Polysorbate 80

• BPPolysorbate 80
• JPPolysorbate 80
• Ph. Eur.Polysorbate 80
• USP–NFPolysorbate 80

Crillet 4; Kolliphor PS 80; Montanox 80; polyoxyethylene 20 sorbitan monooleate; polysorbatum 80; PEG-20 sorbitan monooleate; Tween 80; E433

Polyoxyethylene 20 sorbitan monooleate · [9005-65-6]

C64H124O26 (approximate) · ≈ 1 310

Surfactant, emulsifier

Typical concentrations: 1–15% emulsifier · 1–10% solubiliser · 0.1–3% wetting · Dosage forms: Liquid, Semi-solid, Sterile (parenteral/ophthalmic)

The most widely used polysorbate in medicines: an emulsifier, solubiliser, wetting agent and stabiliser in oral liquids, topical products and parenteral formulations, including injectable products of poorly soluble drugs (for example amiodarone and docetaxel concentrates), vaccines and biologics. In protein and antibody products it is typically used at about 0.001–0.1% w/v to prevent aggregation at interfaces. Typical concentrations: emulsifying agent used alone in oil-in-water emulsions 1–15%, or 1–10% when combined with lipophilic emulsifiers; solubilising agent for poorly soluble drugs in aqueous vehicles 1–10%; wetting agent for insoluble solids 0.1–3%.

A mixture of partial oleic acid esters of sorbitol and its anhydrides copolymerised with about 20 moles of ethylene oxide per mole of sorbitol. Oleic acid is the main fatty acid, with smaller amounts of linoleic, palmitic and stearic acids. It is a yellow to amber, oily liquid.

Physical form

yellow to amber, oily liquid at 25 °C with a characteristic odour and a warm, somewhat bitter taste

HLB

about 15.0

Saponification value

about 45–55

Density

about 1.08 g/cm³

Viscosity

about 400–425 mPa·s (25 °C)

Solubility

soluble in water and ethanol; practically insoluble in fatty oils and liquid paraffin

Polysorbates are stable to electrolytes and weak acids and bases; strong acids and bases cause gradual saponification. The oleic-acid esters in particular are susceptible to autoxidation, forming peroxides and degrading on exposure to light, heat and metal ions. They are hygroscopic and should be stored in a well-closed, well-filled container, protected from light, in a cool, dry place; nitrogen blanketing helps limit oxidation.

Discoloration or precipitation occurs with various substances, especially phenols, tannins and tars. They reduce the antimicrobial activity of many preservatives, particularly parabens, by micellar binding, and peroxide impurities can oxidise sensitive drugs and proteins.

Prepared by esterifying sorbitol and its anhydrides (mainly sorbitan) with oleic acid and then reacting the product with about 20 moles of ethylene oxide per mole of sorbitol.

Generally regarded as non-toxic and non-irritant in oral and topical use. After intravenous administration it has been associated with hypersensitivity and infusion reactions, and a vitamin E injection containing polysorbates was linked to serious adverse effects and deaths in low-birth-weight infants. JECFA and EFSA have set a group ADI of 25 mg/kg body weight per day for polysorbates 20, 40, 60, 65 and 80.

Observe normal precautions for the quantity handled. Eye protection and gloves are recommended.

Accepted as a food additive in Europe (E433). Included in the FDA Inactive Ingredient Database (IM, IV and SC injections; oral capsules, solutions, suspensions and tablets; ophthalmic, topical and other preparations) and in parenteral and non-parenteral medicines licensed in Europe.

Polysorbate 20; polysorbate 60; polyoxyl 35 castor oil; sorbitan monooleate.

The unsaturated oleate chain makes polysorbate 80 prone to oxidation; peroxide content varies between grades and lots and can degrade oxidation-sensitive drugs and proteins, so low-peroxide (often plant-derived, high-purity) grades are preferred for parenterals and biologics. Like other surfactants, it extracts DEHP from PVC administration sets.