TY - JOUR
T1 - Structures from powders
T2 - Diflorasone diacetate
AU - Maccaroni, Elisabetta
AU - Giovenzana, Giovanni Battista
AU - Palmisano, Giovanni
AU - Botta, Daniela
AU - Volante, Paolo
AU - Masciocchi, Norberto
PY - 2009/1
Y1 - 2009/1
N2 - Diflorasone diacetate, a steroid anti-inflammatory drug (marketed as Diacort® or Florone® by Pfizer) and used in the treatment of skin disorders, can be prepared as anhydrous form, DD1 (as deposited in the US pharmacopoeia), or as a monohydrated phase, DDW. Heating the DDW form above 90 °C, a mixture of DD1 and of a new anhydrous polymorph, DD2 is obtained. Further heating of this mixture, or of pure DD1, up to 230 °C (only a few degrees before melting!), generates an elusive anhydrous DD3 polymorph. Their crystal structures, determined uniquely from laboratory powder diffraction data, show the isomorphous character of the DDW and DD1 forms, while the DD2 and DD3 polymorphs crystallize with markedly different unit cells. Crystals of the DD1, DD2 and DDW forms are orthorhombic, P212121, a = 29.386(1) Å; b = 10.4310(9) Å, c = 8.1422(7) Å, V = 2495.8(3) Å3 for DD1; a = 15.2639(10) Å; b = 11.7506(7) Å, c = 13.8931(11) Å, V = 2491.9(3) Å3 for DD2; a = 30.311(2) Å; b = 10.6150(9) Å, c = 7.9337(7) Å, V = 2552.7(4) Å3 for DDW; while the lattice parameters for the monoclinic P21 DD3 species are a = 11.5276(10) Å; b = 13.8135(11) Å, c = 7.8973(7) Å, β = 103.053(6)°, V = 1225.0(2) Å3. These compounds have also been fully characterized by thermo analytical methods, as well by 13C, 19F, and 1H NMR spectroscopy.
AB - Diflorasone diacetate, a steroid anti-inflammatory drug (marketed as Diacort® or Florone® by Pfizer) and used in the treatment of skin disorders, can be prepared as anhydrous form, DD1 (as deposited in the US pharmacopoeia), or as a monohydrated phase, DDW. Heating the DDW form above 90 °C, a mixture of DD1 and of a new anhydrous polymorph, DD2 is obtained. Further heating of this mixture, or of pure DD1, up to 230 °C (only a few degrees before melting!), generates an elusive anhydrous DD3 polymorph. Their crystal structures, determined uniquely from laboratory powder diffraction data, show the isomorphous character of the DDW and DD1 forms, while the DD2 and DD3 polymorphs crystallize with markedly different unit cells. Crystals of the DD1, DD2 and DDW forms are orthorhombic, P212121, a = 29.386(1) Å; b = 10.4310(9) Å, c = 8.1422(7) Å, V = 2495.8(3) Å3 for DD1; a = 15.2639(10) Å; b = 11.7506(7) Å, c = 13.8931(11) Å, V = 2491.9(3) Å3 for DD2; a = 30.311(2) Å; b = 10.6150(9) Å, c = 7.9337(7) Å, V = 2552.7(4) Å3 for DDW; while the lattice parameters for the monoclinic P21 DD3 species are a = 11.5276(10) Å; b = 13.8135(11) Å, c = 7.8973(7) Å, β = 103.053(6)°, V = 1225.0(2) Å3. These compounds have also been fully characterized by thermo analytical methods, as well by 13C, 19F, and 1H NMR spectroscopy.
KW - Solvates
KW - Structure determination
KW - Topical corticosteroid
KW - X-ray powder diffraction
UR - http://www.scopus.com/inward/record.url?scp=57249108192&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2008.09.014
DO - 10.1016/j.steroids.2008.09.014
M3 - Article
SN - 0039-128X
VL - 74
SP - 102
EP - 111
JO - Steroids
JF - Steroids
IS - 1
ER -