Development of a salt drug with improved solubility: Ethionamide nitrate

• Published in: Journal of molecular structure Vol. 1137; pp. 119 - 125
• Main Authors: Diniz, Luan F., Carvalho, Paulo S., de Melo, Cristiane C., Ellena, Javier
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-06-2017
• Subjects: Active pharmaceutical ingredients; Ethionamide; Solubility; Tuberculosis; Vibrational spectroscopy; X-ray diffraction; X-ray diffraction; Ethionamide; Tuberculosis; Active pharmaceutical ingredients; Solubility; Vibrational spectroscopy
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2017.02.036

To avoid drug resistance, an adequate tuberculosis treatment should include not only a first-line drug but also at least one second-line drug such as, for example, Ethionamide (ETH). However, the dissolution rate and oral absorption of ETH is highly limited by its low aqueous solubility. Considering that a salt is in general more soluble than its parent compound, herein we depicted a new supramolecular modification of ETH, an Ethionamide nitrate salt (ETHNO3). This salt is the first ETH structure that has been crystallized with four independent ionic pairs (ETH+NO3−) in the asymmetric unit. In addition to the structural study, the salt formation was also identified on the FT-IR and FT-Raman spectra. The thermal behavior of ETHNO3 was also investigated here together with its solubility profile in three dissolution media (purified water, pH 4.0 and 7.0).
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