Solid-state stability and kinetic study of three glucocorticoid hormones: prednisolone, prednisone and cortisone

Abstract

In the class of steroid hormones, glucocorticoids are belonging to the subclass of corticosteroids, consisting of numerous synthetic or naturally occurring compounds, widely used in medical practice either as replacement therapy in glucocorticoid deficiency or to suppress the immune system. Glucocorticoids are active pharmaceutical ingredients used in solid, semisolid or liquid formulations involved mainly in the treatment of different types of cancers, inflammatory and autoimmune disorders, but as well as allergies. Both thermal stability and heterogeneous degradation kinetics of prednisolone, prednisone and cortisone were investigated in dynamic inert atmosphere (dinitrogen), at five heating rates β = 7, 10, 12, 15 and 20 °C min−1 using isoconversional methods of Friedman, Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa, and later the modified non-parametric kinetic (NPK) method. The variation of apparent activation energies versus conversion degree as revealed by isoconversional methods suggested multistep degradation, which was later confirmed by the NPK method. The NPK method disclosed that all three glucocorticoids are degraded by two parallel processes, with apparent activation energies of 171.7 kJ mol−1 for prednisolone, 78.8 kJ mol−1 for prednisone and 61.8 kJ mol−1 for cortisone, respectively. The results are in good agreement with the ones suggested by isoconversional methods, and a discussion regarding the relation between the structure and apparent activation energy is presented.