Structural characterization of chlorpropamide polymorphs by synchrotron radiation

Campinas

Workshop; Latin American Workshop on Applications of Powder Diffraction; 2007

LNLS

Chlorpropamide (CPD) belongs to the sufonyl urea class of oral hypoglycemics. Five different polymorphs of CPD have been identified to date (I, II, III, IV, V), of which 3 (A,B,C) are most commonly referred to in the published literature [1,3] although with very confuse nomenclature, and only one crystal structure has been determinated [2]. Even after the 3 decades since it was discovered, it is interesting to note that polymorphism in CPD has not been completely characterized. The aim of this study is to characterize the polymorphs of CPD (I(C), II, III,(A) IV) using synchrotron x-ray diffraction and single crystal structure determination (polymorph IV). The samples were characterized using synchrotron radiation x-ray diffraction (LNLS, D10B-XPD beam line), and single crystal diffractometry (Enraf-Nonius Kappa-CCD diffractometer, MoKalpha radiation). The four crystal forms was characterized by synchrotron radiation X-ray diffraction, indexing the pattern and determining the cell parameters. The crystal structure of CPD polymorph IV was determinated by single crystal method (monoclinic system, space group P21, a=6,1110(4), b=8,9340(5), c=12,0100(8), beta=99,577(4)º). The analysis of this structure shows that the molecule presents conformational differences with the orthorrhombic structure of polymorph III [2]. The four CPD polymorphs have different morphological behaviour and present powder x-ray diffraction patterns characteristic of each polymorph that permit a univoque identification of the four crystal forms. The polymorphs III and IV present conformational polymorphism.