Abstract
Polysorbates (PS) are the most common non-ionic surfactants used in protein formulations. Their degradation has been studied intensively in recent years. Ester bond hydrolysis is one of many pathways of PS degradation that can lead to accumulation of free fatty acids (FFAs) and particle formation. The distribution and quantity of FFAs in PSs impacts directly on product quality. Characterization of input PS is highly relevant, because the initial content of FFAs differs greatly between manufacturers. The purpose of this study was to set up a quick and simple analytical method for the quantitative evaluation of FFAs in PS. The content of FFAs was measured for selected PS 20 and 80, using two methods, 1H nuclear magnetic resonance spectroscopy (1H NMR) and the European pharmacopoeia method for determining acid value (IA). These methods have been evaluated using the method of standard addition and, based on the results, they are interchangeable. It was concluded that 1H NMR is a useful tool for quality control of input PS and a rapid method for indicating the rate of PS degradation by hydrolysis and oxidation. Further, a newly discovered impurity in PS raw material, the long chain ketone 12-tricosanone, can be identified using 1H NMR.
Highlights
One of the aspects that are important during the development of a biopharmaceutical is its physical and chemical stability
The content of free fatty acids (FFAs) is an important indicator of PS degradation, especially ester hydrolysis, and a useful parameter from the standpoint of PS stability testing
Accumulated FFAs, which are insoluble in water, could precipitate to form visible particles
Summary
One of the aspects that are important during the development of a biopharmaceutical is its physical and chemical stability. The most common way to stabilize protein formulations is by the use of surfactants.[1,2,3] PS are the most widely used non-ionic surfactants, but they are prone to degradation by hydrolysis and/or oxidation pathways. One of the quality evaluation parameters that is an important indicator of PS degradation, is FFA content.[4,5,6,7] Acid formation can be measured by varying the pH of the solution or by determining the total content of FFAs. Among the methods prescribed by the pharmacopoeia acid value (IA) is the only method that can detect higher FFAs content
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