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Polysorbate 80

Polysorbate 80 (also known as Tween 80) is a synthetic nonionic surfactant and emulsifier, chemically designated as polyoxyethylene (20) sorbitan monooleate, prepared from the esterification of sorbitol with oleic acid followed by ethoxylation with approximately 20 moles of ethylene oxide.^[1] With a molecular formula of C₆₄H₁₂₄O₂₆ and an average molecular weight of about 1310 Da, it appears as a viscous, amber-colored, water-soluble liquid that functions by lowering surface tension to facilitate the mixing of immiscible substances like oils and water.^[2] Widely applied across industries, Polysorbate 80 serves as an emulsifier and stabilizer in food products such as ice cream, salad dressings, and baked goods to prevent separation and enhance texture, with usage limited according to specific applications (e.g., up to 0.1% in frozen desserts).^[1] In cosmetics and personal care items, it acts as a solubilizer for fragrances and essential oils, improving product clarity and spreadability. In pharmaceuticals and vaccines, it stabilizes aqueous formulations of drugs and biologics, preventing protein adsorption to surfaces and aggregation, as seen in injectable therapies and certain influenza vaccines.^[2]^[3] The U.S. Food and Drug Administration classifies Polysorbate 80 as generally recognized as safe (GRAS) for its approved food uses, based on extensive toxicological data showing low acute toxicity and no carcinogenic effects in animal studies at relevant doses.^[4]^[5] However, it can cause rare hypersensitivity reactions, particularly in patients with a history of allergies to polyethylene glycol derivatives, and its degradation products like peroxides may affect formulation stability in biotherapeutics.^[6] Regulatory bodies such as the European Food Safety Authority also affirm its safety for use as a feed additive and in human foods when within specified limits.^[7]

Chemistry

Molecular Structure

Polysorbate 80, chemically known as polyoxyethylene (20) sorbitan monooleate, is a nonionic surfactant synthesized by first dehydrating sorbitol to form sorbitan, followed by esterification of the sorbitan with oleic acid at one hydroxyl group, and subsequent ethoxylation of the remaining hydroxyl groups with an average of 20 ethylene oxide units. This structure features a sorbitol-derived backbone that provides a cyclic ether ring with multiple attachment points, enabling the incorporation of both hydrophobic and hydrophilic moieties essential for its surfactant properties. The approximate molecular formula of Polysorbate 80 is C₆₄H₁₂₄O₂₆, with a molecular weight around 1,310 g/mol, though this represents an average due to polydispersity arising from the variable degree of ethoxylation during synthesis, resulting in a mixture of chains with differing numbers of ethylene oxide units. In the molecular architecture, the lipophilic region is dominated by the sorbitan-oleic ester, where the unsaturated C18 oleic acid chain (with a cis double bond at position 9) provides hydrophobicity, while the hydrophilic polyoxyethylene chains—repeating -OCH₂CH₂O- units—extend from the sorbitan, conferring water solubility and enabling emulsification. This structural motif distinguishes Polysorbate 80 from other polysorbates in the family; for instance, Polysorbate 20 employs lauric acid (a saturated C12 fatty acid) for esterification, yielding a shorter and less unsaturated lipophilic tail that alters its solubility and stability profile compared to the oleic acid-based Polysorbate 80.

Physical and Chemical Properties

Polysorbate 80 appears as a viscous, water-soluble liquid ranging in color from yellow to amber. Its average molecular weight is approximately 1310 Da, reflecting its polydisperse nature due to varying degrees of ethoxylation and fatty acid chain lengths.^[8] Key physical properties include a density of 1.06–1.08 g/cm³ at 25 °C and a refractive index of 1.467–1.470. The hydrophilic-lipophilic balance (HLB) value is 15, which supports its role in oil-in-water emulsification.^[9] Polysorbate 80 exhibits high solubility in water (approximately 100 g/L), ethanol, and fixed oils such as cottonseed and corn oil, but it is insoluble in mineral oil.^[10] Chemically, Polysorbate 80 is stable under neutral to mildly acidic conditions but undergoes hydrolysis under strong acidic or basic environments, as well as enzymatic action, leading to degradation into free fatty acids and polyoxyethylene sorbitan.^[11]

