An API is formulated with PEG 3350, Polysorbate 80, NaCl, Methyl paraben. While heating small batch in water bath at 120 C , no color change was observed, but while heating in an autoclave of large scale, a small amount of yellow colored substance was observed at the top of the API. What causes this color formation?
Hi, Polysorbate 80 on degradation undergoes oxidation and shows yellow colour formation.
Both PEG3350 and Polysorbate 80 produce a yellow colourartion when oxidised. The oxidation can be due to peroxides generated when the excipients undergo thermal degradation.
Hello,
To what temperature can we heat PS80 solution without having to worry about the degradation and for how long?
Polysorbate 80 is undergoes degradation over time both in bulk as well as in aqueous solutions by two mechanisms a) auto-oxidation, cleavage at the ethylene oxide subunits; b) hydrolysis of the fatty acid ester bond.
Polyoxyethylene chains are susceptible, in presence of oxygen over time, to oxidation of C-H groups to C-O-O-H (hydroperoxy) groups. The generation of peroxides and hydroperoxides from the auto-oxidative degradation of the polysorbate surfactants appears to result from reactive radical formation at both the polyoxyethylene and the olefin sites within the molecules. The hydroperoxy groups are susceptible to further degradation which leading to cleavage of the polyoxyethylene chains and, at least in a particular situations, formation of carbonyl compounds such as formaldehyde and acetaldehyde which is further degraded to formic acid and/or other compounds as degradation products with a concomitant lowering of pH. Increased degradation leads to larger amounts of low molecular weight acids and, thus, a lower pH.
Oxidative degradation can also affect formulation ingredients other than those comprising polyoxyethylene chains, with a variety of undesirable effects, including, in addition to decline in physical stability and pH drift, Accumulation of degradation products that can be toxic or otherwise deleterious if administered by injection, and, where the ingredient subject to oxidative degradation is an active ingredient, loss of potency.
In aqueous formulations polysorbates can also hydrolyze with an apparent half-life of five months at 40°C. So due to hydrolysis of polysorbate 80, resulting degraded product may causes yellow coloration.
Higher Temperature may accelerated auto-oxidation and hydrolysis of polysorbate 80 and thus incease in degradation products.
Studies of polysorbate 80 at 80 oC showed that the reaction was catalyzed markedly below pH 3 and above pH 7.6. The lowest rates were obtained between pH 3–7.6 being essentially constant within that range.
Light also increases the rate of polysorbate degradation in solution.
The resulting degradation product may be responsible for yellow coloration of final solution after heating at 120 C.
Storing the polysorbate solutions away from light, in the presence of nitrogen, pH between 3-7.6 most probably 5-7 and at lower temperatures helps prevent degradation from occurring and color change.
Yes it does and the cause is very well explained above espacially by Dhruv Butani with references. Regards
Thanks Mr. Dhurv Bhutani. It was very helpful. In addition, I wondering about the micelle forming abilities of polysorbate 80. What could impact the stability of micelles of Polysorbate 80?
In addition, when polysorbate 80 is hydrolyzed in acidic solution, the fatty acid (hydrophobic part of polysorbate 80) is produced. When the content of fatty acid is over its solubility, visible aggregates appears in the solution.
Can anyone tell how tween 80 smells and taste when fresh? And when degraded how it smells. How to remove its odour and bitter taste during liquid formulation?
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