Monographs: Pharmaceutical substances: Polysorbata 20, 60, 80 - Polysorbates 20, 60, 80

Chemical names

Polysorbate 20: Polyoxyethylene 20 sorbitan monolaurate; sorbitan monododecanoate, poly(oxy-1,2-ethanediyl) derivatives; CAS Reg. No. 9005-64-5.

Polysorbate 60: Polyoxyethylene 20 sorbitan monostearate; sorbitan monooctadecanoate, poly(oxy-1,2-ethanediyl) derivatives; CAS Reg. No. 9005-67-8.

Polysorbate 80: Polyoxyethylene 20 sorbitan monooleate; sorbitan mono[(Z)-9-octadecenoate], poly(oxy-1,2-ethanediyl) derivatives; CAS Reg. No. 9005-65-6.

Description. Polysorbates 20 and 80 are yellowish or yellowish brown, oily liquids. Polysorbate 60 is a gelatinous mass, and a clear liquid above 25 °C.

Solubility. Miscible with water, ethanol (~750 g/l) TS, methanol R, and ethyl acetate R; practically insoluble in fatty oils and in liquid paraffin R.

Category. Nonionic surfactant.

Storage. Polysorbates should be kept in tightly closed containers, protected from light.

Additional information. Relative densities of Polysorbates 20 and 60 = about 1.10; Polysorbate 80 = about 1.08.

Requirements

Definition. Polysorbates are mixtures of partial fatty acid esters of sorbitol and its anhydrides, copolymerized with approximately 20 moles of ethylene oxide for each mole of sorbitol and sorbitol anhydride.

In Polysorbate 20 the fatty acid is lauric acid which may contain other fatty acids. In Polysorbate 60 the fatty acid is stearic acid which may contain other fatty acids, especially palmitic acid. In Polysorbate 80 the fatty acid is oleic acid.

Identity tests

A. A mixture of 6 volumes of Polysorbates and 4 volumes of water yields a gelatinous mass at room temperature as well as at lower temperatures.

B. Dissolve 0.1 g in 5 ml of chloroform R, and add 0.1 g of potassium thiocyanate R and 0.1 g of cobalt(II) nitrate R. Stir with a glass rod; the solution becomes blue.

Heavy metals. Use 1.0 g for the preparation of the test solution as described under 2.2.3 Limit test for heavy metals, Procedure 3; determine the heavy metals content according to Method A; not more than 10 μg/g.

Acid value. Not more than 2.0.

Hydroxyl value. Use Method B.

Polysorbate 20: 96-108.

Polysorbate 60: 81-96.

Polysorbate 80: 65-80.

Iodine value.

Polysorbates 20 and 60: not more than 5.0.

Polysorbate 80: 18-24.

Saponification value.

Polysorbate 20: 40-50.

Polysorbate 60: 45-55.

Polysorbate 80: 45-55.

Reducing impurities. Dissolve 2 g in 25 ml of hot water and add 25 ml of sulfuric acid (~100 g/l) TS and 0.1 ml of ferroin TS. Titrate with ceric ammonium nitrate (0.01 mol/l) VS, shaking continuously, until the colour change from red to greenish blue persists for 30 seconds. Repeat the procedure without the Polysorbates being examined and make any necessary corrections. Consumption of ceric ammonium nitrate (0.01 mol/l) VS:

Polysorbates 20 and 60: not more than 2.0 ml

Polysorbate 80: not more than 5.0 ml.

Sulfated ash. Use 2.0 g; not more than 2.5 mg/g.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using 1 g; the water content is not more than 30 mg/g.

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