Stability of tacrolimus solutions in polyolefin containers

Area of Science:

• Pharmaceutical Science
• Drug Stability Studies

Background:

• Tacrolimus is a critical immunosuppressant drug.
• Understanding its stability in various storage conditions is essential for clinical use.
• Polyolefin containers are commonly used for intravenous drug administration.

Purpose of the Study:

• To evaluate the stability of tacrolimus solutions in polyolefin containers.
• To determine the impact of temperature variations on tacrolimus solution stability.
• To establish optimal storage conditions for tacrolimus formulations.

Main Methods:

• Tacrolimus solutions at concentrations of 0.001, 0.01, and 0.1 mg/mL were prepared in 0.9% sodium chloride or 5% dextrose injection.
• Solutions were stored in polyolefin containers under room temperature (20-25 °C) and refrigerated (2-8 °C) conditions, followed by room temperature exposure.
• Stability was assessed using a stability-indicating high-performance liquid chromatography (HPLC) assay over 48 hours, with pH measurement and visual inspection.

Main Results:

• All tacrolimus solutions generally maintained over 90% of their initial concentration for up to 48 hours.
• A 0.001 mg/mL solution in 0.9% sodium chloride injection showed instability beyond 24 hours at room temperature.
• No significant changes in pH or particle formation were observed in any tested solutions.

Conclusions:

• Tacrolimus 0.001 mg/mL in 0.9% sodium chloride injection is stable for 24 hours at room temperature.
• Tacrolimus solutions (0.001 mg/mL in 5% dextrose, and 0.01-0.1 mg/mL in either diluent) are stable for at least 48 hours in polyolefin bags.
• The 0.01 mg/mL tacrolimus solution demonstrated stability under sequential temperature changes.