title: Physicochemical characterization of deflazacort: thermal analysis, crystallographic and spectroscopic study.
abstract: The solid state properties of deflazacort (1-(1beta,16alpha)-21-(acetyloxy)-11-hydroxy-2'-methyl-5'H-pregna-1,4-dieno[17,16-d]oxazole-3,20-dione, 1) were investigated using differential scanning calorimetry (DSC), thermogravimetry (TG), single-crystal X-ray diffraction, solid and liquid nuclear magnetic resonance spectroscopy ((13)C NMR), Fourier transform infrared and Raman spectroscopy (FTIR and FT Raman). From the trends observed in the crystal structure and spectral data some conclusions can be made about hydrogen bonding, molecular conformation and crystal packing. Compound 1 crystallizes in an orthorhombic cell, space group P2(1)2(1)2(1) and the following lattice parameters: a=11.2300(5), b=12.8161(8), c=16.171(1)A, V: 2327.4(2)A(3), D(c): 1.260g/cm(3), R1=0.0479, wR2=0.1012. The crystal structure is stabilized by intra and intermolecular interactions, which provides for a very closely packed form. The NMR data indicated that 1 shows a similar conformation in solid and liquid state; while, thermal data revealed that 1 follows a monophasic pattern with a DSC melting peak at 258.4 degrees C (DeltaH 99.7Jg(-1), n=3), indicating that 1 is thermally stable as solid; but, as liquid is unstable to undergo a thermal decomposition reaction. The reactivity of 1 toward light and moisture was examined via DSC and TLC. The data indicated that 1 do not interact with water to give hydrated forms or decomposition products; however, light degrades 1.
authors.affiliation: Agencia Córdoba Ciencia, CEPROCOR, Córdoba, Argentina.
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Cuffini
authors.forename: Javier F
authors.initials: JF
authors.lastname: Ellena
authors.forename: Yvonne P
authors.initials: YP
authors.lastname: Mascarenhas
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Ayala
authors.forename: Heinz W
authors.initials: HW
authors.lastname: Sielser
authors.forename: Josué Mendes
authors.initials: JM
authors.lastname: Filho
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Monti
authors.forename: Virginia
authors.initials: V
authors.lastname: Aiassa
authors.forename: Norma R
authors.initials: NR
authors.lastname: Sperandeo
mesh_terms: D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D006358:Hot Temperature; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D011282:Pregnenediones / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013818:Thermogravimetry; D014466:Ultraviolet Rays
chemical_list: D011282:Pregnenediones; C021988:deflazacort