Long-term Stability of Esomeprazole in 5% Dextrose Infusion Polyolefin Bags at 5 degrees C +/- 3 degrees C after Microwave Freeze-thaw Treatment

Abstract

To improve quality assurance, security, time management, and cost saving of drug delivery, preparation in advance of intravenous solutions has been developed for several infusion solutions. The objective of this study was to investigate the stability of esomeprazole 0.4 mg/mL and 0.8 mg/mL in 5% dextrose polyolefin bags after freezing, long-term storage, and microwave thawing. The stability of five polyolefin bags containing approximately 0.4 mg/mL of esomeprazole and five other bags containing approximately 0.8 mg/mL in 5% dextrose prepared under aseptic conditions was studied after freezing for 1 month at -20 degrees C, thawing in a microwave oven with a validated cycle, and stored at 5 degrees C +/- 3 degrees C. Esomeprazole concentration was measured by high-pressure liquid chromatography using a reversed-phase column C8, a mobile phase consisting of 35% of acetonitrile and 65% of Na2HPO4 buffer at pH 7.59 with HPO4 (2 M) and NaOH (0.5 M), and detection with a diode array detector at 280 nm. Visual, microscopic, and spectrophotometric observation and pH measurements were also performed. No precipitation occurred in the preparations but little change of color was observed. No microaggregate was observed with optical microscopy or revealed by a change of absorbance at 350, 410, and 550 nm. Based on a shelf life of 90% residual potency, esomeprazole solutions (0.4 and 0.8 mg/mL) were stable for at least 20 or 29 days, respectively, after a freezing and microwave thawing period, where 95% one-side lower confidence limit of the concentration-time profile remained superior to 90% of the initial concentration. During this period, the pH values of drug solutions have been observed to decrease without affecting chromatographic parameters. Within these limits, esomeprazole (0.4 and 0.8 mg/mL) in 5% dextrose infusions may be prepared and frozen in advance by a centralized intravenous admixture service, thawed, and stored at least 20 days at 5 degrees C +/- 3 degrees C before use in clinical units.