Polysorbate 80

Identification

Name
Polysorbate 80
Accession Number
DB11063
Type
Small Molecule
Groups
Approved
Description

Polysorbate, a substance formulated by the reaction of sorbitan fatty acid ester (a nonionic surfactant) with ethylene oxide), is used in many foreign countries, including the U.S. and the EU, where it acts as an emulsifier, a solubilizer in many foods, including bread, cake mix, salad dressing, shortening oil and chocolate [18].

Polysorbate 80 is a hydrophilic nonionic surfactant. It is utilized as a surfactant in soaps and cosmetics and also as a lubricant in eye drops. In food or pharmaceutical products, it can act as an emulsifier. Polysorbate 80 is an excipient that is used to stabilize aqueous formulations of medications for parenteral administration or vaccinations [15].

A solubilizing agent acts as a surfactant and increases the solubility of one agent in another. A substance that would not normally dissolve in a particular solution is able to dissolve with the use of a solubilizing agent [15].

It is also known as an emulsifier, which helps ingredients mix together and prevent separation, and water-containing small amounts of salts, and is included in several vaccines licensed in the USA [9].

Synonyms
  • polyoxyethylene-sorbitan-20 mono-oleate
  • Tween 80
Active Moieties
NameKindUNIICASInChI Key
Sorbitanunknown6O92ICV9RU12441-09-7JNYAEWCLZODPBN-JGWLITMVSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AvitearsSolution / drops10 mg/1mLTopicalPinnacle Science, LLc2009-07-17Not applicableUs
PolysorbateSolution0.8 %Ophthalmic; TopicalEberth Pharmaceuticals Inc1994-12-31Not applicableCanada
VivaSolution / drops100 mg/10mLOphthalmicDakota Laboratories, Llc1987-02-19Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Clear Eyes Complete 7 Symptom ReliefPolysorbate 80 (1.25 mL/1mL) + Hypromellose (.5 mL/1mL) + Naphazoline hydrochloride (.0625 mL/1mL) + Zinc sulfate, unspecified form (.625 mL/1mL)LiquidOphthalmicPrestige Brands Holdings, Inc.2010-03-01Not applicableUs
Clear Eyes Complete 7 Sympton ReliefPolysorbate 80 (1.25 mg/1mL) + Hypromellose (.5 mg/1mL) + Naphazoline hydrochloride (.0625 mg/1mL) + Zinc sulfate, unspecified form (.625 mg/1mL)LiquidOphthalmicPrestige Brands Holdings, Inc.2013-06-12Not applicableUs
OtovelPolysorbate 80 (6250 ug/0.25mL) + Ciprofloxacin (872.5 ug/0.25mL) + Fluocinolone acetonide (62.5 ug/0.25mL)For solutionAuricular (otic)Arbor Pharmaceuticals2016-04-29Not applicableUs
REFRESH OPTIVE AdvancedPolysorbate 80 (0.5 %) + Carboxymethylcellulose sodium (0.5 %) + Glycerin (1.0 %)SolutionOphthalmicAllergan2013-03-06Not applicableCanada
REFRESH OPTIVE AdvancedPolysorbate 80 (5 mg/1mL) + Carboxymethylcellulose sodium (5 mg/1mL) + Glycerin (10 mg/1mL)Solution / dropsOphthalmicAllergan2011-11-30Not applicableUs
REFRESH OPTIVE AdvancedPolysorbate 80 (5 mg/1mL) + Carboxymethylcellulose sodium (5 mg/1mL) + Glycerin (10 mg/1mL)Solution / dropsOphthalmicAllergan2013-01-15Not applicableUs
Refresh Optive Advanced SensitivePolysorbate 80 (0.5 %) + Carboxymethylcellulose sodium (0.5 %) + Glycerin (1.0 %)EmulsionOphthalmicAllergan2014-10-14Not applicableCanada
REFRESH OPTIVE Mega-3Polysorbate 80 (5 mg/1mL) + Carboxymethylcellulose sodium (5 mg/1mL) + Glycerin (10 mg/1mL)Solution / dropsOphthalmicAllergan2017-05-30Not applicableUs
Rohto Beauty SecretPolysorbate 80 (2 mg/1mL) + Naphazoline hydrochloride (.12 mg/1mL)LiquidOphthalmicThe Mentholatum Company2017-10-01Not applicableUs
Rohto CoolPolysorbate 80 (2 mg/1mL) + Naphazoline hydrochloride (.12 mg/1mL)LiquidOphthalmicRohto-Mentholatum (Vietnam) Co. Ltd.2012-02-01Not applicableUs
International/Other Brands
Tween-80
Categories
UNII
6OZP39ZG8H
CAS number
9005-65-6
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

It is used as a solubilizer, antimicrobial preservative and disinfectant [16].

Pharmacodynamics

Polysorbates are widely used to protect biological drug products from protein unfolding, aggregation, and precipitation during both shipping and handling. The polysorbates are amphipathic, nonionic surfactants made of fatty acid esters of polyoxyethylene sorbitan. Polysorbate 80 is one of the most common surfactants currently used in the formulation of protein-based biopharmaceuticals [6].

Mechanism of action

Polysorbate 80 is one of the primary components of protein formulations. This drug inhibits interfacial damage of the protein molecule that undergoes mechanical stress during shipping and handling. Polysorbate 80 also affects the formulation photostability. Exposure to light of polysorbate 80 aqueous solution results in peroxide generation, which in turn may lead to oxidation of the susceptible amino acid residues in the protein molecule [6].

