COMPLEXATION OF HYDROCORTISONE WITH BETA-CYCLODEXTRIN AND HYDROXYPROPYL-BETA-CYCLODEXTRIN

Hydrocortison (HC) forms water-soluble inclusion compounds with beta-cyclodextrin (beta CD) and hydroxypropyl-beta-cyclodextrin (HP beta CD), as proved by the equilibrium phase solubility diagrams and by H-1-NMR spectroscopy. The solubility isotherm of the HC/beta CD system is of the B-s type, that of the HP beta CD system of the A(L) type. The values of the complex stability constants are K = 4792 M(-1) and 1739 M(-1), respectively. 8 parallel preparations of solid HC/beta CD complexes by coprecipitation resulted in a stoichiometric ratio of 0.49:1 which corresponds to a molar ratio of 1:2; the HC content is 13.2 +/- 0.2%. The ratio of the HC/HP beta CD complex is 0.335 which equals a molar ratio of 1:3; the HC content is 8.6 +/- 0.2%. The proof of inclusion formation was performed by X-ray diffractometry and thermoanalytical procedures (DSC, TG, thermofractography). We cannot exclude that some of the HC molecules are not included in the HPPCD cavity.