Inclusion complexation of warfarin with cyclodextrins to improve some pharmaceutical characteristics.

Inclusion complexation of warfarin and alpha- or beta-cyclodextrins in water and in the solid phase were studied by a solubility method, a membrane permeation study, thin-layer chromatography, a dissolution study, IR spectroscopy and differential scanning calorimetry. The solubility of warfarin increased with the addition of cyclodextrins. The apparent stability constants of the alpha- and beta-cyclodextrin complexes are 10.29 M-1 and 148.88 M-1, respectively. The greater the stability constant of the inclusion complex the lesser the permeability of warfarin. Solid complexes of warfarin and alpha- or beta-cyclodextrins were obtained by freeze-drying. Clear differences in IR absorption spectra and DSC thermograms were observed between the inclusion complexes and physical mixtures. The dissolution rate of the freeze-dried warfarin-cyclodextrin complexes was increased about 1200-fold and 550-fold for alpha- and beta-cyclodextrins, respectively. The dissolution rate of warfarin was significantly improved by complex formation.