Predicting critical micelle concentration and micelle molecular weight of polysorbate 80 using compendial methods

Braun, Alexandra; Ilko, David; Merget, Benjamin; Gieseler, Henning; Germershaus, Oliver; Holzgrabe, Ulrike; Meinel, Lorenz

doi:10.1016/j.ejpb.2014.12.015

Cited by 36 publications

(22 citation statements)

References 28 publications

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“…The surfactant concentrations explored in this study are approximately 10 times larger than the CMC of PS80 in water (13.4 ± 0.6 mg/L to 24.7 ± 1.4 mg/L) over the entire experimental temperature range of 4 C to 37 C, where higher temperatures correspond to lower CMCs and where CMC varies by supplier. 18,21 The solubility limit of m-cresol in water is 22.7 mg/mL at 25 C, 22 well above the concentrations used in this study. In buffered solutions, the citrate buffer concentration is 5 mmol/L.…”

Section: Sample Preparationmentioning

confidence: 53%

Preservative Induced Polysorbate 80 Micelle Aggregation

Gilbert

Zhang

Qian

et al. 2021

Journal of Pharmaceutical Sciences

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Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that aggregation kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. Aggregation is a two-step process, where initial formation of small aggregates is followed by a period of monotonic power-law growth, providing evidence for the mechanism. Total aggregate mass stays constant after initial aggregate formation, and addition of a pH-regulating citrate buffer dramatically accelerates aggregation kinetics.

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Section: Sample Preparationmentioning

confidence: 53%

Preservative Induced Polysorbate 80 Micelle Aggregation

Gilbert

Zhang

Qian

et al. 2021

Journal of Pharmaceutical Sciences

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“…Polysorbate 80 micelles have a reported molecular weight of ≈ 120 kDa . Thus, the micelles are retained and are coconcentrated during ultrafiltration with a 30‐kDa‐cutoff membrane.…”

Section: Resultsmentioning

confidence: 99%

Identification of aggregates in therapeutic formulations of recombinant full‐length factor VIII products by sedimentation velocity analytical ultracentrifugation

Healey

Parker

Lollar

2018

Journal of Thrombosis and Haemostasis

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Summary Background The development of inhibitory anti-factor VIII (fVIII) antibodies is the most serious complication in the management of patients with hemophilia A. Studies have suggested that recombinant full-length fVIII is more immunogenic than plasma-derived fVIII and that among recombinant fVIII products, Kogenate is more immunogenic than Advate. Aggregates in biopharmaceutical products are considered a risk factor for the development of anti-drug antibodies. Objective To evaluate recombinant full-length fVIII products for the presence of aggregates. Methods Advate, Helixate and Kogenate were reconstituted to their therapeutic formulations and subjected to sedimentation velocity analytical ultracentrifugation (SV AUC). Additionally, Advate and Kogenate were concentrated and subjected to buffer exchange by ultrafiltration to remove viscous cosolvents for the purpose of measuring s20,w values and molecular weights. Results The major component of all three products was a population of ~7.5 S heterodimers with a weight-average molecular weight of ~230 kDa. Helixate and Kogenate contained aggregates ranging from 12 S to at least 100 S, representing approximately 20% of the protein mass. Aggregates greater than 12 S represented less than 3% of the protein mass in Advate. A ~10.5 S aggregate possibly representing as a dimer of heterodimers was identified in buffer-exchanged Advate and Kogenate. SV AUC analysis of a plasma-derived fVIII product was confounded by the presence of von Willebrand factor in molar excess over fVIII. Conclusions Aggregate formation has been identified in recombinant full-length fVIII products, which is more extensive in Helixate and Kogenate. SV AUC is an an important method to characterize fVIII products.

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“…1 Like other surfactants, polysorbate 80 also forms micelles in the concentration range of 0.0010-0.0015%. [2][3][4] Owing to its amphipathic nature, polysorbate 80 has been used as a solubilizer of hydrophobic drugs, 5 wetting agent, 6 emulsier, 7 stabilizer of proteins 8 in food, cosmetic and pharmaceutical industries. 1,9 Apart from these roles, it is a potential coating agent for nanoparticulate formulations that are specically designed to target the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%