Stability of Imipenem-Cilastatin Sodium in AutoDose Infusion System Bags

Abstract

The objective of this study was to evaluate the physical and chemical stability of imipenem-cilastatin sodium 250 mg/100 mL and 500 mg/100 mL (of each drug component) admixed in 0.9% sodium chloride injection packaged in AutoDose Infusion System bags. Triplicate test samples were prepared by bringing the required amount of imipenem-cilastatin sodium injection to volume with 0.9% sodium chloride injection. A total of 100 mL of each of the test solutions was packaged in each of three ethylene vinyl acetate (EVA) AutoDose bags designed for use in the AutoDose Infusion System for each storage condition. Samples were protected from light and evaluated at appropriate intervals for up to three days at 23°C and 14 days at 4°C. Physical stability was assessed using a multistep evaluation procedure that included turbidimetric and particulate measurement in addition to visual inspection. Chemical stability was assessed with stability-indicating high performance liquid chromatography (HPLC) analytical techniques, based on initial drug concentrations and concentrations at appropriate intervals over the study periods. The admixtures were clear throughout the study when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change throughout the study. HPLC analysis revealed extensive decomposition in the samples, with imipenem being the less stable component. The instability of the imipenem-cilastatin sodium admixtures is consistent with previous studies. Admixtures stored under refrigeration should be used immediately upon warming to room temperature due to the rapid rate of imipenem decomposition. The AutoDose Infusion System bags were not found to affect adversely or improve the physical and chemical stability of this drug.