N-Methylpyrrolidone

• BPN-Methylpyrrolidone
• Ph. Eur.N-Methylpyrrolidone

NMP; 1-methyl-2-pyrrolidone; 1-methylpyrrolidin-2-one; N-methyl-2-pyrrolidinone; Pharmasolve

1-Methylpyrrolidin-2-one · [872-50-4]

UNII JR9CE63FPM · PubChem CID 13387

C5H9NO · 99.13

Solvent, humectant

Typical concentrations: — · Dosage forms: Sterile (parenteral/ophthalmic)

A powerful water-miscible solvent used in veterinary injections and in in-situ forming depot injections, where a biodegradable polymer such as poly(lactide-co-glycolide) is dissolved in NMP and precipitates on injection to form an implant. It is also used as a solubiliser and penetration enhancer in topical and transdermal products. The amount used is limited by its toxicity profile.

A clear, colourless to slightly yellow, hygroscopic liquid with a faint amine-like odour.

Boiling point

≈ 202 °C

Freezing point

≈ −24 °C

Density

≈ 1.03 g/cm³ at 25 °C

Solubility

miscible with water, ethanol, ether, chloroform, ethyl acetate and most other organic solvents

ICH Q3C residual solvent limit

Class 2; PDE 5.3 mg/day (530 ppm)

Chemically stable; it can slowly oxidise or hydrolyse (ring opening) under strongly acidic or basic conditions. It is hygroscopic. Store in an airtight container, protected from light, in a cool, dry place.

Incompatible with strong oxidising agents, strong acids and strong bases. It dissolves or swells many plastics and elastomers, so container and device materials must be chosen carefully.

Produced by reacting γ-butyrolactone with methylamine, followed by purification by distillation.

Irritant to skin, eyes and the respiratory tract and readily absorbed through the skin. It is classified in the EU as toxic to reproduction (category 1B) on the basis of developmental toxicity in animals, and its use in medicines requires justification of exposure.

Wear chemical-resistant gloves (for example butyl rubber), eye protection and protective clothing, and handle in a well-ventilated area or fume hood. Pregnant workers should avoid exposure.

A Class 2 residual solvent under ICH Q3C. Included in the FDA Inactive Ingredient Database (subcutaneous injections and periodontal products) and used in veterinary medicines in Europe.

2-Pyrrolidone; dimethylacetamide; dimethyl sulfoxide; povidone (its polymeric relative).

Because of its reproductive toxicity classification, alternative solvents should be considered first; where NMP is needed, the daily exposure should be kept within the ICH Q3C PDE unless otherwise justified.