Synthesis

Polysorbate 80 is industrially produced from anhydrous sorbitol, oleic acid, and ethylene oxide as the primary starting materials. The process commences with the dehydration of sorbitol to yield sorbitan, a cyclic polyol intermediate, followed by esterification of the sorbitan with oleic acid to form sorbitan monooleate. This esterification step typically occurs under acidic or thermal conditions to promote the formation of the monoester while minimizing polyesters.^[12] The key subsequent step is ethoxylation, in which approximately 20 moles of ethylene oxide are added per mole of sorbitan monooleate to introduce the polyoxyethylene chains. This reaction is catalyzed by a base, such as potassium hydroxide or potassium carbonate (typically 0.1-1% by weight), and conducted at temperatures between 120°C and 180°C under moderate pressure (1-2 bar) to ensure efficient incorporation of the ethylene oxide. The conditions control the degree of polymerization, resulting in a mixture of homologues with varying ethoxylate chain lengths.^[13]^[14]^[15] After ethoxylation, purification is essential to remove unreacted ethylene oxide, excess sorbitan esters, and low-molecular-weight impurities. Common methods include vacuum distillation or molecular distillation under reduced pressure (e.g., 0.1-10 mmHg) at elevated temperatures (150-200°C), or solvent extraction, achieving pharmaceutical-grade purity exceeding 99%. These steps ensure compliance with standards for food, cosmetic, and medicinal applications.^[16] Industrial production can employ either batch or continuous processes. In batch operations, reactants are charged into a reactor for sequential addition of ethylene oxide, while continuous systems use loop reactors for steady-state ethoxylation, improving efficiency for large-scale output. Variations in reaction parameters, such as catalyst concentration and temperature, directly impact the polydispersity index of the ethoxylate chains, influencing the product's emulsifying performance and stability. The foundational synthesis method for Polysorbate 80 was developed in the 1940s by Imperial Chemical Industries as part of the Tween series of nonionic emulsifiers, marking an early advancement in ethoxylated sorbitan esters.^[17]

Nomenclature

Chemical Designations

Polysorbate 80, a nonionic surfactant, has the systematic IUPAC name Sorbitan, mono-(9Z)-9-octadecenoate, poly(oxy-1,2-ethanediyl) derivs., which describes its structure as a derivative of sorbitan esterified with oleic acid and ethoxylated with ethylene oxide units.^[18] This nomenclature highlights the polyoxyethylene chain derived from ethylene oxide, the sorbitan core, and the specific fatty acid ester. It is also commonly designated in chemical literature as sorbitan monooleate polyoxyethylene ether, emphasizing the monoester linkage with oleic acid.^[19] The compound is assigned the Chemical Abstracts Service (CAS) registry number 9005-65-6, which uniquely identifies it in chemical databases worldwide. In the European Inventory of Existing Commercial Chemical Substances (EINECS), it is listed under the number 500-019-9, facilitating regulatory tracking across the European Union.^[8] In food additive contexts, Polysorbate 80 is designated as E 433 under the International Numbering System for Food Additives, as established by the Codex Alimentarius Commission and adopted in the European Union.^[20] The naming convention for Polysorbate 80 reflects its composition: the "80" suffix indicates the oleic acid (an 18-carbon unsaturated fatty acid) as the lipophilic component esterified to sorbitan, while the polyoxyethylene portion typically involves an average of 20 ethylene oxide units for ethoxylation, conferring hydrophilic properties.^[21] This degree of ethoxylation varies slightly in commercial preparations but averages around 20 units, influencing its surfactant characteristics.^[18]

Commercial and Common Names

Polysorbate 80 is widely recognized in commercial and industrial contexts under the primary trade name Tween 80, a registered trademark owned by Croda International Plc. This name is commonly used across food, pharmaceutical, and cosmetic formulations for its emulsifying properties. Other notable commercial names include Montanox 80, marketed by Seppic as a high-purity variant suitable for injectable and pharmaceutical applications,^[22] and Crillet 4, offered by Croda as a food-grade emulsifier derived from vegetable sources.^[23] In scientific and technical literature, polysorbate 80 is frequently referred to by synonyms such as polyoxyethylene (20) sorbitan monooleate, which describes its ethoxylated structure, and sorbitan monooleate ethoxylate, emphasizing its derivation from sorbitan and oleic acid.^[1] Abbreviations like PS80 or P80 are prevalent in pharmaceutical and biopharmaceutical documentation, where they denote its role as a surfactant and stabilizer in protein formulations.^[24] Regionally, in the European Union, it is designated as E433 for food labeling purposes under harmonized regulations.^[25]

