Effect of Aging on Hydrocortisone—Polyethylene Glycol 4000 and Hydrocortisone—Polyvinylpyrrolidone Dispersions

Abstract

Dispersions containing 40% hydrocortisone were prepared by the solvent method in polyethylene glycol 4000. Dispersions in polyvinylpyrrolidone were prepared by slow evaporation of solvent (type A) and by fast evaporation of solvent (type B). These dispersions were stored at 25°C for 30 d. Plots of time required for 50% (t50%) and 70% (t70%) of the hydrocortisone dispersion to dissolve (beaker method) versus time were obtained. Hydrocortisone-polyethylene glycol showed no apparent significant change in either dissolution rate, X-ray spectra, or scanning electron micrographs. Type A dispersions showed an increase in dissolution rate up to 8 d. Type B dispersions showed an initial decrease followed by an increase in dissolution rate. The initial decrease in dissolution rate of type B dispersions is due to hydrocortisone crystallizing out of the polyvinylpyrrolidone matrix. The increased dissolution for both types of polyvinylpyrrolidone dispersions was not expected and is explained by an increased proportion of the high-energy amorphous component, based on X-ray spectra. Other possibilities such as the presence of polymorphic forms of hydrocortisone and/or reduction in particle aggregation could not be discounted.