INCLUSION COMPLEXATION OF HYDROCORTISONE BUTYRATE WITH CYCLODEXTRINS AND DIMETHYL-BETA-CYCLODEXTRIN IN AQUEOUS-SOLUTION AND IN SOLID-STATE

Inclusion complexation of hydrocortisone butyrate (HB) with alpha-, be ta-, gamma- and dimethyl-beta-cyclodextrins (DM-beta-CyD) in aqueous s olution and in solid state was investigated to examine and compare the interactions of CyDs with HB, which is practically insoluble in water , and to improve solubility and dissolution rate. Complex formation of HB with CyDs in aqueous solution was studied by solubility analysis, circular dichroism, ultraviolet absorption and H-1-NMR spectroscopy. I n the study of solid state interaction of HB with CyDs, equimolar HB-C yD solid complexes were prepared by the solvent evaporation method and complexation was assessed by infrared spectroscopy and thermal analys is. To elucidate the inclusion complexation, the stoichiometric ratio, which was found to be 1:1, apparent stability constants and thermodyn amic parameters for HB-CyD systems were determined. The solubility inc rease of HB in the presence of CyDs in water was in the rank order of DM-beta-CyD much greater than gamma-CyD > beta-CyD > alpha-CyD. The sp ectroscopic data suggested a different inclusion mode of HB within var ious CyD cavities. The dissolution rate of DM-beta-CyD solid complex w as extremely rapid compared with those of alpha-, beta- and gamma-CyD solid complexes.