Applications

Food Industry

Polysorbate 80 serves as a key emulsifier in the food industry, primarily functioning to stabilize oil-in-water mixtures and prevent phase separation in various processed foods. As a nonionic surfactant, it enables the uniform dispersion of fats and oils in aqueous environments, which is essential for maintaining product consistency during manufacturing, storage, and consumption.^[26] This property makes it particularly valuable in formulations where immiscible ingredients must coexist without segregating. In approved applications, Polysorbate 80 is designated as the food additive E433 in the European Union and is regulated by the U.S. Food and Drug Administration (FDA) under 21 CFR 172.840 for use in specific food categories. Typical concentrations range from 0.01% to 0.5% by weight, depending on the product; for instance, it is incorporated at up to 0.1% in ice cream to enhance fat globule stability and at similar levels in mayonnaise and baked goods to improve emulsion integrity.^[1]^[27] These levels ensure effective emulsification without altering the sensory profile significantly. The benefits include enhanced texture through smoother mouthfeel, extended shelf life through emulsion stability and prevention of oxidation, and better dispersion of flavors and fats for consistent taste distribution. Emerging research as of 2025 suggests that emulsifiers like polysorbate 80 may alter gut microbiota and intestinal health, though regulatory approvals remain in place.^[28]^[29] Specific examples highlight its versatility: in ice cream and frozen desserts, it promotes partial fat destabilization to create a creamy overrun while preventing ice crystal formation; in salad dressings and chocolate, it emulsifies oils to avoid separation and inhibit fat bloom, a surface defect caused by cocoa butter recrystallization. Additionally, Polysorbate 80 stabilizes emulsions in non-dairy creamers, allowing vegetable fats to mimic the performance of dairy-based alternatives without creaming or oiling off.^[30]^[31] Regarding regulations, the FDA deems it safe for listed uses with limits such as 500 parts per million in pickles, while the EU sets maximum levels at 500 mg/kg in certain foods like pickled products under Regulation (EC) No 1333/2008, with quantum satis permissions in others like fine bakery wares.^[1]

Cosmetics and Personal Care

Polysorbate 80 functions as a nonionic surfactant in cosmetics and personal care products, primarily serving as an emulsifier to blend oil and water phases, a solubilizer for essential oils and fragrances, and a dispersant for active ingredients. Its hydrophilic-lipophilic balance (HLB) value of 15 makes it particularly effective for creating stable oil-in-water emulsions in formulations like creams and lotions.^[32] This versatility allows it to enhance the homogeneity and sensory attributes of products, such as improving spreadability on the skin by reducing phase separation.^[33] In specific applications, Polysorbate 80 is commonly incorporated into hair conditioners at concentrations of 1-5% to disperse conditioning agents like silicones and oils evenly throughout the formula, promoting uniform application and rinse-off performance.^[34] It is also used in body washes and shampoos as a dispersant to ensure consistent distribution of cleansing and moisturizing components, typically at 0.5-10% in rinse-off products.^[32] For perfumes, it enhances fragrance solubility in aqueous bases at up to 11.9%, allowing for clearer and more stable scent delivery.^[32] These uses contribute to overall formulation stability by maintaining micelle structures that prevent ingredient clumping or settling.^[33] A notable example is its role in sunscreen emulsions, where Polysorbate 80 at around 5% helps integrate UV filters and emollients into a single phase, improving product texture and efficacy without compromising stability.^[35] The Cosmetic Ingredient Review (CIR) Expert Panel has evaluated Polysorbate 80 and concluded it is safe for cosmetic use when formulated to be nonirritating, with maximum reported concentrations reaching 18.1% in rinse-off products like shampoos and body washes.^[32] This approval supports its widespread adoption in personal care for enhancing product performance and user experience.^[36]

Pharmaceuticals

Polysorbate 80 serves as a critical excipient in pharmaceutical formulations, primarily functioning as a stabilizer to prevent protein aggregation in biologics such as vaccines and injectables, and as a solubilizer for poorly water-soluble drugs.^[37]^[38] In biologic products, it mitigates protein loss due to adsorption on surfaces and protects against interfacial denaturation during manufacturing, storage, and administration.^[37] For vaccines, including certain COVID-19 formulations like the AstraZeneca and Janssen vaccines, polysorbate 80 stabilizes emulsions and prevents aggregation of protein components, ensuring formulation integrity.^[39]^[40] Specific applications of polysorbate 80 span various dosage forms, including oral tablets, intravenous (IV) solutions, and eye drops. In oral tablets and IV solutions, it enhances the solubility of hydrophobic active pharmaceutical ingredients, enabling effective delivery.^[41] In eye drops, such as artificial tears for dry eye relief, it acts as a lubricant and solubilizer at low concentrations.^[42] Typical concentrations in biologic formulations range from 0.01% to 0.1% (w/v), sufficient to provide stabilization without excessive surfactant load.^[43]^[44] The benefits of polysorbate 80 include reducing protein aggregation by interacting with hydrophobic regions on protein surfaces and improving overall formulation stability against environmental stresses.^[24] It is notably used in preparations like amphotericin B lipid formulations to solubilize the antifungal agent and in docetaxel chemotherapy to enable IV administration of the poorly soluble taxane.^[45]^[46] Recent developments highlight its role in post-2020 viral vector COVID-19 vaccines, such as AstraZeneca and Janssen, for maintaining emulsion stability.^[39] However, degradation studies have revealed that polysorbate 80 can undergo oxidative breakdown to form peroxides, particularly in the presence of metals or light, potentially impacting long-term formulation safety.^[47]^[48] Pharmacopeial standards for polysorbate 80 are outlined in the United States Pharmacopeia (USP)/National Formulary (NF) monograph, which specifies purity requirements including limits on peroxide value (not more than 10 meq/kg), fatty acid composition, and absence of heavy metals to ensure suitability for pharmaceutical use.^[49]^[18]

