Polysorbate
Polysorbates are a family of synthetic nonionic surfactants consisting of polyoxyethylene sorbitan esters of fatty acids, such as lauric, palmitic, stearic, or oleic acid, derived from the dehydration of sorbitol (a sugar alcohol) and subsequent ethoxylation.[1] These compounds, often referred to by their trade names like Tween, are amphipathic molecules that exhibit both hydrophilic and lipophilic properties, enabling them to stabilize emulsions and dispersions effectively.[2] Common variants include polysorbate 20 (derived from lauric acid), polysorbate 40 (palmitic acid), polysorbate 60 (stearic acid), and polysorbate 80 (oleic acid), each differing in their fatty acid, with approximately 20 ethylene oxide units.[2] In the food industry, polysorbates function as emulsifiers, stabilizers, and solubilizers, permitting the uniform mixing of oil and water-based ingredients in products such as ice cream, salad dressings, and baked goods, with approved usage levels up to 0.4% in many formulations.[3] They are also widely employed in cosmetics and personal care products as surfactants to enhance texture, foaming, and solubility, often at concentrations of 0.1% to 25%.[1] In pharmaceuticals, particularly biotherapeutics, polysorbates like polysorbate 80 and 20 serve as critical stabilizers to protect proteins from aggregation, adsorption to surfaces, and denaturation during manufacturing, storage, and administration, making them essential in vaccines, injectables, and monoclonal antibody formulations.[4][5] Regulatorily, polysorbates are recognized as safe for their intended uses by agencies such as the U.S. Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA), with exemptions from pesticide residue tolerances when used as inert ingredients and affirmative listings as direct food additives under 21 CFR 172.836 and 172.840.[1][3] Despite their utility, concerns regarding their oxidative degradation—leading to potential impurities like peroxides—and hypersensitivity reactions in sensitive populations have prompted ongoing research into alternatives and improved stabilization strategies.[6]Chemistry
Structure
Polysorbates are a class of nonionic surfactants derived from ethoxylated sorbitan esters of fatty acids.[7] The core structure features a sorbitan ring, the dehydrated form of sorbitol with molecular formula \ce{C6H12O5}, to which polyoxyethylene chains—typically comprising about 20 ethylene oxide units—are attached at the available hydroxyl groups through ether bonds, while a single fatty acid is esterified at one position.[7] This ring structure arises from the intramolecular dehydration of sorbitol, resulting in a five-membered cyclic ether with four hydroxyl groups available for modification.[7] The molecular architecture of polysorbates confers an amphiphilic character, with the polyoxyethylene chains serving as the hydrophilic head and the esterified fatty acid chain acting as the hydrophobic tail, enabling their role as emulsifiers.[7] The general formula representation extends the sorbitan core by (\ce{OCH2CH2})_n where n \approx 20, combined with \ce{RCOO-} where R denotes the alkyl chain of the fatty acid.[7] Variations in isomerism stem from the multiple hydroxyl positions on the sorbitan ring, leading to a complex mixture of positional and stereoisomers during ethoxylation and esterification, as well as contributions from both 1,4-sorbitan and 1,6-isosorbide forms.[8][7]Types and properties
Polysorbates are a family of nonionic surfactants consisting of sorbitan esters of various fatty acids ethoxylated with approximately 20 moles of ethylene oxide. The most common variants are distinguished by the fatty acid component, which influences their physical and chemical properties. The primary types include Polysorbate 20, derived from lauric acid (C12:0); Polysorbate 40, from palmitic acid (C16:0); Polysorbate 60, from stearic acid (C18:0 saturated); and Polysorbate 80, from oleic acid (C18:1 unsaturated). These are widely known by their trade names Tween 20, Tween 40, Tween 60, and Tween 80, respectively, marketed by Croda International Plc.[9][10] Key properties vary by type, as summarized below:| Type | Fatty Acid | HLB Value | Appearance | Solubility | Density (g/cm³) | Approximate Molar Mass (g/mol) |
|---|---|---|---|---|---|---|
| Polysorbate 20 | Lauric (C12) | 16.7 | Clear yellow to amber liquid | Water, ethanol, methanol | 1.095 | 1228 |
| Polysorbate 40 | Palmitic (C16) | 15.6 | Viscous oily liquid or paste | Water, methanol | 1.05 | ~1280 |
| Polysorbate 60 | Stearic (C18 sat) | 14.9 | Waxy solid or semigel at room temperature | Water, ethyl acetate | ~1.02 | ~1310 |
| Polysorbate 80 | Oleic (C18 unsat) | 15.0 | Amber viscous liquid | Water, ethanol | 1.06–1.10 | 1310 |