Pharmaceutical salts of ethionamide with GRAS counter ion donors to enhance the solubility.
Pharmaceutical salts of BCS class II second line anti-tuberculosis drug ethionamide (ETH) with various counter ions namely, 2-chloro-4-nitrobenzoic acid (CNB), 2,6-dihydroxybenzoic acid (2,6HBA), 2,3-dihydroxybenzoic acid (2,3HBA) and 2,4-dinitrobenzoic acid (DNB) were synthesized by crystal engineering approach. All the synthesized salts were characterized by various spectroscopic (NMR, FT-IR,), thermal (DSC & TGA) and PXRD techniques. The crystal structure of the synthesized salts was determined by single-crystal X-ray diffraction techniques. All the reported salts, except ETH-2,3HBA exhibited charge assisted acid pyridine heterosynthon. In ETH-2,3HBA hydoxyl pyridine heterosynthon is observed. In ETH-CNB salt, both ionic and neutral acid pyridine heterosynthon were observed in the asymmetric unit. ETH-DNB salt consists of both partial and complete proton transfer from DNB to ETH in the asymmetric unit. All the synthesized salts were found to be non-hygroscopic at accelerated humid condition (~75% RH). Solubility experiment has been performed in purified water and in 0.1N HCl (pH=1) solution and found that the solubility of ETH-CNB salt was about eight-fold higher soluble than ETH in purified water. The solubility of synthesized salts follows the order of ETH<ETH-2,3HBA<ETH-2,6HBA<ETH-CNB in purified water.
Supramolecular Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka (NITK)-Surathkal, Srinivasnagar 575 025, Karnataka, India.
Sunil Kumar
SK
Nechipadappu
Supramolecular Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka (NITK)-Surathkal, Srinivasnagar 575 025, Karnataka, India. Electronic address: darshak_rtrivedi@yahoo.co.in.
Darshak
D
R Trivedi
D000995:Antitubercular Agents / Q000032:analysis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005000:Ethionamide / Q000032:analysis* / Q000737:chemistry*; D007477:Ions; D012492:Salts; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
D000995:Antitubercular Agents; D007477:Ions; D012492:Salts; D005000:Ethionamide
2,3-Dihydroxybenzoic acid (PubChem CID: 19); 2,4-Dinitrobenzoic acid (PubChem CID: 11,880); 2,6-Dihydroxybenzoic acid (PubChem CID: 9338); 2-Chloro-4-nitrobenzoic acid (PubChem CID: 7448); Crystal engineering; Ethionamide (PubChem CID: 2761171); Molecular complex; Pharmaceutical co-crystal; Pharmaceutical salts; Supramolecular chemistry