Laboratory and Industrial Uses

In laboratory settings, Polysorbate 80 serves as a supplement in cell culture media to protect cells from shear stress induced by agitation or mixing, thereby preventing aggregation and maintaining viability during bioreactor processes.^[50] It is commonly added at concentrations around 0.01-0.1% to stabilize proteins and reduce interfacial damage in mammalian cell cultures.^[51] In microbiology, Polysorbate 80 facilitates bacterial dispersion by deaggregating clumped cells, enhancing detection and enumeration; for instance, 0.05% is incorporated into agar media like tryptic soy agar with lecithin to neutralize disinfectants and promote even microbial growth.^[52]^[53] Industrially, Polysorbate 80 functions as a wetting agent in textile processing, improving dye penetration and fabric finishing by reducing surface tension and aiding uniform application.^[54] In paints and inks, it promotes pigment dispersion, ensuring stable emulsions and preventing settling, which enhances color consistency and application performance in formulations like latex paints.^[55]^[56] Beyond these, Polysorbate 80 aids vaccine production as an emulsifier and stabilizer during manufacturing, helping to maintain antigen suspension and prevent phase separation in formulations.^[57] In analytical chemistry, it is employed as a mobile phase additive in high-performance liquid chromatography (HPLC), particularly in micellar liquid chromatography, to improve solubility of hydrophobic analytes and enhance separation efficiency.^[58] Its low toxicity profile enables widespread use in sensitive laboratory environments without compromising safety.^[59] Additionally, its biodegradability supports eco-friendly applications in industrial processes.^[60] Representative examples include its role in stabilizing biofuel emulsions, where it blends alcohol-gasoline mixtures to improve fuel homogeneity and combustion efficiency.^[61] In biotechnology research and development, Polysorbate 80 stabilizes enzymes against denaturation, preserving activity during storage and experimental manipulations.^[62]

Safety and Regulation

Toxicity and Health Effects

Polysorbate 80 exhibits low acute toxicity, with an oral LD50 greater than 25 g/kg in rats, indicating it is non-toxic at doses far exceeding typical human exposure levels.^[5] Inhalation and dermal routes also show minimal acute effects, with no significant irritation or sensitization observed in standard assays.^[63] Chronic exposure studies demonstrate no clear carcinogenic potential for Polysorbate 80 overall. In two-year NTP feed studies, male and female F344/N rats and B6C3F1 mice were administered up to 25,000 ppm (approximately 2.5% in diet), revealing equivocal evidence of carcinogenic activity in male F344/N rats based on increased incidences of interstitial cell adenomas of the testes; no evidence of carcinogenic activity in female rats or mice.^[64] Reproductive and developmental toxicity studies, including multi-generation rat studies, have generally shown no adverse effects at doses up to several grams per kg body weight per day. Upon ingestion, Polysorbate 80 undergoes enzymatic hydrolysis primarily by pancreatic lipase, breaking down into sorbitol, oleic acid, and polyoxyethylene (PEG) moieties.^[65] The resulting oleic acid is metabolized via beta-oxidation, sorbitol is absorbed and utilized as an energy source, and low-molecular-weight PEG fragments are excreted primarily through renal clearance without accumulation.^[66] For human exposure, Polysorbate 80 is considered safe at intakes below 25 mg/kg body weight per day, as established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) acceptable daily intake (ADI).^[20] It shows no genotoxic potential in bacterial mutagenicity assays or in vivo studies, supporting its safety in food, pharmaceutical, and cosmetic applications at regulated levels.^[66] Recent studies from the 2020s highlight oxidative degradation of Polysorbate 80 in formulations, where peroxides form as impurities or degradation products via autoxidation, particularly under exposure to light, heat, or metal ions.^[67] These peroxides can propagate further oxidation but have not been linked to significant toxicity at trace levels typical in stabilized products; however, they underscore the need for antioxidant controls in biopharmaceuticals to maintain stability.^[68] Emerging research from the 2020s, primarily in rodent models, has raised concerns about potential effects on gut health. For example, dietary exposure to polysorbate 80 has been associated with alterations in gut microbiota, increased intestinal permeability, low-grade inflammation, and accelerated cognitive decline in aging mice, possibly via bile acid metabolism changes and neuroinflammation. These findings suggest possible risks at higher chronic exposures, though human relevance remains under investigation as of 2025, with no changes to established safety thresholds.^[69]^[70]

