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Issue 19, 2012
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Crystal engineering approach to improve the solubility of mebendazole

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Abstract

An anthelmintic drug, mebendazole, shows a very low bioavailability (less than 10%) due to its poor aqueous solubility (0.035 mg/mL at 25 °C for form C). To improve its solubility, we combined a group of dicarboxylic acids with mebendazole via liquid-assisted grinding and reaction crystallization methods, and two salts with oxalic and maleic acids, as well as two co-crystals with malonic and glutaric acids, were obtained. These novel multi-component complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses and infrared spectra. The single-crystal structures of mebendazole-maleate salt, mebendazole-glutaric acid co-crystal, and mebendazole-monomethyl oxalate salt, in which one of the carboxyl groups of oxalic acid was esterified during the single-crystal growth in methanol, were determined. It was observed that mebendazole combines dicarboxylic acid/ester via a R22(8) hydrogen-bonding motif that involves a carbamyl benzimidazole and a carboxyl group, resulting in the 1:1 stoichiometry. The powder dissolution studies revealed that the apparent solubility of the complexes was significantly increased after the formation of co-crystals and salts.

Graphical abstract: Crystal engineering approach to improve the solubility of mebendazole

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Article information


Submitted
10 May 2012
Accepted
09 Jul 2012
First published
27 Jul 2012

CrystEngComm, 2012,14, 6221-6229
Article type
Paper

Crystal engineering approach to improve the solubility of mebendazole

J. Chen, Z. Wang, C. Wu, S. Li and T. Lu, CrystEngComm, 2012, 14, 6221
DOI: 10.1039/C2CE25724F

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