Functional Category
Penetration agent; plasticizer; solvent; solubilizing agent.
Applications in Pharmaceutical Formulation
Pyrrolidone and N-methylpyrrolidone (see Section 17) are mainly used as solvents in veterinary injections. Pyrrolidone has been shown to be a better solubilizer than glycerin, propylene glycol, or ethanol.(1) They have also been suggested for use in human pharmaceutical formulations as solvents in parenteral, oral, and topical applications. In topical applications, pyrrolidones appear to be effective penetration enhancers.(2–6) Pyrrolidones have also been investigated for their application in controlled-release depot formulations.(4,7)
Description
Pyrrolidone occurs as a colorless or slightly grayish liquid, as white or almost white crystals, or colorless crystal needles. It has a characteristic odor
Stability and Storage Conditions
Pyrrolidone is chemically stable and, if it is kept in unopened original containers, the shelf-life is approximately one year. Pyrrolidone should be stored in a well-closed container protected from light and oxidation, at temperatures below 208C.
Incompatibilities
Pyrrolidone is incompatible with oxidizing agents and strong acids.
Safety
Pyrrolidones are mainly used in veterinary injections and have also been suggested for use in human oral, topical, and parenteral pharmaceutical formulations. In mammalian species, pyrrolidones are biotransformed to polar metabolites that are excreted via the urine.(8,9) Pyrrolidone is mildly toxic by ingestion and subcutaneous routes; mutagenicity data have been reported.(10) LD50 (guinea pig, oral): 6.5 g/kg(10) LD50 (rat, oral): 6.5 g/kg