Investigation of the hydrocortisone-β-cyclodextrin complex by phase solubility method:: Some theoretical and practical considerations

Phase solubility diagrams (PSDs) and molecular mechanical ( MM) modeling were used to study the complexation of hydrocortisone (HCor) with beta-cyclodextrin (beta-CD). The phase solubility profile of HCor with beta-CD was classified as the B-s-type. PSDs revealed a six-fold increase in HCor water solubility upon addition of 7 mmol center dot dm(-3)beta-CD concentration (solubility in 7 mmol center dot dm(-3) of beta-CD/solubility in water). The thermodynamic study shows the complexation process is exothermic, with a Delta H value of -5.28 kJ center dot mol(-1). MM calculations were used to predict the optimal stoichiometry of the complex formed as well as the possible orientations of HCor inside the beta-CD cavity. The complexes prepared were analyzed through chemical analysis, which provides evidence for the 1:1 complexation of HCor/beta-CD.