecular synthesis and solid state characterization of two bicomponent solid forms of mebendazole

NARDA, GRISELDA E.; GODOY, AGUSTÍN A.; GUTIÉRREZ, EDUARDO L.; ELLENA, JAVIER

CRYSTENGCOMM

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2020 vol. 22 p. 6559 - 6568

1466-8033

Two novel bicomponent solid forms of mebendazole (MBZ) were developed as a means to modulate itspsychochemical and pharmaceutical properties. Supramolecular synthesis of MBZ A or C with perchloric ormethyl sulfuric acids yields two salts of 1 : 1 stoichiometry, which were analyzed through single crystalX-ray diffraction. MBZ perchlorate crystallizes in the P21/n space group, while MBZ methyl sulfatecrystallizes in the P1¯ space group. The API and its counterions are interconnected in both crystal packingsby an R22(8) supramolecular motif. The 3-dimensional crystal structure is also stabilized by other strongintermolecular hydrogen bonds as well as non-classical interactions. FT-IR spectra are consistent with theinclusion of the anions in the crystal structure. MBZ perchlorate is stable up to 210 °C when it undergoesendothermic loss of the ester moiety. MBZ methyl sulfate is stable up to 160 °C when endothermicelimination of the methylcarbamate moiety occurs. The solubility behavior of MBZ perchlorate, studied byUV-visible spectroscopy, suggests an improvement by a factor of seven with respect to MBZ A, in theapparent solubility of MBZ in 0.1 mol L−1 HCl. Further experiments are required to evaluate both the stabilityof the solids and the maximum solubility of the API.