Effect of Freezing, Long-Term Storage, and Microwave Thawing on the Stability of Ketorolac Tromethamine

Abstract

BACKGROUND: Ketorolac tromethamine is a nonsteroidal agent with potent analgesic and moderate antiinflammatory activity. Advance preparation of intravenous solution could be useful to improve quality assurance, time management, and cost-savings of drug delivery. Objective: To investigate the effect of freezing, long-term storage, and microwave thawing on the stability of ketorolac tromethamine in dextrose 5% infusion. METHODS: Five polyolefin bags of solution containing ketorolac tromethamine 20 mg per 100 mL of dextrose 5% were frozen for 3 months at −20 °C, thawed in a microwave oven with a validated cycle, and stored at 4 °C. The concentration of ketorolac was measured by HPLC. Visual inspection and pH measurement were also carried out. RESULTS: No color change or precipitation was observed. Ketorolac was stable for at least 60 days under refrigeration after freeze–thaw. Throughout this period, the lower confidence limit of the estimated regression line of the concentration–time profile remained >90% of the initial concentration, and the pH value decreased slightly without affecting chromatographic parameters. CONCLUSIONS: Within these limits, ketorolac tromethamine in dextrose 5% infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.