Photostability and Phototoxicity of Hydrocortisone acetate

Hydrocortisone acetate is a corticosteroid used systemically for the treatment of rheumatoid arthritis, endocrine disorders and allergic diseases, and topically for dermatoses as an antiinflammatory and antiallergic agent. Its sensitivity to UV light has been studied. Hydrocortisone is rather stable under UVA light (2.5% and 1.5% lysis in PBS and in MeOH, respectively, under 30 J/cm2), but it readily decomposes under 15 J/cm2 of UVB light (70% in PBS, 57% in MeOH, 40% in the solid state and 20% in a commercially available cream). Two main photoproducts have been isolated and characterized. They correspond to the 18 and 18-CH3 diastereoisomers formed by loss of 17--ketol side chain (necessary for glucocorticoid activity) followed by the 17-OH oxidation to keto-group. Moreover, Hydrocortisone showed photohemolytic properties under UVB light, partly dependent on the presence of oxygen and mostly on the radical species and stable photoproducts formed during irradiation. No phototoxicity was found under UVA light. Therefore, hydrocortisone acetate must be protected from light during storage and administration to avoid both the phototoxic effects and the reduction of therapeutic activity.