Degradation of Polysorbates 20 and 80: Studies on Thermal Autoxidation and Hydrolysis

Kishore, Ravuri S. K.; Pappenberger, Astrid; Dauphin, Isabelle Bauer; Ross, Alfred; Buergi, Beatrice; Staempfli, Andreas; Mahler, Hanns‐Christian

doi:10.1002/jps.22290

Cited by 243 publications

(176 citation statements)

References 46 publications

(70 reference statements)

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“…Higher temperature can lead to degradation of Polysorbate 80 and increase the peroxide content, as demonstrated by Ha et al who reported that after incubation of Polysorbate solution at 40°C for 5 weeks, there was an eightfold increase in peroxide content when compared with solution stored under dark conditions (5). Kishore et al have also reported polysorbates undergoing degradation through autooxidation and hydrolysis at higher temperatures (29). The presence of transition metals such as copper may also catalyze auto-oxidation of polysorbates (6).…”

Section: Discussionmentioning

confidence: 99%

Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody

et al. 2012

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Abstract. Polysorbate 80 is widely used in protein formulations to protect protein against agitationinduced 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.

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Section: Discussionmentioning

confidence: 99%

Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody

et al. 2012

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“…Polysorbates are well known to be vulnerable to degradation. Autoxidation of ethylene oxide units is the dominant degradation process that occurs below 40°C, while hydrolysis of ester bonds becomes more important above this temperature (e.g., Kishore et al, 2011b, and references therein). Autoxidation produces peroxides, aldehydes, acids, ketones, n-alkanes, and fatty acid esters via radical initiation, propagation, and termination reactions (Kerwin, 2008;Kishore et al, 2011b).…”

Section: Surfactants For Extraterrestrial Organic Extractionmentioning

confidence: 99%

“…Autoxidation of ethylene oxide units is the dominant degradation process that occurs below 40°C, while hydrolysis of ester bonds becomes more important above this temperature (e.g., Kishore et al, 2011b, and references therein). Autoxidation produces peroxides, aldehydes, acids, ketones, n-alkanes, and fatty acid esters via radical initiation, propagation, and termination reactions (Kerwin, 2008;Kishore et al, 2011b). Autoxidation can be slowed by measures that prevent radical initiation, such as excluding peroxides, heat, light, and oxygen (Yao et al, 2009;Kishore et al, 2011a), or the addition of an antioxidant such as butylated hydroxytoluene (Donbrow, 1987), while removing transition metal ions such as copper can also reduce catalytic effects (Kerwin, 2008).…”

Section: Surfactants For Extraterrestrial Organic Extractionmentioning

confidence: 99%

“…Organic acids produced by the autoxidation of ethylene oxide units (Kerwin, 2008;Kishore et al, 2011b) should increase acidity and electrical conductivity, although the effects on pH may be obscured by chemistry related to the degradation of the fluorocarbon and polysiloxane chains, in the cases of Zonyl FS-300 and PDMSHEPMS. Mitigation of the degradation of surfactants may be possible.…”

Section: Surfactants For Extraterrestrial Organic Extractionmentioning

confidence: 99%

“…The ability of the solutions stored at low temperatures to extract the spiked standards at reasonable efficiencies, similar to those obtained by using fresh solutions, indicates that oxidation related to oxygen dissolved in the solvent and present in the headspace is not a significant problem. Autoxidation of ethylene oxide units is the dominant degradation pathway affecting polysorbates below 40°C (e.g., Kishore et al, 2011b, and references therein). The ability of antioxidants to protect against autoxidation (Donbrow, 1987) suggests that ascorbic acid may be responsible for observed improvements in extraction efficiency.…”

Section: Surfactant Solution Compositionmentioning

confidence: 99%

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Searching for Life on Mars: Degradation of Surfactant Solutions Used in Organic Extraction Experiments

et al. 2014

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Life-detection instruments on future Mars missions may use surfactant solutions to extract organic matter from samples of martian rocks. The thermal and radiation environments of space and Mars are capable of degrading these solutions, thereby reducing their ability to dissolve organic species. Successful extraction and detection of biosignatures on Mars requires an understanding of how degradation in extraterrestrial environments can affect surfactant performance. We exposed solutions of the surfactants polysorbate 80 (PS80), Zonyl FS-300, and poly[dimethylsiloxane-co-[3-(2-(2-hydroxyethoxy)ethoxy)propyl]methylsiloxane] (PDMSHEPMS) to elevated radiation and heat levels, combined with prolonged storage. Degradation was investigated by measuring changes in pH and electrical conductivity and by using the degraded solutions to extract a suite of organic compounds spiked onto grains of the martian soil simulant JSC Mars-1. Results indicate that the proton fluences expected during a mission to Mars do not cause significant degradation of surfactant compounds. Solutions of PS80 or PDMSHEPMS stored at -20°C are able to extract the spiked standards with acceptable recovery efficiencies. Extraction efficiencies for spiked standards decrease progressively with increasing temperature, and prolonged storage at 60°C renders the surfactant solutions ineffective. Neither the presence of ascorbic acid nor the choice of solvent unequivocally alters the efficiency of extraction of the spiked standards. Since degradation of polysorbates has the potential to produce organic compounds that could be mistaken for indigenous martian organic matter, the polysiloxane PDMSHEPMS may be a superior choice of surfactant for the exploration of Mars.

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Late‐Stage Product Characterization: Applications in Formulation, Process, and Manufacturing Development

Chan¹,

Shi

2014

Biophysical Methods for Biotherapeutics

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Degradation of Polysorbates 20 and 80: Studies on Thermal Autoxidation and Hydrolysis

Cited by 243 publications

References 46 publications

Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody

Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody

Searching for Life on Mars: Degradation of Surfactant Solutions Used in Organic Extraction Experiments

Late‐Stage Product Characterization: Applications in Formulation, Process, and Manufacturing Development

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