Allergic Reactions

Allergic reactions to polysorbate 80 are rare, with documented cases of anaphylaxis limited to isolated incidents rather than widespread occurrences. For instance, cases of anaphylaxis have been reported following administration of the human papillomavirus (HPV) vaccine Gardasil, which contains polysorbate 80 as an excipient; one pre-2020 case in a young girl was confirmed due to polysorbate 80 via intradermal testing, while a polysorbate 80-free alternative was negative. Cross-reactivity with polyethylene glycol (PEG) has been observed in some patients, attributed to structural similarities between the excipients, leading to positive skin tests for both in up to 12.7% of high-risk individuals evaluated for vaccine hypersensitivity.^[71]^[72]^[73] The primary mechanism for true allergic responses is IgE-mediated hypersensitivity, often triggered by impurities in polysorbate 80 formulations, such as ethylene oxide residues from its synthesis or macromolecular contaminants that elicit immune recognition. Protein contaminants or oxidative byproducts like peroxides may also contribute to sensitization in susceptible individuals. However, many reported reactions are anaphylactoid (non-IgE-mediated), involving complement activation or mast cell degranulation independent of prior exposure.^[74]^[75]^[76] Risk factors for allergic reactions include a prior history of hypersensitivity to related nonionic surfactants or excipients like PEG, as well as administration via parenteral routes such as intravenous infusion, where systemic exposure is higher and reactions occur more frequently than with oral or topical applications. Patients with multiple drug allergies represent a higher-risk group, as evidenced by elevated rates of positive skin testing in this population.^[72]^[77] Case studies primarily involve isolated hypersensitivity events in pharmaceutical contexts, such as intravenous oncology drugs where polysorbate 80 is used as a solubilizer; for example, reactions during docetaxel infusions have been linked to the excipient, though these are often anaphylactoid rather than purely allergic. No large-scale outbreaks or epidemics of polysorbate 80 allergy have been documented across global use.^[2] Mitigation strategies focus on using hypoallergenic grades of polysorbate 80 formulated to minimize impurities, including low levels of peroxides, ethylene oxide, and other reactive species, which reduces the potential for both IgE-mediated and anaphylactoid responses in sensitive patients. Skin prick or intradermal testing prior to exposure in at-risk individuals can further guide safe administration.^[76]^[72]

Regulatory Status

Polysorbate 80 is recognized by the U.S. Food and Drug Administration (FDA) as safe for use as a direct food additive under 21 CFR 172.840, permitting its application as an emulsifier, stabilizer, and solubilizer in various food categories with specified maximum levels, such as up to 0.1% in baked goods and 0.015% in ice cream.^[1] In pharmaceuticals, it is approved as an inactive ingredient (excipient) for oral, injectable, and topical formulations, with the FDA's Inactive Ingredient Database listing concentrations up to 10 mg/mL for intravenous use and higher for oral solutions. In the European Union, Polysorbate 80 is authorized as the food additive E433 under Regulation (EC) No 1333/2008, included in Annex II for use as an emulsifier in categories like fine bakery wares (up to 3000 mg/kg) and emulsified sauces (up to 5000 mg/kg), subject to quantum satis limits where no maximum is specified. For cosmetics, it is permitted without specific restrictions under Regulation (EC) No 1223/2009, as it does not appear in Annex III (list of substances with concentration limits) or Annex II (prohibited substances), allowing its use as a surfactant and emulsifier provided overall product safety is ensured. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has established an acceptable daily intake (ADI) of 0-25 mg/kg body weight for Polysorbate 80 and related polyoxyethylene sorbitan esters, based on toxicological evaluations confirming no adverse effects at this level.^[20] It is also standardized in major pharmacopeias, including monographs in the United States Pharmacopeia (USP), British Pharmacopoeia (BP), and Indian Pharmacopoeia (IP), which specify purity criteria such as minimum 58% monooleate content, limits on peroxides (≤10 meq/kg), and heavy metals (≤10 ppm) to ensure quality for pharmaceutical applications.^[78] In Germany, the Federal Institute for Risk Assessment (BfR) aligns with EU regulations but recommends cautious use of emulsifiers in infant foods, limiting additives like Polysorbate 80 in baby formulae and follow-on products to essential levels only, in line with Directive 2006/125/EC, which permits it quantum satis but emphasizes minimal exposure for vulnerable groups. Recent updates in the 2020s for biologics include enhanced USP guidelines on Polysorbate 80 purity (revised 2016, with ongoing implementation) and FDA/EMA emphasis on monitoring degradation products like peroxides in biopharmaceutical formulations to prevent particle formation and ensure stability.^[79]^[80] There are no major global bans on Polysorbate 80, though it faces scrutiny in organic foods; as a synthetic emulsifier, it is prohibited in USDA-certified organic products under the National Organic Program (7 CFR 205.605), which allows only nonsynthetic alternatives unless explicitly listed on the National List, which it is not.

