Polysorbate 20
Polysorbate 20, also known as polyoxyethylene (20) sorbitan monolaurate or Tween 20 (CAS number 9005-64-5), is a nonionic surfactant and emulsifying agent derived from the partial esterification of sorbitol and its anhydrides with lauric acid, followed by condensation with approximately 20 moles of ethylene oxide.[1] It appears as a lemon to amber-colored oily liquid at room temperature, with a faint characteristic odor, a density of about 1.095 g/mL, and high solubility in water, ethanol, and other polar solvents, but insolubility in mineral oil.[1] Chemically stable under neutral conditions and in the presence of electrolytes or weak acids and bases, it is sensitive to oxidation and hydrolysis by strong acids or bases.[1] It is widely used as an emulsifier, stabilizer, and solubilizer in food, pharmaceuticals, cosmetics, and biotechnology products.[2][3] Polysorbate 20 is generally recognized as safe (GRAS) by the FDA for intended uses in food and approved as an excipient in pharmaceuticals, with an acceptable daily intake (ADI) of 0–25 mg/kg body weight established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).[2][1]Chemical Characteristics
Structure and Nomenclature
Polysorbate 20, also known as polyoxyethylene (20) sorbitan monolaurate, is the IUPAC name for this non-ionic surfactant, reflecting its composition as a sorbitan ester ethoxylated with approximately 20 units of ethylene oxide.[1][4] The chemical formula is approximately C58H114O26, though this represents an idealized average, as Polysorbate 20 is a polydisperse mixture resulting from variable degrees of ethoxylation and the presence of sorbitol anhydrides in the backbone.[1][5] Common trade names include Tween 20 and Kolliphor PS 20; Tween 20 originated as part of the "Tween" series of surfactants developed by Imperial Chemical Industries (ICI) in the 1940s for emulsification applications.[1][6][7] Structurally, Polysorbate 20 features a sorbitan backbone—derived from the dehydration of sorbitol, a six-carbon sugar alcohol—that is esterified at one primary hydroxyl group with lauric acid, a 12-carbon saturated fatty acid providing the hydrophobic tail. Attached to the remaining hydroxyl groups of the sorbitan are polyoxyethylene chains totaling about 20 ethylene oxide units, forming the hydrophilic head that confers amphiphilic properties essential for its surfactant behavior.[1][8][9] The Hydrophile-Lipophile Balance (HLB) value of Polysorbate 20 is 16.7, classifying it as a highly hydrophilic emulsifier suitable for oil-in-water systems due to the dominance of the polar polyoxyethylene segments over the non-polar lauric acid chain.[1][4]Physical Properties
Polysorbate 20 is a clear, pale yellow to amber-colored viscous liquid at room temperature, often exhibiting a faint characteristic odor.[1] Its density is approximately 1.1 g/cm³ at 25°C.[10] The refractive index is 1.468 at 20°C.[1] Viscosity ranges from 370 to 430 cP at 25°C.[4] The boiling point exceeds 100°C, with decomposition occurring before boiling.[4] The flash point is >150 °C.[11] Polysorbate 20 exhibits high solubility in water (miscible up to high concentrations), ethanol, methanol, ethyl acetate, and dioxane, while it is insoluble in mineral oil and mineral spirits.[1] As a nonionic surfactant, Polysorbate 20 reduces the surface tension of water to approximately 37 mN/m at its critical micelle concentration (CMC) of 0.006–0.008% w/v (around 60 mg/L at 25°C).[12][4] This property arises from its high HLB value of 16.7, which favors oil-in-water emulsification.[4]Chemical Properties and Reactivity
Polysorbate 20 is a non-ionic surfactant that does not ionize in aqueous solutions, enabling broad compatibility with ionic and other charged species in formulations without disrupting electrostatic interactions.[1] It exhibits good stability in neutral to mildly acidic and alkaline conditions, typically within a pH range of 4 to 9, where it maintains its structural integrity during storage and use in biopharmaceutical and cosmetic applications.[13] Degradation primarily occurs through auto-oxidation of the ethylene oxide chains, generating peroxides, or hydrolysis of the ester linkages between the sorbitan and lauric acid moieties, yielding free fatty acids such as lauric acid.[14] These processes can compromise its emulsifying efficacy and lead to the formation of particulates in solutions over time. Oxidative degradation of Polysorbate 20 is particularly susceptible to environmental stressors including exposure to light, elevated temperatures, and trace metal ions like iron, which catalyze peroxidation reactions along the polyoxyethylene segments.[15] Hydrolytic breakdown is accelerated under enzymatic conditions, such as by residual lipases or esterases in biotherapeutic formulations, or in the presence of strong bases that cleave the ester bonds more rapidly.[16] These reactivity pathways highlight the need for controlled storage conditions, such as avoidance of metal contamination and light exposure, to preserve functionality. The critical micelle concentration (CMC) of Polysorbate 20 is approximately $5.5 \times 10^{-5} M in water at room temperature, marking the threshold for self-assembly into micelles that enhance the solubilization of hydrophobic substances through incorporation into their hydrophobic cores.[17] Due to the ethoxylation process in its synthesis, Polysorbate 20 displays polydispersity in the ethylene oxide chain length, with an average of 20 units per molecule but a distribution typically ranging from 12 to 25 units, which contributes to variability in micelle size and overall uniformity of behavior in solutions.[18]Production
Synthesis Methods
Polysorbate 20, also known as Tween 20, was developed in the 1940s by Imperial Chemical Industries (ICI) as part of the Tween series of nonionic surfactants to address post-World War II demands for effective emulsifiers in various industries.[7] The primary synthesis route involves a multi-step process starting with the acid-catalyzed dehydration of sorbitol to form sorbitan. This dehydration typically occurs at temperatures around 180°C using phosphoric acid as a catalyst, yielding primarily the 1,4-sorbitan isomer along with minor amounts of isosorbide.[19][20] The next step is the esterification of sorbitan with lauric acid to produce sorbitan monolaurate. This reaction is conducted under acidic conditions, such as with p-toluenesulfonic acid (p-TSA) as catalyst, at approximately 160°C, aiming for a fatty acid-to-sorbitol molar ratio near 1.1 to favor the monoester while minimizing higher esters.[21][22] Subsequently, sorbitan monolaurate undergoes base-catalyzed ethoxylation with approximately 20 moles of ethylene oxide (EO). This step employs a catalyst like sodium or potassium hydroxide at elevated temperatures of 150–200°C and pressures of 1–2 bar, resulting in a polyoxyethylene chain attached to the sorbitan laurate structure.[23] The key reactions can be represented as follows:-
Dehydration:
\ce{C6H14O6 ->[acid][\sim 180^\circ C] C6H12O5 + H2O}
(Sorbitol to sorbitan)[19] -
Esterification:
\ce{C6H12O5 + C11H23COOH ->[acid][\sim 160^\circ C] C6H11O5(COC11H23) + H2O}
(Sorbitan + lauric acid to sorbitan monolaurate)[21] -
Ethoxylation:
\ce{C6H11O5(COC11H23) + 20 CH2CH2O -> C6H11O5(COC11H23)(OCH2CH2)_{20}OH}
(Sorbitan monolaurate + 20 EO to Polysorbate 20)[23]