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 degrees C, thawed in a microwave oven with a validated cycle, and stored at 4 degrees 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.