One study on rats found that Polysorbate 80 increased apical to basolateral membrane permeability of digoxin in Caco-2 cells suggesting that Ps 80 is an in vitro inhibitor of P-glycoprotein. It concluded that PS 80 may influence in vivo absorption of P-gp substrates, and this could be translated to human applications [5].

Absorption

Poorly absorbed [18].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Polysorbates undergo degradation by auto-oxidation, producing reactive peroxides, in addition to hydrolysis [13]. Exposure to light of polysorbate 80 aqueous solution leads autoxidation of the alkyl polyoxyethylene chain leading to the production of hydroperoxide derivatives. The peroxides cause oxidative damage to the protein molecule that makes up the formulation. The residual peroxides and the rate of peroxide generation as a result of light exposure are found to vary for polysorbate 80 of different grades/from different sources [6].

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Acute oral toxicity (LD50): 25000 mg/kg in Mouse [MSDS]

In general, study results of the polysorbates demonstrated no carcinogenicity and genotoxicity. In repeated-dose toxicity studies, diarrhea was observed as the major symptom of toxicity [18]. Some studies, however, show conflicting findings.

In a 2-year dietary study of polysorbate 80 in rats, a higher incidence of adrenal medullary pheochromocytomas was found, mainly in male rats [18].

Polysorbate 80 is used as a solubilizing agent in IV infusions of the antiarrhythmic drug amiodarone. Rare case reports of liver toxicity have been published suggesting polysorbate 80 may contribute to liver toxicity with the IV formulation of amiodarone. The package labeling of amiodarone warns that polysorbate 80 is also known to leach DEHP (dioctyl phthalate) from PVC and dosing recommendations must be followed closely [15].

It was found that maternal toxicities such as loose stool, suppression of weight gain and reduced intake were seen, and poor lactation was noted in some studies of mother rats administered 7.5% solutions of polysorbates [18].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Coors EA, Seybold H, Merk HF, Mahler V: Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol. 2005 Dec;95(6):593-9. doi: 10.1016/S1081-1206(10)61024-1. [PubMed:16400901]
  2. Sun W, Xie C, Wang H, Hu Y: Specific role of polysorbate 80 coating on the targeting of nanoparticles to the brain. Biomaterials. 2004 Jul;25(15):3065-71. doi: 10.1016/j.biomaterials.2003.09.087. [PubMed:14967540]
  3. Zhao YM, Xia AX, Wei YH, Ruan YP, Li FZ: [Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrier]. Yao Xue Xue Bao. 2010 Oct;45(10):1312-6. [PubMed:21348312]
  4. van Tellingen O, Beijnen JH, Verweij J, Scherrenburg EJ, Nooijen WJ, Sparreboom A: Rapid esterase-sensitive breakdown of polysorbate 80 and its impact on the plasma pharmacokinetics of docetaxel and metabolites in mice. Clin Cancer Res. 1999 Oct;5(10):2918-24. [PubMed:10537361]
  5. Zhang H, Yao M, Morrison RA, Chong S: Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res. 2003 Sep;26(9):768-72. [PubMed:14560928]
  6. Wang CX, Huang LS, Hou LB, Jiang L, Yan ZT, Wang YL, Chen ZL: Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model. Brain Res. 2009 Mar 19;1261:91-9. doi: 10.1016/j.brainres.2009.01.011. Epub 2009 Jan 20. [PubMed:19401168]
  7. Polysorbate 80 [Link]
  8. Code of Federal Regulation [Link]
  9. Common Ingredients in U.S. Licensed Vaccines [Link]
  10. NTP Toxicology and Carcinogenesis Studies of Polysorbate 80 (CAS No. 9005-65-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). [Link]
  11. Polysorbate 80 and Helicobacter pylori: a microbiological and ultrastructural study [Link]
  12. Food Emulsifier Polysorbate 80 Increases Intestinal Absorption of Di-(2-Ethylhexyl) Phthalate in Rats [Link]
  13. Polysorbates, peroxides, protein aggregation, and immuno- genicity – a growing concern. [Link]
  14. In uence of excipients on drug absorption via modulation of intestinal transporters activity [Link]
  15. Polysorbate 80 [Link]
  16. Overview of pharmaceutical excipients used in tablets and capsules [Link]
  17. Effect of Polysorbate 80 Quality on Photostability of a Monoclonal Antibody [Link]
  18. Evaluation reports of Polysorbates [Link]
External Links
PubChem Substance
347911102
Wikipedia
Polysorbate_80
AHFS Codes
  • 52:13.00* — Artificial Tears
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentDry Eye Syndromes1
4CompletedTreatmentDry Eye Syndromes1
4CompletedTreatmentPsoriasis / Sleep Apnea, Obstructive1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Solution / dropsTopical10 mg/1mL
LiquidOphthalmic
For solutionAuricular (otic)
SolutionOphthalmic; Topical0.8 %
SolutionOphthalmic
Solution / dropsOphthalmic
EmulsionOphthalmic
Solution / dropsOphthalmic100 mg/10mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8932610No2010-03-242030-03-24Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)-20.556MSDS
boiling point (°C)100MSDS
water solubilityEasily soluble in cold water, hot waterMSDS
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Drug created on December 03, 2015 09:51 / Updated on September 18, 2018 23:02