Macrogol 400 (PEG 400)

• BPMacrogols
• JPMacrogol 400
• Ph. Eur.Macrogols
• USP–NFPolyethylene Glycol

PEG 400; polyethylene glycol 400; macrogol 400; Carbowax 400; Kollisolv PEG 400; Lutrol E 400; polyoxyethylene glycol 400; α-hydro-ω-hydroxypoly(oxy-1,2-ethanediyl); E1521

α-Hydro-ω-hydroxypoly(oxy-1,2-ethanediyl) · [25322-68-3]

HOCH2(CH2OCH2)nCH2OH, n ≈ 8 · 380–420 (average)

Solvent, humectant, Semi-solid base, emollient

Typical concentrations: q.s. · Dosage forms: Liquid, Semi-solid

A water-miscible cosolvent and vehicle used in oral solutions, soft and hard capsule fills, parenteral injections (concentrations up to about 30% v/v are used), ophthalmic and topical preparations, and in ointment bases blended with solid macrogols. It is also used as a plasticiser in film coatings and as a solubiliser in self-emulsifying systems.

A clear, colourless or slightly yellowish, viscous, hygroscopic liquid with a slight characteristic odour and a slightly bitter, burning taste.

Density

≈ 1.12 g/cm³ at 25 °C

Freezing point

about 4–8 °C

Viscosity (dynamic, 20 °C)

about 105–130 mPa·s

pH

about 4.5–7.5 (5% w/v aqueous solution)

Refractive index

≈ 1.465 at 25 °C

Solubility

miscible with water, ethanol, acetone and other glycols; practically insoluble in fixed oils, mineral oil and fats

Chemically stable in air and in solution and does not support microbial growth. On exposure to air and heat it can autoxidise, forming peroxides, formaldehyde and formic acid that may degrade sensitive drugs; antioxidants may be added. Store in an airtight container, protected from light, in a cool place.

Can react with oxidising agents. Peroxide and aldehyde impurities may degrade susceptible drugs; the antibacterial activity of some antibiotics (for example penicillin and bacitracin) is reduced in polyethylene glycol bases, and preservative efficacy of parabens may be lowered. It can soften or dissolve some plastics and may affect cellulose ester membranes.

Made by base-catalysed polymerisation of ethylene oxide with water or a glycol as initiator, controlled to the required average chain length.

Low oral toxicity; large oral doses are laxative. Topical application to damaged skin or burns has been associated with absorption and nephrotoxicity. Concentrated parenteral solutions are hyperosmotic and can cause haemolysis or local irritation. Hypersensitivity to polyethylene glycols, though rare, has been reported.

Observe normal precautions for the quantity handled. Eye protection and gloves are recommended; spills are slippery and should be cleaned up promptly.

Polyethylene glycols are permitted food additives in Europe (E1521) and in the USA under specified conditions (21 CFR 172.820). Included in the FDA Inactive Ingredient Database (injections; ophthalmic, oral, rectal, topical and vaginal preparations) and in parenteral and non-parenteral medicines licensed in Europe.

Macrogol 300; macrogol 600; solid macrogols; propylene glycol; glycerin.

PEG 400 is a strong water-miscible solvent, so drugs dissolved in it may precipitate on dilution with water or in the gastrointestinal tract. Use low-peroxide grades for oxidation-sensitive drugs and keep stock containers tightly closed.