E. Maccaroni, L. Malpezzi, W. Panzeri
Sep 21, 2010
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Influential Citations
5
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Journal
Journal of pharmaceutical and biomedical analysis
Abstract
Two polymorphic forms of benfluorex hydrochloride, phases I and II, were isolated as monophasic polycrystalline samples, and structurally characterized using ab initio X-ray powder diffraction methods and a global optimization strategy (simulated annealing). Form I crystallizes in monoclinic system, space group P2(1)/n, with Z=4, a=21.0719(10)A, b=7.0563(4)A, c=14.8684(7)A, beta=116.998(3) degrees , V=1969.8(2)A(3), while Form II crystallizes in the orthorhombic space group Pbca, with Z=8, a=33.8031(2)A, b=15.1451(8)A, c=7.6138(6)A, V=3897.9(4)A(3). Crystals of Form I and Form II of benfluorex hydrochloride are based upon an ionic packing of protonated benfluorex molecules at the most basic site, the N1 atoms, and chloride anions. Form I shows the presence of mu-Cl ions, generating centrosymmetric dimers with a N(2)Cl(2) moiety, while Form II contains antiparallel chains of C-H...O hydrogen-bonded molecules running along c axis. DSC and thermodiffractometric measurements showed that heating progressively Form II from ambient temperature to 160 degrees C causes a phase transition to the thermodynamically stable Form I, immediately followed by the sample melting, near 165 degrees C. Recrystallization directly to Form I is observed when the melt is cooled back to ambient temperature, with a significant hysteresis (this event being centered near 130 degrees C).