ESR Study Applied To Thermal Stability Of Radiation-Induced Species Of Solid Ketoprofen

Ketoprofen [2-(3-benzoylphenyl) propionic acid] is a non-steroidal anti-inflammatory drug. It has been widely used in human and veterinary medicine. Radiation processing of drugs and its ingredients is recognized as a safe and effective method among the existing technologies for sterilization and protocols that can be found in ISO 11137-1. Radiosterilization of drugs or other medical products by a suitable dose of ionizing radiation conducted in an appropriate environment ensures sterile conditions by destroying or removing vegetative and sporulating microbes from the ingredients or environment. In earlier studies the effects of gamma radiation was evaluated by selected physico-chemical methods and the observations showed that solid ketoprofen is relatively stable toward ionizing irradiation and that radiosterilization might be a suitable method for the sterilization of solid ketoprofen. The studies reported in this work were undertaken to analyse thermal stability of free radicals by accelerated aging method with a view to the determination of shelf-life. The expiration date (shelf-life) of a product is based on evaluation of both, thermal stability of free radicals, as well as on the time evolution of stable radiolysis products. Namely, storage time is determined by the time required by any degradation product in the dosage form to achieve a sufficient level to represent a risk to the patient. This work shows that ESR spectroscopy provides means for determination of thermal stability of radicals induced by gamma-irradiation in solid drugs. Therefore, despite the complex mixture of individual free radicals induced by gamma-irradiation in solid ketoprofen, the overall lifetime of free radicals could be determined by using isothermal and isochronal annealing. This study shows that radicals induced by gamma-irradiation in solid ketoprofen are stable for at least about 6 months. (author).