Stability of doripenem in polyvinyl chloride bags and elastomeric pumps

Abstract

The stability of doripenem 500 and 1000 mg in polyvinyl chloride (PVC) bags and elastomeric pumps at various storage temperatures was evaluated. Commercially available doripenem vials were reconstituted and mixed with either 0.9% sodium chloride injection or 5% dextrose injection to produce 100-mL solutions with concentrations of 5 and 10 mg/mL. Six replicate solutions in either PVC bags or elastomeric pumps were prepared. Bags were sampled immediately after preparation and stored at 25 degrees C, 4 degrees C, or -20 degrees C. Those stored at 25 degrees C were sampled for an additional 48 hours, and bags stored at 4 degrees C were sampled for 12 days. Bags frozen at -20 degrees C for 14-28 days were allowed to thaw at either 25 degrees C for 4-6 hours or 4 degrees C for 24 hours and sampled for an additional 48 hours. Solutions retaining > or =90% of the initial concentration were considered stable. At 25 degrees C, both concentrations were stable for 24 hours in 0.9% sodium chloride injection and for 16 hours in 5% dextrose injection. At 4 degrees C, 5-mg/mL solutions were stable for 10 days in both 0.9% sodium chloride injection and 5% dextrose injection, while 10-mg/mL solutions were stable for 10 days in 0.9% sodium chloride injection and 7 days in 5% dextrose injection. A white precipitate, which returned to solution by shaking, was noted after thawing the frozen containers. Whether thawed at 4 degrees C or 25 degrees C, both 5- and 10-mg/mL solutions were stable for 16 hours at 25 degrees C. Doripenem 5- and 10-mg/mL solutions were stable for 24 hours at 25 degrees C when diluted in 0.9% sodium chloride injection. When diluted in 5% dextrose injection, the stability of both concentrations of doripenem decreased to 16 hours at 25 degrees C. When stored at 4 degrees C, 5-mg/mL solutions in either 0.9% sodium chloride or 5% dextrose injection were stable for at least 10 days, and all solutions containing doripenem 10 mg/mL were stable for at least 7 days. Both concentrations of doripenem were stable for 16 hours when previously frozen and thawed at 25 degrees C and 4 degrees C. The rate of doripenem degradation was similar between PVC and elastomeric containers.