Sterilization of Corticosteroids by 60Co Irradiation

Abstract

Hydrocortisone acetate, isoflupredone acetate, methylprednisolone acetate, and prednisolone hydrous were sterilized by 60Co irradiation. The minimum irradiation dose required for sterilization of corticosteroids was determined from bioburden level and resistance of microorganisms isolated from the manufacturing environment and products to ⁶⁰Co irradiation. The minimum irradiation dose of 1.33 Mrads was determined to provide 10^–6 probability of sterility assurance for corticosteroids. Rales of radiolytic degradation of corticosteroids indicated that potency loss of one percent or less can be expected under the irradiation condition selected Two major types of radiolytic degradation schemes were found to occur by the ⁶⁰Co irradiation of corticosteroids 11 loss of the corticosteroid side chain on the D-ring to produce the C-12 ketone. and 21 conversion of the C-11 alcohol to the C-11 ketone. These compounds are frequently associated in corticosteroids as process impurities or degradation compounds. No new radiolytic compounds unique to 60Co irradiation have been found