A Mechanistic Understanding of Polysorbate 80 Oxidation in Histidine and Citrate Buffer Systems-Part 2

Doyle, Laura M.; Sharma, Anant Navanithan; Gopalrathnam, Ganapathy; Huang, Lihua; Bradley, Scott A.

doi:10.5731/pdajpst.2018.009639

Cited by 6 publications

(32 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many causes of PS oxidation have been discussed, such as heat, light, metal contaminations, or reactive oxygen species (ROS) [ 8 , 9 , 24 ]. In particular, the exposure to stainless steel or contact with metal ions from raw products have repeatedly been reported to promote PS oxidation [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. ROS such as hydroxyl radicals (HO • ), superoxide radicals ( • O 2 − ), peroxyl/hydroperoxyl radicals (ROO • /HOO • ), water peroxide H 2 O 2 , hydroperoxide (ROOH), or singlet oxygen ( 1 O 2 ) are highly reactive species, commonly found in oxidative processes.…”

Section: Introductionmentioning

confidence: 99%

Comparative Stability Study of Polysorbate 20 and Polysorbate 80 Related to Oxidative Degradation

Kozuch,

Weber,

Buske

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

The surfactants polysorbate 20 (PS20) and polysorbate 80 (PS80) are utilized to stabilize protein drugs. However, concerns have been raised regarding the degradation of PSs in biologics and the potential impact on product quality. Oxidation has been identified as a prevalent degradation mechanism under pharmaceutically relevant conditions. So far, a systematic stability comparison of both PSs under pharmaceutically relevant conditions has not been conducted and little is known about the dependence of oxidation on PS concentration. Here, we conducted a comparative stability study to investigate (i) the different oxidative degradation propensities between PS20 and PS80 and (ii) the impact of PS concentration on oxidative degradation. PS20 and PS80 in concentrations ranging from 0.1 mg⋅mL−1 to raw material were stored at 5, 25, and 40 °C for 48 weeks in acetate buffer pH 5.5 and water, respectively. We observed a temperature-dependent oxidative degradation of the PSs with strong (40 °C), moderate (25 °C), and weak/no degradation (5 °C). Especially at elevated temperatures such as 40 °C, fast oxidative PS degradation processes were detected. In this case study, a stronger degradation and earlier onset of oxidation was observed for PS80 in comparison to PS20, detected via the fluorescence micelle assay. Additionally, degradation was found to be strongly dependent on PS concentration, with significantly less oxidative processes at higher PS concentrations. Iron impurities, oxygen in the vial headspaces, and the pH values of the formulations were identified as the main contributing factors to accelerate PS oxidation.

show abstract

Section: Introductionmentioning

confidence: 99%

Comparative Stability Study of Polysorbate 20 and Polysorbate 80 Related to Oxidative Degradation

Kozuch,

Weber,

Buske

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Lam et al (2011) used EPR to detect radicals, focusing on their effect on protein oxidation rather than polysorbate degradation ( Lam et al, 2011 ). The authors of the second study, Doyle et al (2019), declared their results as “inconclusive” ( Doyle et al, 2019 ). Polysorbate degradation products were observed in the course of this study by complementary methods, but strangely no radicals were detected using EPR or nuclear magnetic resonance spectroscopy ( Doyle et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of radicals in polysorbate 80 using electron paramagnetic resonance (EPR) spectroscopy and spin trapping

Mittag¹,

Trutschel²,

Kruschwitz³

et al. 2022

International Journal of Pharmaceutics: X

View full text Add to dashboard Cite

“…The PEO radicals are the sources of significant degradation to PS molecules as they can undergo beta-scission, breaking apart the molecule releasing PEO chains, free fatty acids [ 10 , 11 , 15 , 43 ]. Additional hydroxyl radicals in the storage solutions of PS can be produced from various sources, as identified in literature, such as oxygen, UV light and metals [ 12 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…The variability in PS products is important to control since the PS is known to degrade due to both hydrolysis and oxidation, as demonstrated several times in the literature [ 7 , 8 , 9 , 10 , 11 ]. The degradation has been reported to be influenced by several factors including the storage solution, exposure to heat or light, presence of metals, exposure to oxygen and the chemical makeup of the PS itself [ 12 , 13 , 14 , 15 ]. Due to the plethora of factors influencing the potential degradation of PSs and thus affecting the commercial products in which they are used, there has been great interest from academia and industry to better understand the mechanism of degradation of PSs to better prevent the degradation from occurring.…”

Section: Introductionmentioning

confidence: 99%

“…While the hydrolysis degradation mechanism of PS is not complex, the oxidative degradation mechanism has been proposed in multiple variations [ 7 , 8 , 10 , 11 , 17 , 19 , 20 ]. All of the proposed mechanisms for oxidative degradation involve a radical mechanism even though the detection of these radical intermediates has either been unsuccessfully attempted [ 12 ] or there has been a lack of detection of the individual radical species [ 21 ]. Typically, mass spectrometry (MS) [ 8 , 11 , 22 ] or modeling predictions [ 20 ] have been used to identify non-radical intermediates and final oxidative products to propose a potential mechanism.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determining the Oxidation Mechanism through Radical Intermediates in Polysorbates 80 and 20 by Electron Paramagnetic Resonance Spectroscopy

Sutton,

Rustandi

2024

Pharmaceuticals

View full text Add to dashboard Cite

Polysorbates 20 and 80 (PS20 and PS80) are added to many commercial biologic and vaccine pharmaceuticals. It is commonly known that these polysorbates undergo a radical oxidation mechanism; however, the identity of these radical intermediates has not been clearly determined. Furthermore, PS20 and PS80 differ by the presence of a lauric acid instead of an oleic acid, respectively. The oxidation of PS80 is thought to be centered around the double bond of the oleic acid even though PS20 also undergoes oxidation, making the mechanism of oxidation unclear for PS20. Using commercial stocks of PS20 and PS80 alkyl (R•), alkoxyl (C-O•) and peroxyl (C-OO•) radicals were detected by electron paramagnetic resonance spectroscopy likely originating from radical-initiating species already present in the material. When dissolved in water, the peroxyl radicals (C-OO•) originally in the stocks were not detected but poly(ethylene oxide) radicals were. An oxidative pathway for polysorbates was suggested based on the radical species identified in the polysorbate stock material and solutions.

show abstract

A Mechanistic Understanding of Polysorbate 80 Oxidation in Histidine and Citrate Buffer Systems-Part 2

Cited by 6 publications

References 19 publications

Comparative Stability Study of Polysorbate 20 and Polysorbate 80 Related to Oxidative Degradation

Comparative Stability Study of Polysorbate 20 and Polysorbate 80 Related to Oxidative Degradation

Characterization of radicals in polysorbate 80 using electron paramagnetic resonance (EPR) spectroscopy and spin trapping

Determining the Oxidation Mechanism through Radical Intermediates in Polysorbates 80 and 20 by Electron Paramagnetic Resonance Spectroscopy

Contact Info

Product

Resources

About