Influence of ionizing radiation on the stability of clarithromycin antibiotics

Highlights: • This is the first report to the best of our knowledge of study of effect ionizing radiation of clarithromycin. • The analysis by HPLC confirms the stability of drug strength CLA at 2, 5 and 25 kGy and no degradation products were observed. • The analysis of impurities by HPLC after irradiation at 5 kGy showed an acceptable impurity level. • An unacceptable increase of single impurity was evidenced after irradiation at 25 kGy. Therefore, CLA is radiosensitive. - Abstract: The growing interest centered on treatment of pharmaceuticals by ionizing radiation arises from the clear advantages this process offers compared to other methods of sterilization. In this study, the effect of ionizing radiation on clarithromycin (CLA) powder commercially named Zeclar® was investigated. The analysis by HPLC confirms the stability of Zeclar® potency at 2, 5 and 25 kGy and no degradation products were observed. The anti-microbial assays revealed that the activity of irradiated clarithromycin at 2 and 5 kGy did not reduce against Staphylococus aureus ATCC 6538, Streptocoque B (Streptococcus agalactiae) Enterococcus feacium ATCC 19434 and Helicobacter pylori ATCC 43504 and stable during 30 days storage period. However, at 25 kGy, the antimicrobial activity of CLA was significantly reduced. The analysis of impurities by HPLC after irradiation at 5 kGy showed an acceptable impurity level as the content limit described by the European and United States Pharmacopeia. On the contrary, an unacceptable increase of single impurity was evidenced after irradiation at 25 kGy. Therefore, CLA is radiosensitive. After gamma irradiation, complex EPR lines were recorded confirming the presence of a large number of free radicals formed during the irradiation. Approximately 61 days after the irradiation of Zeclar®, the radical concentration decreased by 85% % and 95% respectively for 5 and 2 kGy. Numerical analysis of the time dependence of the integral amplitude of the measured EPR lines demonstrated good agreements between the experimental points and the properly fitted exponential first order function.