Polysorbate 20

[Alexandrin Chaples]

Polysorbate80 is derived from polyethoxylated sorbitan and oleic acid. The hydrophilic groups in this compound are polyethers also known as polyoxyethylene groups, which are polymers of ethylene oxide. In the nomenclature of polysorbates, the numeric designation following polysorbate refers to the lipophilic group, in this case, the oleic acid (see polysorbate for more detail).

Polysorbate 80 is used as an emulsifier in foods, though research[6] suggests it may "profoundly impact intestinal microbiota in a manner that promotes gut inflammation and associated disease states."

For example, in ice cream, polysorbate is added up to 0.5% (v/v) concentration to make the ice cream smoother and easier to handle, as well as increasing its resistance to melting.[7] Adding this substance prevents milk proteins from completely coating the fat droplets. This allows them to join in chains and nets, which hold air in the mixture, and provide a firmer texture that holds its shape as the ice cream melts.

Polysorbate 80 is also used as a surfactant in soaps and cosmetics (including eyedrops), or a solubilizer, such as in a mouthwash. The cosmetic grade of polysorbate 80 may have more impurities than the food grade.[8]

Polysorbate 80 is also an excipient that is used to stabilize aqueous formulations of medications for parenteral administration, and used as an emulsifier in the making of the antiarrhythmic amiodarone.[9] It is also used as an excipient in some European and Canadian influenza vaccines.[10] Influenza vaccines contain 2.5 μg of polysorbate 80 per dose.[10] Polysorbate 80 is found in many vaccines used in the United States,[11] including the Janssen COVID-19 vaccine.[12] It is used in the culture of Mycobacterium tuberculosis in Middlebrook 7H9 broth. It is also used as an emulsifier in the estrogen-regulating drug Estrasorb.[13]

Some mycobacteria contain a type of lipase (enzyme that breaks up lipid molecules); when these species are added to a mixture of polysorbate 80 and phenol red, they cause the solution to change color, so this is used as a test to identify the phenotype of a strain or isolate.[15]

Polysorbates are a class of emulsifiers used in some pharmaceuticals and food preparation. They are commonly used in oral and topical pharmaceutical dosage forms. They are also often used in cosmetics to solubilize essential oils into water-based products. Polysorbates are oily liquids derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids. Common brand names for polysorbates include Kolliphor,[1] Scattics, Alkest, Canarcel, Tween,[2] and Kotilen.

The food additive polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), which is a mixture of polyoxyethylene ethers of mixed partial oleic acid esters of sorbitol anhydrides and related compounds, may be safely used in food in accordance with the following prescribed conditions:

(a) The food additive is manufactured by reacting oleic acid (usually containing associated fatty acids) with sorbitol to yield a product with a maximum acid number of 7.5 and a maximum water content of 0.5 percent, which is then reacted with ethylene oxide.

(1) An emulsifier in ice cream, frozen custard, ice milk, fruit sherbet, and nonstandardized frozen desserts, when used alone or in combination with polysorbate 65 whereby the maximum amount of the additives, alone or in combination, does not exceed 0.1 percent of the finished frozen dessert.

(2) In yeast-defoamer formulations whereby the maximum amount of the additive does not exceed 4 percent of the finished yeast defoamer and the maximum amount of the additive in the yeast from such use does not exceed 4 parts per million.

(i) Vitamin-mineral preparations containing calcium caseinate in the absence of fat-soluble vitamins, whereby the maximum intake of polysorbate 80 shall not exceed 175 milligrams from the recommended daily dose of the preparations.

(ii) Fat-soluble vitamins in vitamin and vitamin-mineral preparations containing no calcium caseinate, whereby the maximum intake of polysorbate 80 shall not exceed 300 milligrams from the recommended daily dose of the preparations.

(iii) In vitamin-mineral preparations containing both calcium caseinate and fat-soluble vitamins, whereby the maximum intake of polysorbate 80 shall not exceed 475 milligrams from the recommended daily dose of the preparations.

(8) As an emulsifier, alone or in combination with polysorbate 60, in shortenings and edible oils intended for use in foods as follows, when standards of identity established under section 401 of the act do not preclude such use:

(ii) It is used with polysorbate 60 in any combination providing no more than 1 percent of polysorbate 80 and no more than 1 percent of polysorbate 60, provided that the total combination does not exceed 1 percent of the finished shortening or oil.

(12) As an adjuvant added to herbicide use and plant-growth regulator use dilutions by a grower or applicator prior to application of such dilutions to the growing crop. Residues resulting from such use are exempt from the requirement of a tolerance. When so used or intended for use, the additive shall be exempt from the requirements of paragraph (d)(1) of this section.

(13) As a defoaming agent in the preparation of the creaming mixture for cottage cheese as identified in 133.128 of this chapter, whereby the amount of the additive does not exceed .008 percent by weight of the finished product.

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Polysorbate 60 is short for polyoxyethylene-(20)- sorbitan monostearate. It and its close relatives, polysorbate 65 and 80, work the same way as mono- and diglycerides, but smaller amounts are needed. They keep baked goods from going stale, keep dill oil dissolved in bottled dill pickles, help coffee whiteners dissolve in coffee, and prevent oil from separating out of artificial whipped cream. A 2015 study of polysorbate 80 and another emulsifier (carboxymethylcellulose) in mice found that both affected gut bacteria and triggered inflammation and other changes in the gut, as well as obesity and metabolic syndrome. In mice that were predisposed to colitis, the emulsifiers promoted the disease. It is possible that polysorbates and other emulsifiers act like detergents to disrupt the mucous layer that lines the gut, and that the results of this study may apply to other emulsifiers as well. Research needs to be done to determine long-term effects of these and other emulsifiers at levels that people consume.

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Polysorbate 80 and polysorbate 20 are the most commonly used surfactants in formulations to stabilize therapeutic proteins against interfacial stresses. Polysorbates can undergo oxidative or enzyme-mediated hydrolytic degradation to produce subvisible particles in formulations. The impact of fatty acid composition on the stability of polysorbate in formulation and subsequently on protein product quality has not been clearly understood. In the present study we compared the hydrolysis of compendial and super refine grade polysorbate 20 using two enzymes for the (i) release free fatty acid, (ii) formation of subvisible particles, and (iii) impact of polysorbate 20 degradation on protein quality.

Three therapeutic protein formulations with or without 1mg/mL therapeutic protein were prepared using matching formulation buffers containing compendial or super refine grade of polysorbate 20 with pH ranging from 4.0 to 6.2. Formulations were spiked with either esterase or lipase enzymes, and the release of free fatty acids in formulation buffers and formation of particles were monitored after incubation at 4C or 37C. Protein quality was monitored via changes in secondary structures, formation of high molecular weight species, and biological activity.

Our results indicate that addition of hydrolytic enzymes increase free fatty acid concentration and number of subvisible particles in formulation buffer at 4C or 37C for both grades of polysorbate 20. The free fatty acid concentration remains stable at 4C over a month but decreases after 2 hours of incubation at 37C. Release of free fatty acid and formation of sub-visible particles were found to be temperature- and pH-dependent with relatively greater number of particles at acidic pH compared to near neutral pH. Degradation of polysorbate 20 and formation of sub-visible particles did not show significant impact on biological activity of protein or stability against degradation or aggregation to form high molecular weight species. Overall, our results indicate that hydrolysis of polysorbate is one of the sources for the formation of subvisible particles in therapeutic protein formulation, but additional studies are required to better understand the safety and quality impact of particles originated from free fatty acids.

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