IMPROVEMENT OF SOME PHARMACEUTICAL PROPERTIES OF NOCLOPROST BY BETA-CYCLODEXTRIN AND GAMMA-CYCLODEXTRIN COMPLEXATION

Inclusion complexation of nocloprost, a potent antiulcer prostaglandin derivative, with α-, β-, and γ-cyclodextrins (CyDs) in aqueous solutions has been studied by the solubility method and13C-NMR spectroscopy. The steric requirement of host-guest interaction was reflected in the magnitude of the stability constants and the thermodynamic parameters of the inclusion complexes. Solid complexes of nocloprost with β- and γ-CyDs in a molar ratio of 1 : 2 were obtained on the basis of a Bs-type phase solubility diagram. The X-ray diffraction data suggested that nocloprost is included in the cylindrical channel formed by coaxial alignment of γ-CyD molecules to give a channel type structure. Release and thermal behavior of the solid complexes was examined and compared with nocloprost itself. The results indicated that the β-CyD complex may have great utility among the three CyDs, being a rapid dissolving form of nocloprost with improved thermal stability. © 1990 Kluwer Academic Publishers.