Macrogols, solid grades

• BPMacrogols
• JPMacrogol 4000; Macrogol 6000; Macrogol 20000
• Ph. Eur.Macrogols
• USP–NFPolyethylene Glycol

PEG 1000–35 000; PEG 1500; PEG 3350; PEG 4000; PEG 6000; PEG 8000; polyethylene glycol; polyoxyethylene glycol; Carbowax; Lutrol E; Pluriol E; E1521

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

HOCH2(CH2OCH2)nCH2OH · about 950–35 000 (grade-dependent average)

Semi-solid base, emollient, Lubricant, Plasticiser, Binder

Typical concentrations: — · Dosage forms: Solid, Semi-solid

Solid macrogols are used as water-soluble suppository bases (alone or blended, typically making up most of the base), in ointment bases blended with liquid grades, as binders and soluble lubricants in tablets, as carriers in solid dispersions and melt granulation, and as plasticisers and polishing agents in film coating. Grades such as PEG 3350 and PEG 4000 are also used therapeutically as osmotic laxatives.

White or almost white, waxy or paraffin-like solids supplied as flakes, granules or powder; grades around PEG 1000 are soft, low-melting solids. They are odourless or nearly so.

Melting range

rises with molecular weight: about 37–40 °C (PEG 1000) to about 60–63 °C (PEG 8000 and above)

Solubility

soluble in water (solubility falls with increasing molecular weight), dichloromethane and acetone; practically insoluble in ether, fixed oils and mineral oil

pH

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

Hygroscopicity

decreases as molecular weight increases

Chemically stable and do not support microbial growth. Like liquid grades they can autoxidise on heating in air, forming peroxides and aldehydes; avoid prolonged heating of the melt. Store in well-closed containers in a cool, dry place.

Oxidising agents and reactive impurities (peroxides, formaldehyde) can affect sensitive drugs. Phenols such as tannic acid and salicylic acid can soften or liquefy macrogol bases; some antibiotics lose activity and paraben efficacy may be reduced. Suppositories may become brittle with certain drugs, and the bases can interact with some plastics.

Made by base-catalysed polymerisation of ethylene oxide, controlled to give the required average molecular weight; the product is then flaked, milled or prilled.

Low oral toxicity and poorly absorbed; large doses act as osmotic laxatives. Suppository bases may cause rectal irritation because they draw water from the mucosa. Hypersensitivity, including rare anaphylaxis, to polyethylene glycols has been reported. Topical use on extensive burns can lead to absorption and nephrotoxicity.

Observe normal precautions for the quantity handled. Avoid generating dust; eye protection, gloves and a dust mask are recommended.

Permitted food additives in Europe (E1521) and in the USA under specified conditions (21 CFR 172.820). Included in the FDA Inactive Ingredient Database (oral capsules, solutions and tablets; rectal, topical and vaginal preparations; injections) and in parenteral and non-parenteral medicines licensed in Europe.

Macrogol 400 (PEG 400); polyethylene oxide; poloxamers; macrogol stearates.

The consistency of macrogol ointment and suppository bases is adjusted by blending liquid and solid grades. Macrogol suppositories dissolve rather than melt, so they need not be stored refrigerated, but they should be moistened with water before insertion. In solid dispersions the drug may crystallise on storage, so physical stability must be checked.