History

Development

Polysorbate 80, known commercially as Tween 80, was developed in the 1940s as part of the Tween series of nonionic surfactants designed for emulsification applications.^[81] This series emerged from efforts by Imperial Chemical Industries (ICI) to create synthetic alternatives to natural emulsifiers, addressing demands in various industries during that era.^[17] A pivotal contribution came from the Atlas Powder Company, a precursor to Croda International, which focused on sorbitan-based ethoxylates. In 1943, the company filed for a patent on the synthesis of polyoxyethylene sorbitan fatty acid esters, granted as British Patent GB573789 in 1945, marking an early milestone in producing these compounds through ethoxylation of sorbitan esters with ethylene oxide. The patent detailed methods to introduce oxyethylene groups onto unesterified hydroxyls of sorbitan partial esters using fatty acids of 12 to 16 carbon atoms, enabling the creation of stable, water-dispersible surfactants.^[82] These innovations were driven by wartime needs for reliable emulsifiers in textiles and food processing, where shortages of natural materials like lecithin prompted the shift to synthetic options. The first commercial synthesis of Tween 80, the oleic acid variant of the series, occurred around 1948, establishing it as a key product for oil-in-water emulsions.

Commercialization

Polysorbate 80 entered the market in the late 1940s through Imperial Chemical Industries (ICI), which submitted a food additive petition to the FDA in 1947 for its use as an emulsifier under the trade name Tween 80, alongside related sorbitan esters such as Spans and Arlacels.^[83] This approval facilitated rapid adoption in the food and pharmaceutical sectors during the 1950s, where it served as a versatile non-ionic surfactant for stabilizing emulsions in processed foods, oral medications, and injectables. Croda International later assumed a leading role following its 2006 acquisition of Uniqema from ICI, inheriting production and distribution of Tween-branded polysorbates.^[84] Post-World War II demand for cost-effective synthetic emulsifiers propelled its growth, particularly in the expanding processed food industry. Polysorbate 80 has been regulated as a food additive under 21 CFR 172.840 since the 1958 Food Additives Amendment, with prior-sanctioned status for uses predating September 6, 1958. Key milestones included its incorporation into the United States Pharmacopeia (USP) during the 1960s, establishing pharmaceutical-grade standards for purity and consistency, and its broader integration into vaccine formulations in the 1970s and 1980s to improve antigen solubility and emulsion stability in products like influenza and hepatitis vaccines.^[79]^[85] In the 2020s, demand has grown in biopharmaceuticals, where polysorbate 80 serves as a stabilizer in certain formulations, including some vaccines. As of 2024, global production is approximately 4,300 metric tons annually to meet needs across industries. Leading suppliers include Croda International, BASF SE, and Evonik Industries, which provide high-purity grades tailored for pharmaceutical and food uses.^[86]^[87]

