Stability studies of amoxicillin/clavulanic acid combination in polyolefin infusion bags

摘要

Study objectives: To study the physical compatibility and chemical stability of amoxicillin, a ?-lactam antibiotic combined with clavulanic acid, a ?-lactamase inhibitor, using a stability-indicating high-performance liquid chromatographic (HPLC) assay. Methods: The study samples were prepared by adding amoxicillin/clavulanic acid to 0.9% sodium chloride solution in polyolefin bags. The contents of the bags were studied after storage under the following conditions: at ambient temperature without protection from light and at 4°C with protection from light for 72 hours. Both compounds were considered stable if they retained >90% of the baseline drug concentration. Three dosages (two adult forms: 2 g/200 mg and 1 g/200 mg, and one paediatric form: 0.5 g/50 mg) were examined under laboratory conditions simulating those used routinely in hospitals. Evaluations for physical compatibility and chemical stability were performed initially and during the storage period. The physical compatibility was assessed using visual observation for signs of discoloration and precipitation at each sampling interval. The optical density was measured to give a measurable reading of the colour; pH values of solutions were also measured. The chemical stability of the drugs was evaluated by using a stability-indicating HPLC assay. Results: When compared with ambient or refrigerated storage conditions, amoxicillin, whatever the studied preparation, was stable for a longer duration than clavulanic acid. The mixture was only stable for four hours at ambient temperature and for eight hours at 4°C. However, we noticed a colour change (from light to dark yellow) of the various reconstituted solutions, undoubtedly because of the pH variations. Conclusion: We recommend that these solutions be kept refrigerated whenever possible.