Stabilizing Polysorbate 20 and 80 Against Oxidative Degradation
Purpose: Polysorbate (PS) 20 and PS80 are used in biopharmaceutical formulations to stabilize therapeutic proteins against interfacial stress. Both surfactants containing ester and ether linkages are prone to hydrolytic and oxidative degradation . The general structure of PS is displayed in Fig. 1A. The purpose of this study was to investigate if oxidative degradation of the surfactants in aqueous solution can be prevented by the addition of the antioxidants butylated hydroxyl toluene (BHT) and butylated hydroxyl anisole (BHA). The chemical structure of the antioxidants is shown in Fig. 1B and C respectively. Methods: Aqueous PS20 and PS80 samples containing either BHT, BHA or no stabilizer were incubated at 40°C, 75% RH and air exposure for seven weeks. The following analyses were performed: HPLC fluorescence micelle assay (FMA) to determine the concentration of PS, ferrous oxidation-xylenol orange (FOX) assay to quantify peroxide level, pH measurement, HS-GC-MS to characterize volatile degradants and LC-UV-MS to determine formation of free fatty acids (FFAs). Results: Samples containing an antioxidant were better stabilized in both aqueous PS20 and PS80 solutions compared to non-stabilized samples, as seen by higher micelle concentration, lower peroxide levels, stable pH, and lower degree of volatile degradants and FFAs. Conclusion: The aqueous PS20 and PS80 solutions containing BHT and BHA are more stable, i.e. less susceptible to oxidative degradation, compared to non-stabilized samples.
References:  Kishore, R. S. K. et al.: J. Pharm. Sci. 2011, 100(2):721-731