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POLYSORBATE 80 - Cosmetic Ingredient (INCI) - SpecialChem
Jul 17, 2023 · POLYSORBATE 80 ; /IUPAC Name: Sorbitan, mono-9-octadecenoate, poly(oxy-1,2-ethanediyl) derivs., (Z)- ; EINECS/ELINCS No: 500-019- ; REF No: 36902 ...
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What is Polysorbate 80? - Paula's Choice EU
Polysorbate 80?functions as a surfactant and texture-enhancing ingredient in cosmetics and is deemed safe for topical use. Learn more at Paula's Choice.?Missing: functions | Show results with:functions<|control11|><|separator|>
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Role of Emulsifiers and SPF Booster in Sunscreen Performance
While the commonly recommended range for Polysorbate® 80 is 1–3%, in F1–F3, an increased concentration of 5.4% was necessary to achieve adequate emulsion ...
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1 Final Report on the Safety Assessment of Polysorbates 20, 21, 40 ...
It is concluded that they are safe for use in cosmetics at present concentrations of use.
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Industry Perspective on the use and Characterization of ...
Polysorbate is a key excipient for biologics formulations to stabilize proteins. PS prevents protein losses through adsorption onto surfaces and protects ...Missing: benefits cosmetics spreadability
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Polysorbate 80: Uses, Interactions, Mechanism of Action - DrugBank
Identification. Brand Names. Clear Eyes Complete, Fluad Tetra, Refresh Optive Advanced, Viva-drops Lubricating Eye Drops. Generic Name ...Missing: trade abbreviations
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A Comprehensive List of All COVID-19 Vaccine Ingredients
May 20, 2021 · Polysorbate-80 (Tween 80) is used to stabilize and emulsify the vaccine. It is used in many other vaccines in the U.S., including tetanus ...
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The Role of Polysorbate 80 in Stabilizing Vaccine Formulations
Oct 19, 2025 · It acts as an emulsifier, ensuring that oil-in-water or water-in-oil emulsions remain stable, and as a solubilizer, helping to keep other ...
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[PDF] Kolliphor® PS 80 | BASF Pharma
In addition to these robust functionalities, Kolliphor® PS 80 is also a non-ionic surfactant and oil-in-water emulsifier that offers broad pH range.Missing: properties | Show results with:properties
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Polysorbate 80 (PF) Drops - Uses, Side Effects, and More
This medication is used to relieve dry, irritated eyes. Common causes for dry eyes include wind, sun, heating/air conditioning, computer use/reading, ...
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Effect of Polysorbate 80 Concentration on Thermal and ... - NIH
Higher temperature can lead to degradation of Polysorbate 80 and increase the peroxide content, as demonstrated by Ha et al.Missing: ethoxylation catalyst
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Chemical structure of commonly used surfactants polysorbate 80 (top...
The polysorbate concentration for most biologic formulations ranges from 0.004-0.1% (w/v) to protect against either aggregation and/or adsorption [8]. ...
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Polysorbate-Based Drug Formulations for Brain-Targeted ... - MDPI
PSs have been used as emulsifiers and solubilizers for hydrophobic drugs and as protein-stabilizing agents [19]. For example, PS 80 was used as a stabilizer ...
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Alternative drug formulations of docetaxel: a review - PubMed
The anticancer drug docetaxel (Taxotere) is formulated in the nonionic surfactant polysorbate 80 (Tween 80). Early in the clinical development of docetaxel, ...
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Extensive Characterization of Polysorbate 80 Oxidative Degradation ...
At 25°C, which is similar to room temperature commonly used during large-scale manufacturing, all the mono-esters and poly-esters from PS-80 were completely ...Missing: ethoxylation catalyst
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Peroxide formation in polysorbate 80 and protein stability - PubMed
We demonstrated that peroxides can be easily generated in neat polysorbate 80 in the presence of air during incubation at elevated temperatures.Missing: degradation studies
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[PDF] Polysorbate 80 - USP-NF
be examined. thickness 5 µm. Analysis: Titrate the Sample solution with 0.1 N potassium. Temperature hydroxide or 0.1 N sodium hydroxide until the pink color.
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The measurement and control of high-risk host cell proteins for ... - NIH
PSs are composed of a hydrophilic head group of ethoxylated sorbitan or isosorbide and a lipophilic fatty acid (FA) tail connected via an ester bond (Figure 1).
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Impact of Media Components on CQAs of Monoclonal Antibodies
Sep 1, 2017 · These chemicals are typically used to reduce the shear stress generated in stirred cultures and by pipette manipulation. Pluronic F-68 and Tween ...
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[PDF] 10% POLYSORBATE 80 - Thermo Fisher Scientific
Polysorbate 80 helps disperse the hydrophobic tightly-clumped mycobacterial cells from large aggregates to individual bacilli, maximizing the detection of ...
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[PDF] Pharmaceutical Microbiology Manual - FDA
Aug 25, 2020 · For the A. brasiliensis. ATCC 16404 culture, use sterile saline containing 0.05% polysorbate 80. Alternatively, cultures may be grown in a ...
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https://www.biopharminternational.com/view/impact-media-components-cqas-monoclonal-antibodies
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Polysorbate 80: A Versatile Emulsifier for Pharmaceuticals, Food ...
Polysorbate 80 is used in **agriculture, coatings, and chemical formulations** as a **wetting agent, dispersant, and stabilizer** to enhance product performance ...
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US20170183522A1 - Pigment-based inkjet inks - Google Patents
Polysorbate 20, Polysorbate 60, and Polysorbate 80 are shown by example below, as follows: ... Ink & Chem Inc Pigment dispersion for aqueous recording ...
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Polyoxyethylene sorbitan monooleate - PubChem - NIH
Oct 7, 1991 · Polysorbate 80 is an excipient that is used to stabilize aqueous formulations of medications for parenteral administration or vaccinations. A ...
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Fast and sensitive determination of Polysorbate 80 in solutions ...
A fast and sensitive method has been developed for the specific determination of Polysorbate 80 (Tween 80) in liquid formulations in the presence of proteins ...
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Oxidation of polysorbates – An underestimated degradation pathway?
