Coriolis has built up strong expertise and analytical capabilities for surfactant characterization, in particular quantification and characterization of polysorbate and polysorbate degradation products.
Surfactants stabilize biomolecules against interfacial stress and/or are prevent adsorption. Polysorbate 20 and 80 (also known as Tween) and poloxamer 188 (e.g. pluronic F68) are so far the only FDA-approved surfactants for parenteral application.
For polysorbate the structural heterogeneity, presence of degradants and other impurities makes the analytical characterization challenging. The quality requirements for pharmaceutical grade polysorbate 20 and 80 are specified in the different pharmacopoeias. The ICH countries agree on the key requirements, such as impurity levels and fatty acid composition and multicompendial polysorbates complying all current pharmacopoeias are available. For polysorbate 80, the Chinese Pharmacopoeia describes the strictest regulations for the fatty acid composition and requests an all-oleate polysorbate (≥ 98%), whereas the European and US pharmacopoeias specify a purity of ≥ 58% for oleic acid.
It is common knowledge that polysorbates are prone to undergo degradation by (i) hydrolysis and (ii) oxidation, which increases the complexity of characterization. Hydrolysis of a biopharmaceutical drug products is mainly induced by residual host cell proteins and can result in the formation of insoluble fatty acid-related particles over time.
Due to the lack of chromophores, it is required to either derivatize polysorbate with dyes or use universal detectors such as charged aerosol detectors (CAD), evaporative light scattering detectors (ELSD) or mass spectrometry (MS) in combination with liquid chromatography (LC). For the LC-based methods, it is required to develop sample preparation procedures for protein removal (e.g. organic solvent precipitation) or to isolate polysorbate (e.g. solid phase extraction (SPE))
Various analytical methods are available and required, depending on the scope of the analysis:
- Polysorbate quantification: mixed-mode online SPE or LC-CAD, fluorescence micelle assays
- Polysorbate profiling: LC-CAD or LC-MS
- Polysorbate degradation analysis for free fatty acid, oxidation products, POE ester degradation, etc.: LC-MS
- Peroxide assays: Amplex Red, Fox Assay
- Particle characterization methods
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Martos A, Koch W, Jiskoot W, Wuchner K, Winter G, Friess W, Hawe A 2017. Trends on Analytical Characterization of Polysorbates and Their Degradation Products in Biopharmaceutical Formulations. Journal of pharmaceutical sciences 106 :1722-1735.