Alprostadil Stability

Availability:

• Inj Alprostadil 500mcg/ml (1ml amp)

Stability Recommendations

• Supplied as sterile solution, to be stored in a refrigerator at 2-8 ‘C
• Dilution with NS or D5
• Undiluted Alprostadil injection may interact with the plastic sidewalls of volumetric infusion chambers causing a change in the appearance of the chamber and creating a hazy solution. Should this occur, the solution and the volumetric infusion chamber should be replaced.
• When using a volumetric infusion chamber, the appropriate amount of intravenous infusion solution should be added to the chamber first.
• The undiluted Alprostadil injection should then be added to the intravenous infusion solution, avoiding direct contact of the undiluted solution with the walls of the volumetric infusion chamber.
• Dilute to volumes appropriate for the pump delivery system available.
• Prepare fresh infusion solutions every 24 hours. Discard any solution more than 24 hours old.

Rationale for Stability

• no evidence on long term stability of solution based on pediatric infusions
• recommendations can be extrapolated from similar products and stability tests

1. Stability evaluation of a prostaglandin E1 saline solution packed in insulin syringes. International Journal of Impotence Research (2001) 13

• A PGE1 solution (20 mg=ml) prepared in a saline and ethanol mixture stored at 4_C had a stability of 15.24 weeks
• more concentrated PGE1 (20 mg=0.5 ml) in saline solution, stored at 5_C, had a higher stability compared to the stability found in the other studies of PGE1 solutions (20 mg=ml) in
• water or saline. The solution containing 20 mg PGE1 per 0.5 ml normal saline stored at 5_C, maintained a concentration of 90% of the initial PGE1 solution for up to 24 weeks.
• This solution when aseptically prepared, may be packed in ready to use, unit dose syringes, for use in an auto-injector specially designed for these syringes
• A three-drug injection mixture of alprostadil 12.5 microgram/mL, papaverine hydrochloride 4.5 mg/mL and phentolamine mesylate 0.125 mg/mL in bacteriostatic 0.9% sodium chloride injection was evaluated for stability.

2. https://www.ncbi.nlm.nih.gov/pubmed/23924676

• Alprostadil was the least stable of the drug components at room temperature and under refrigeration. About 8% alprostadil loss occurred in five days at room temperature; under refrigeration losses of about 6% and 11% occurred after 1 and 2 months, respectively
• A beyond-use date of 1 month when stored refrigerated at 4 deg C is appropriate for batches of the injection that have passed sterility testing.
• Room temperature exposure should be limited, and the vial should be returned to refrigeration as soon as possible

3. https://www.ncbi.nlm.nih.gov/pubmed/3726155

• allows one to use PGE1 in an aqueous, slightly acidic solution in a system that requires it to be kept at 37 degrees C for up to 30 days such as a biologically implantable pump

4. Physicochemical stability study of a new Trimix formulation for treatment of erectile dysfunction. sep 2013. Annales Pharmaceutiques Francaise

• Prostaglandin E1 degradation rate in function of time. Degradation kinetic follows a first order equation. Based on this, the threshold of 5% degradation is reached after 33 days.