Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody
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Polysorbate 80 is widely used in protein formulations to protect protein against agitation-induced aggregation. In this study, we address concerns about residual peroxide present in Polysorbate 80 on protein stability. Residual peroxide may oxidize active pharmaceutical ingredients leading to reduced stability and may ultimately lead to lower potency and efficacy. The effect of Polysorbate 80 concentration on thermal and photostability of monoclonal antibody of the IgG1 subclass (MAb1) was evaluated at Polysorbate 80 concentrations ranging from 0.00% to 1.00% (w/v). MAb1 samples at 5 mg/mL with various Polysorbate 80 concentrations were subjected to accelerated thermal stress by incubation at 25°C, 40°C, and 50°C for a period of 4 weeks and light stress per ICH guideline Q1B, option 1. Our results show that Polysorbate 80 concentration of 1.00% (w/v) adversely affected thermal and photostability of MAb1. This study demonstrates the importance of carefully choosing Polysorbate 80 concentration in protein formulations to prevent destabilizing effect of Polysorbate 80 on thermal and photostability.
Key wordsaggregation monoclonal antibody non-ionic surfactant oxidation photostability Polysorbate 80 thermal stability
The authors would like to thank Stephen Tracy for performing the Polysorbate 80 assay on photostability samples.
Conflict of Interest Declaration
The authors have no personal financial or nonfinancial conflicts of interest in the publication of results contained in this manuscript.
- 4.Mahler H-C, Huber F, Kishore RSK, Reindl J, Ruckert P, Muller R. Adsorption behavior of a surfactant and a monoclonal antibody to sterilizing-grade filters. J Pharm Sci 2010; doi: 10.1002/jps.22045
- 8.Randolph TW, Jones LS. Surfactant-protein interactions. Rational design of stable protein formulations. In: Carpenter JF, Manning MC, editors. Pharm Biotechnol, vol. 13. New York: Kluwer Academic/Plenum Publishers; 2002. p. 159–75.Google Scholar
- 11.Chou DK, Krishnamurthy R, Randolph TW, Carpenter JF, Manning MC. Effects of Tween 20 and Tween 80 on the stability of albutropin during agitation. J Pharm Sci. 2005. doi: 10.1002/jps.20365.
- 14.Horowitz PM. Kinetic control of protein folding by detergent micelle, liposomes, and chaperonins, vol. 526. Washington, DC: American Chemical Society; 1993. p. 156–63.Google Scholar
- 17.Wasylaschuk WR, Harmon PA, Wagner G, Harman AB, Templeton AC, Xu H, Reed RA. Evaluation of hydroperoxides in common pharmaceutical excipients. J Pharm Sci 2006. doi: 10.1002/jps.20726
- 27.Qi P, Volkin DB, Zhao H, Nedved ML, Hughes R, Bass R, Yi SC, Panek ME, Wang D, Dalmonte P, Bond MD. Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci. 2009;98:3117–30. doi: 10.1002/jps.21617.PubMedCrossRefGoogle Scholar