Corpus ID: 1432672

Polysorbates, peroxides, protein aggregation, and immuno- genicity - a growing concern.

@article{Maggio2012PolysorbatesPP,
  title={Polysorbates, peroxides, protein aggregation, and immuno- genicity - a growing concern.},
  author={E. Maggio},
  journal={Journal of Excipients and Food Chemicals},
  year={2012},
  volume={3},
  pages={1108}
}
  • E. Maggio
  • Published 2012
  • Chemistry
  • Journal of Excipients and Food Chemicals
Aggregation can have a number of deleterious effects on biotherapeutics including the loss of efficacy, the induction of unwanted immunogenicity, altered pharmacokinetics, and reduced shelf life. Aggregation is ameliorated by the inclusion of surfactants in biotherapeutics formulations, typically non-ionic polymeric ether surfactants. The most commonly used examples are Tween ® 20 (Polysorbate 20) and Tween ® 80 (Polysorbate 80). Others include Triton™ X-100, Pluronic ® F-68, Pluronic ® F-88… Expand
Alkylsaccharides: circumventing oxidative damage to biotherapeutics caused by polyoxyethylene-based surfactants.
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Polysorbates and other polyoxyethylene-based surfactants are incorporated into most biotherapeutics to prevent protein aggregation in order to minimize loss of efficacy, induction of unwantedExpand
Effect of Peroxide- Versus Alkoxyl-Induced Chemical Oxidation on the Structure, Stability, Aggregation, and Function of a Therapeutic Monoclonal Antibody.
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The results of this study show that the 3 oxidants differ in terms of their effects on the structure and function of mAb8 because of chemical modification of different sets of residues located in Fab versus Fc. Expand
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It is crucially important during the pharmaceutical development of therapeutic proteins and peptides to comprehensively characterize oxidation products and evaluate the impact of oxidation-induced structural modifications on the biological properties of the drug. Expand
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The ability of dodecylmaltoside (DDM), a nontoxic alkyl saccharide surfactant, to reduce aggregation and increase the stability of interferon beta-1b (IFN)-β-1B in solution is studied. Expand
Surface Tension and Self-association Properties of Aqueous Polysorbate 20 HP and 80 HP Solutions: Insights into Protein Stabilisation Mechanisms
Polysorbates 20 and 80 are the most used surfactants for the development of parenteral protein formulations, because of their beneficial safety and stabilisation profile. Although, showing excellentExpand
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In the manufacturing process of therapeutic monoclonal antibodies (mAbs) aggregate formation is a crucial problem. Proteins tend to aggregate due to several stress conditions during processing andExpand
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Protein aggregation may cause the loss of drug potency, alter pharmacokinetic profiles, and induce unwanted immunogenicity. Albumen contains a variety of proteins and exhibits non-reversibleExpand
Effect of Chemical Oxidation on the Higher Order Structure, Stability, Aggregation, and Biological Function of Interferon Alpha-2a: Role of Local Structural Changes Detected by 2D NMR
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References

SHOWING 1-10 OF 55 REFERENCES
Peroxide formation in polysorbate 80 and protein stability.
  • Emily Ha, Wei Wang, Y. Wang
  • Chemistry, Medicine
  • Journal of pharmaceutical sciences
  • 2002
TLDR
For the first time, it is demonstrated that peroxides can be easily generated in neat polysorbate 80 in the presence of air during incubation at elevated temperatures, suggesting that implementation of an annealing step needs to be carefully evaluated in the development of a lyophilization process for oxidation-sensitive proteins in the present form. Expand
Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways.
  • B. Kerwin
  • Chemistry, Medicine
  • Journal of pharmaceutical sciences
  • 2008
TLDR
This review focuses on the chemical structure of the polysorbates, factors influencing micelle formation and factors and excipients influencing stability and degradation of thepolyethylene and fatty acid ester linkages. Expand
The Degradation of Polysorbates 20 and 80 and its Potential Impact on the Stability of Biotherapeutics
TLDR
End-of-shelf-life shaking of protein formulations showed that the stability of various monoclonal antibodies was, however, not affected, and degradation of polysorbates did not impact the Stability of the different proteins tested in pharmaceutically relevant temperature and storage conditions. Expand
Evaluation of hydroperoxides in common pharmaceutical excipients.
TLDR
Of the four excipients with substantial HPO levels, povidone, PEG 400, and HPC contain a mixture of hydrogen peroxide and organic HPOs while PS80 contains predominantly organic HPO. Expand
Effect of surfactants on the physical stability of recombinant human growth hormone.
TLDR
Higher concentrations of surfactants actually destabilized hGH as evidenced by the decrease in the onset temperature for the denaturation endotherm, as well as the failure to stabilize hGH against thermal stress in DSC studies. Expand
Quantitation of hydroperoxides in the aqueous solutions of non-ionic surfactants using polysorbate 80 as the model surfactant.
  • S. Ding
  • Chemistry, Medicine
  • Journal of pharmaceutical and biomedical analysis
  • 1993
The application of coupled oxidation of NADPH to peroxide quantitation in non-ionic surfactant solutions is demonstrated using polysorbate 80 as the model surfactant. The linearity, precision,Expand
Stabilization of recombinant human growth hormone against emulsification-induced aggregation by Pluronic surfactants during microencapsulation.
TLDR
Improvement in the release of rhGH was observed for the microspheres co-encapsulating Pluronic F127 regardless in the presence or absence of sucrose, compared to themicrospheres containing rhGH alone. Expand
Contact allergenic activity of Tween® 80 before and after air exposure
TLDR
The results indicate that allergens are present in Tween before oxidation and that new allergens arc formed in the oxidation process, which means that allergenic compounds can be formed during storage and handling of products containing ethoxylated surfactants. Expand
Dual effects of Tween 80 on protein stability.
TLDR
It is found that the dual effects of Tween 80 on the stability of IL-2SA, such as that shaking-induced aggregation ofIL-2 mutein was significantly inhibited in the presence of this surfactant, is adversely affected in terms of both oxidation and aggregation. Expand
Influence of Formaldehyde Impurity in Polysorbate 80 and PEG‐300 on the Stability of a Parenteral Formulation of BMS‐204352: Identification and Control of the Degradation Product
TLDR
A correlation was found between the formaldehyde level and the quantity of the hydroxymethyl degradant formed upon storage at 5 and 25°C and a limit test can be set as part of a strategy to limit the formation of the degradation product. Expand
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