RESUMO
The purpose of this study is to determine the effect of terminal sterilization by gamma irradiation on 500-mL amber Type I and Type III glass containers (bottles) containing oxytetracycline (OTC) (25% W/V) suspension formulated using 20% (W/V) phospholipids syrup. The formulation was developed for veterinary parenteral administration. The results of terminal sterilization were used to assess the acceptability for this suspension product. OTC is light-sensitive and needs to be stored in amber glass containers. Amber Type I and Type III glass containers were considered for this formulation during development. Type I is a highly resistant, borosilicate glass (oxidized glass). Type III, which is soda-lime glass (reduced glass, see Materials and Methods), may also be used for parenteral products. The amber Type I and Type III glass containers, containing the suspension, were irradiated at 20-40 kGy for 150 min. In order to determine the sterility of the suspension, ampoules of the biological indicator, Bacillus pumilus, were placed in a number of bottles of the suspension. The bottles with the biological indicators were then positioned among the rest of the production bottles as per a radiation dose-mapping study conducted at the sterilization facility. Potency determination and stability evaluations for OTC were performed using high pressure liquid chromatography (HPLC). The results indicate that the gamma irradiation dose of 20-40 kGy for 150 min was able to inactivate 10(6) Bacillus pumilus spores in ampoules. After gamma sterilization, OTC concentration, pH, particle size, endotoxins, and sterility were evaluated. The assay results were comparable for the suspension in amber Type I and Type III glass containers. Sterility and pyrogenicity were measured by the USP Membrane Filtration Method and USP Bacterial Endotoxins Test, respectively. The suspension in the amber Type III glass container was also chemically (HPLC) and physically (suspension mean particle size, viscosity, density, and syringeability) stable for at least 12 months at room temperature. However, amber Type I glass darkened following irradiation, leading to a substantial reduction in glass transparency. The appearance of amber Type III glass was acceptable. Thus, the "reduced" glass, such as soda-lime, was found to be much less susceptible to darkening than the highly oxidized borosilicate amber. Due to the potential aesthetic concerns with Type I glass, the amber Type III glass container was selected for this suspension formulation.