TY - JOUR
T1 - Investigation into the Solid and Solution Properties of Known and Novel Polymorphs of the Antimicrobial Molecule Clofazimine
AU - Bannigan, Pauric
AU - Zeglinski, Jacek
AU - Lusi, Matteo
AU - O'Brien, John
AU - Hudson, Sarah P.
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/12/7
Y1 - 2016/12/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85002561087&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.6b01411
DO - 10.1021/acs.cgd.6b01411
M3 - Article
AN - SCOPUS:85002561087
SN - 1528-7483
VL - 16
SP - 7240
EP - 7250
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 12
ER -