Stabilizing Polysorbate 20 and 80 Against Oxidative Degradation

Area of Science:

• Pharmaceutical Science
• Chemical Engineering
• Biotechnology

Background:

• Polysorbates are essential stabilizers in therapeutic protein formulations.
• Their inherent chemical structure makes them susceptible to degradation, compromising product stability and compliance.
• Oxidative degradation is a significant concern for polysorbate stability.

Purpose of the Study:

• To evaluate the protective effect of butylhydroxytoluene (BHT) and butylhydroxyanisole (BHA) against oxidative degradation of polysorbate 20 (PS20) and polysorbate 80 (PS80).

Main Methods:

• Polysorbate solutions with and without BHT/BHA were subjected to oxidative stress (air exposure at 40°C for 7 weeks).
• Assays included peroxide levels (ferrous oxidation-xylenol orange), fatty acid content (LC-UV/MS), pH, micelle structure (LC-fluorescence), and volatile degradants (GC-MS).

Main Results:

• Polysorbate solutions with BHT or BHA exhibited significantly lower peroxide levels and free fatty acid content.
• Antioxidant-containing solutions maintained stable pH and intact polysorbate micelle structure.
• Reduced levels of volatile degradants were observed in stabilized polysorbate solutions.

Conclusions:

• BHT and BHA effectively protect PS20 and PS80 from oxidative degradation.
• Incorporating antioxidants into bulk polysorbate may enhance stability throughout manufacturing processes.
• This stabilization is vital for ensuring the integrity of pharmaceutical products.