Dec 15, 2023 · Despite their benefits of low toxicity and high biocompatibility, specific factors are influencing the intrinsic stability of polysorbates, ...
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Influence of Polysorbate 80 on the Larvicidal and Ecotoxicological ...
The system was developed using a low-energy oil-in-water emulsification method, relying exclusively on water and polysorbate 80-both nontoxic, biodegradable, ...
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Use of Span 80 and Tween 80 for blending gasoline and alcohol in ...
Span 80 and Tween 80 are biodegradable surfactants that can be added to blended fuels such as hydrated bioethanol–gasoline and methanol–gasoline.Research Paper · 2. Material And Methods · 3. Results And Discussion
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Profiling Active Enzymes for Polysorbate Degradation in ...
May 25, 2021 · Polysorbate is widely used to maintain stability of biotherapeutic proteins in pharmaceutical formulation development.
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https://pmc.ncbi.nlm.nih.gov/articles/PMC12333368/
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NTP Toxicology and Carcinogenesis Studies of Polysorbate 80 ...
Polysorbate 80 is a nonionic surfactant used widely as an additive in foods, pharmaceutical preparations, and cosmetics as an emulsifier, dispersant, ...Missing: chronic | Show results with:chronic
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Assessment of hydroxypropyl methylcellulose, propylene glycol ...
Results: In the rat fertility and rat teratology studies, PS80, PG, and HPβCD did not exhibit toxicity, when compared with MC. Similarly, in the rabbit ...
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[PDF] Members of the Sorbitan Fatty Acid Esters and the FROM
May 20, 2005 · The polysorbates have numerous uses in industry, research, pharmacy, and food production. They have been approved by the Food and Drug ...Missing: pharmaceuticals | Show results with:pharmaceuticals<|control11|><|separator|>
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[PDF] Safety Assessment of Polysorbates as Used in Cosmetics
Feb 20, 2015 · Polysorbate 80 produced a concentration-dependent suppression of DNA ... CIR safety data test summary: Polysorbate 80.' 362. LEO WINTER ...
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Oxidation of polysorbates – An underestimated degradation pathway?
Jan 1, 2025 · In this review, we provide an overview of the current knowledge on polysorbates with a focus on oxidative degradation.
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Metal-induced oxidation of polysorbate 80 in the presence of ...
Here, we present mechanistic studies on metal-induced PS80 oxidation in the presence of hydrogen peroxide in acetate buffer.
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Hypersensitivity reaction to human papillomavirus vaccine due ... - NIH
May 8, 2012 · Intradermal test with Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin tests with the bivalent vaccine were ...
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Polyethylene Glycol and Polysorbate 80 Skin Tests in the Context of ...
Apr 28, 2023 · Polyethylene glycol and polysorbate 80 skin tests in the context of an allergic risk assessment for hypersensitivity reactions to anti-SARS-CoV-2 mRNA vaccines.
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Macromolecules in polysorbate 80 for injection: an important cause ...
Jul 18, 2022 · Theoretically, 1 mol of polysorbate 80 can be synthesized from 1 mol of sorbitol, 20 mol of ethylene oxide, and 1 mol of oleic acid [13].
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Threshold for Anaphylactoid Reaction to Polysorbate 80 in Canines
Mar 25, 2022 · This study observed that impurities including free oleic acid, hydrogen peroxide, and ethylene oxide may trigger anaphylactoid reactions.
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Polysorbates, Biotherapeutics, and Anaphylaxis: A Review
This study demonstrated that PS-80 can cause severe nonimmunologic anaphylactoid reactions. Sun et al. evaluated the sensitization effect of PS-80 from ...
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Safety of Polysorbate 80 in the Oncology Setting
May 23, 2018 · Enzyme-linked immunosorbent assays have shown that polysorbate 80 could activate the complement system, a multiprotein immune mechanism.
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[PDF] Polysorbate 80 Monograph - USP-NF
May 1, 2016 · thickness 0.5 µm each mole of sorbitol and sorbitol anhydrides. Temperatures. IDENTIFICATION. Injection port: 250°. • A. It meets the ...Missing: physical chemical
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Polysorbate 80 | USP
The Polysorbate 80 monograph will be incorporated into and become official with the First Supplement to USP 40–NF 35. Should you have any questions about the ...
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[PDF] polysorbate 20 degradation in biotherapeutic formulations ... - FDA
Polysorbate 80 (PS80) and polysorbate 20 (PS20) are the most commonly used surfactants in formulations to stabilize therapeutic proteins against interfacial.
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Tween™ 80 - Croda Industrial Specialties
Tween 80 is an ethoxylated sorbitan ester based on a natural fatty acid (oleic acid). This ethoxylate is highly effective at forming oil in water emulsions.
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GB573789A - Improvements in or relating to ... - Google Patents
The usual fatty acids are used, preferably of 12 to 16 carbon atoms. Ethylene oxide is used to introduce the oxyethylene groups on to the unesterified hydroxyls ...Missing: GB573789 | Show results with:GB573789
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https://www.fda.gov/media/119754/download
... 80 I II 10/18/1951 DIAMOND SHAMROCK CHEM CORP DIPHENYLPYRALINE (THIS D FORMERLY HELD BY NOPCO CHEM. CO) 81 I II 8/11/1950 NATIONAL STARCH AND CHEMICAL CO ...
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[PDF] Celebrating 50 years as a public company
Croda acquires Uniqema from ICI, creating a chemical company with sales of nearly £1 billion. The Uniqema acquisition brought many new products such as the.
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Vaccine Adjuvants: from 1920 to 2015 and Beyond - PMC - NIH
Apr 16, 2015 · Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities.
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Polysorbate 80: Competitive Landscape and Growth Trends 2025 ...
Rating 4.8 (1,980) Mar 25, 2025 · Global production is estimated at 250 million kilograms annually, with a market value exceeding $1.5 billion USD. Concentration varies ...
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Polysorbate-80 Market Trends & Innovations 2024-2035
Jan 28, 2025 · The global Polysorbate-80 market is estimated to be worth USD 425.4 million in 2025 and is projected to reach a value of USD 803.1 million by 2035, expanding ...