Determination of Relative Stability of Urea Complexes from X-Ray Powder Diffraction Data

Abstract

Urea complexes consist of a channel made up of hydrogen-bonded urea host molecules into which a variety of guest molecules can fit to form a crystalline complex. The urea host can accommodate, one at a time, a variety of guests having the requisite size and shape. The stability of the resulting complex is a function of the properties of the guest molecule. A procedure has been devised which produces pure complex free of any uncomplexed urea or host molecules in solution. The insoluble crystalline complexes formed from the solution of urea and guest molecule in methanol established a dynamic equilibrium. When the crystals of complex are removed from the solution, dissociation to urea and guest occurs to an extent, depending upon the dissociation constant of the complex. If the dissociation constant, KD, is very low, undetectable quantities of uncomplexed urea form along with complex. If the dlissoclation constant is high, extensive amounts of urea form in the presence of complex. Characteristic interplanar spacing s are obtained for a urea complex irrespective of the guest molecule present. The pattern obtained for the hexagonal complex is completely different from the pattern obtained for tetragonal urea. X-ray examination of a homologous series of compounds gives, for each partially dissociated complex, spacings for both urea and complex. The relative intensities of urea and complex spacings permit the estimation of the stability of such a complex compared to that of other homologues.

Reduction in Moisture Sensitivity/Uptake of Moisture Sensitive Drugs Through Adduction in Urea

“…The diffractogram of crystals of NRDIC shows peaks at interplanar spacings at 4.15, 3.42, 3.61, and 7.17 Å, which are all characteristic of hexagonal form of urea [39,40]. Absence of major peaks of NRD further indicates that the guest molecules are trapped in the honeycomb network of urea and do not contribute to the crystal structure except for the slight distortions of hexagonal channels caused by bulky guests [41].…”

Urea inclusion compounds of enalapril maleate for the improvement of pharmaceutical characteristics

“…The X-ray powder diffraction pattern confirmed the results of DSC analysis. Diffractional peaks relevant to crystalline enalapril maleate were not detectable in EMIC products, indicating that the guest molecules were trapped and isolated from one another in the honeycomb network of urea and do not contribute to the crystal structure except for slight distortions of the hexagonal channels caused by bulky guests (Radell & Connolly 1961). The diffractogram of hexagonal urea (EMIC; important peaks at interplanar spacings at 4.16 (19%), 3.39 (100%) and 7.36 (5%) Å) (Radell & Connolly 1960;Brodman & Radell 1967) was characteristically distinguishable from that of the pure tetragonal form of urea (mainly characterized by the interplanar spacing at 4.04 (100%) Å) (Radell et al 1964), indicating a change in the crystalline form of urea.…”