Effects of freezing, long-term storage, and microwave thawing on the stability of piperacillin plus tazobactam in 5% dextrose for infusion

Background: A combination of piperacillin with tazobactam is often administered to hospital patients by infusion. Advance preparation of IV solutions of these drugs could be an efficient way to improve the quality, time management, and cost associated with drug delivery, but little is known about the stability of these drugs after freezing followed by microwave thawing. Objective: The purpose of the study was to investigate how a process of freezing, long-term storage, and microwave thawing affects the stability of piperacillin with tazobactam in 5% dextrose for infusion. Methods: Five replicates of a mixtures of 4 g piperacillin and 0.5 g tazobactam in 20 mL of water plus 100 mL of 5% dextrose were prepared and stored in polyvinyl chloride (PVC) bags. The stability of the mixtures was studied after freezing for 3 months at -20°C followed by thawing in a microwave oven and additional storage at 4°C for up to 60 days. The concentrations of piperacillin and tazobactam in each sample were measured by high-pressure liquid chromatography. The samples were inspected visually, and pH was measured. Results: After 3 months of storage at -20°C, microwave thawing, and 35 days of storage at 4°C, more than 90% of the initial concentration of both piperacillin and tazobactam remained. At this point, the lower 95% confidence limit of the best-fit line by linear regression of percent remaining was 90.1% for piperacillin and 90.3% for tazobactam. The pH decreased by 1.16 units over 35 days of storage at 4°C, but no colour change of precipitation was observed. From 35 to 60 days, the concentrations of both piperacillin and tazobactam fell below the acceptable limit and pH values continued to decrease slightly. Conclusions: The combination of piperacillin (4 g/120 mL) and tazobactam (0.5 g/120 mL) in 5% dextrose stored in PVC bags, frozen for 3 months at -20°C, thawed in a microwave oven, and then stored at 4°C for an additional 35 days retained more than 90% of the initial concentration of each drug. This should allow for advance preparation of this drug combination.