Investigation into the Solid and Solution Properties of Known and Novel Polymorphs of the Antimicrobial Molecule Clofazimine


Clofazimine is an anti-mycobacterial agent used as part of a multidrug treatment for leprosy. Recently clofazimine has shown promising activity against multidrug resistant tuberculosis. Clofazimine has been previously known to exist in two different crystal forms, or polymorphs, which are triclinic (F I) and monoclinic (F II) in crystal structure. The thermodynamic relationship between, and the solubility of, these different crystal structures of clofazimine has not previously been characterized. In this work, their solid and solution properties are studied, and as a result, two novel polymorphs of clofazimine (an orthorhombic crystal polymorph and a high temperature polymorph with a monoclinic structure) are reported. The properties of these new solid forms are compared and contrasted with those of the two previously reported polymorphs using thermal, spectroscopic, and microscopic techniques. Molecular modeling studies were also carried out to predict the relative thermodynamic relationship and the crystal morphology of the polymorphs. There was an excellent correlation observed between the aforementioned experimental and molecular modeling results, allowing for the unequivocal determination of the thermodynamic relationship between all four polymorphs of clofazimine

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oai:figshare.com:article/4263320Last time updated on 2/12/2018

This paper was published in FigShare.

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