Effect of freezing, long-term storage and microwave thawing on the stability of a mixture of diclofenac and sodium bicarbonate in glucose 5% polyolefin bags.

Objective: Preparation in advance of intravenous solution could be efficient to improve quality assurance, security, time management and cost saving of drug delivery. The aim of this study was to investigate the stability of a mixture of diclofenac 75 mg/100 ml and sodium bicarbonate 42 mg/100 ml in 5% glucose polyolefin bags after freezing, long-term storage, and microwave thawing.

Method: The stability of five polyolefin bags containing approximately 75 mg/100ml of diclofenac and 42 mg/100ml of sodium bicarbonate in 5% glucose prepared under aseptic conditions was studied after freezing for 2 months at -20 degrees C, thawing in a microwave oven with a validated cycle, and stored at 5 + or - 3 degrees C. Diclofenac concentrations were measured by high-pressure liquid chromatography using a reversed-phase column, a mobile phase consisting of 40% of acetonitrile (v/v) in KH(2)PO(4) buffer 0.02 M, pH 8.40 + or - 0.05, and UV detection at 276.0 nm. Visual inspection, microscope observation, spectrophotometric measurements and pH measurement were also performed.

Results: No colour change or precipitation occurred in the preparations. No microaggregate was observed with optical microscopy or revealed by a change of absorbance. Based on a shelf-life of 90% residual potency, diclofenac was stable for at least 30 days after freezing and microwave thawing, period where 95% 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 not been altered.

Conclusion: Within these limits, diclofenac in 5% glucose infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.