Difluprednate: more than meets the eye.

Abstract

Difluprednate, a FDA approved topical corticosteroid indicated for the treatment of inflammation and pain associated with ocular surgery, affords three polymorphic crystal forms (one hexagonal, sg. P65, and two distinct orthorhombic, both sg.'s P212121, phases), whose preparation, thermal stability ranges, crystal structures and stereochemical preferences are here reported. Using DSC, single-crystal structural analysis and less conventional ab-initio X-ray powder diffraction methods, the rich structural and thermal behavior of three difluprednate polymorphs have been clarified, and the validity of previous complex and sometimes contradicting literature reports has been challenged. Complementary solution state NMR provided (1)H, (13)C and (19)F chemical shifts full assignment of the corresponding signals. These results allow us to precisely describe the selective isolation pathways toward three distinct crystal phases, and to define their structural and analytical data necessary for identification and easy and accurate quantification, by modern Rietveld analysis, of complex difluprednate polymorphic mixtures, often obtained as a result of poorly controlled (co)-precipitation methods.

• Authors: Carlotta Giacobbe, Giovanni Palmisano, Giovanni B Giovenzana, Lorella Giovannelli, Roberto Negri, Norberto Masciocchi
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 102 Pg. 305-13 (Jan 2015) ISSN: 1873-264X [Electronic] England
• PMID: 25459928 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Fluprednisolone
• difluprednate

Topics

• Calorimetry, Differential Scanning
• Crystallization
• Fluprednisolone (analogs & derivatives, chemistry)
• Magnetic Resonance Spectroscopy
• X-Ray Diffraction