Pharmaceutical Cocrystals and Salt of Ethionamide with Fluorobenzoic Acids for Improved Drug Delivery

• DOI: 10.1021/acs.cgd.4c01323
• Publication Date: 2024-11-11T15:38:50Z
• Authors: Naveena S. Veeran...; Madhu Rana; Battini Swapna; Raghavaiah Pallepogu; Ashwini K. Nangia
• Keywords: Ethionamide

Ethionamide (ETH) is a second-line antituberculosis drug, but its aqueous solubility poor. A cocrystal/salt screen of ETH with fluorobenzoic acid (FBA) coformers afforded four cocrystals and one salt ETH, namely, ETH-4-fluorobenzoic (4FBA, cocrystal), ETH-3,4-difluorobenzoic (34DFBA, ETH-2,4,5-trifluorobenzoic (245TFBA, ETH-2,3,4,5-tetrafluorobenzoic (2345TFBA, ethionamidium-2-fluoro-6-hydroxybenzoate (2F6HBA, salt). The new crystalline multicomponent cocrystal-salt (MCCS) forms were characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, single crystal FT-IR analysis. Structural analysis showed that the acid-pyridine, hydroxyl-pyridine, thioamide dimer synthons stabilize cocrystals/salt structures. exhibit remarkable improvement in solubility, dissolution, diffusion at pH 7 phosphate buffer solution. ability fluoro compounds to increase membrane bioavailability drugs as MCCS complexes may be general applicability for poor permeability drugs.