Shelf lives of aseptically prepared medicines—Stability of piperacillin/tazobactam in PVC and non-PVC bags

Abstract

Parenteral aseptic preparations of piperacillin/tazobactam are used frequently in hospitals, but there is limited published information on their stability in polyvinyl chloride (PVC) and polyolefine laminate (non-PVC). The purpose of this study was to evaluate the stability in these containers and to determine the optimum validated shelf life so that the formulations may be prepared in bulk in appropriately licensed facilities. In the first study, the stability of piperacillin/tazobactam 45 mg/ml was determined in polyvinyl chloride and polyolefine laminate bags in 0.9% (w/v) sodium chloride at 7 °C, 25 °C/60% relative humidity (RH) and room temperature in the light (RTL) with storage up to 41 days for PVC bags and 98 days for non-PVC bags. In the second study, the stability of piperacillin/tazobactam 45 mg/ml was determined in non-PVC bags in a buffered sodium chloride formulation at 7 °C, 25 °C/60% RH and RTL with storage up to 201 days. Samples from each admixture were analysed for piperacillin concentration, tazobactam concentration and appearance of decomposition products by stability indicating high-performance liquid chromatography (HPLC). The pH and appearance of solution and container were also monitored. Shelf lives were calculated using the maximum rate method. Tazocin™ was found to be stable in 0.9% (w/v) sodium chloride in PVC bags for up to 5 days at 7 °C and 4 days at both 25 °C and RTL. In non-PVC bags, it was stable for 17, 4 and 3 days, respectively. It was stable in the buffered sodium chloride formulation in non-PVC bags for up to 58 days at 7 °C, 10 days at 25 °C and 7 days at RTL.