GB2599950A — Pharmaceutical compositions with low amounts of nitrosamine impurities and methods for producing the same

USPTO Abstract

Pharmaceutical composition comprising an active pharmaceutical ingredient or salt thereof. The composition comprises less than 100 ppm peroxide impurities and more than 50 ppm amine impurity. The preferred API is metformin hydrochloride. Preferably the composition comprises a low peroxide grade excipient, especially povidone K25 or povidone LP30. The composition may comprise an anti-oxidant, free radical, scavenger, or reducing agent, especially sodium sulphite. The amine impurity may be dimethylamine. A pharmaceutical composition comprising an API and a pH modifying agent. The composition comprises more than 50 ppm peroxide impurities and less than 50 ppm amine impurity. The pH modifying agent may be a base, especially sodium carbonate or sodium bicarbonate. A method for reducing the amount of amine impurities in an API comprising crystallising the API from solution and removing the solvent. The solvent may be water, an alcohol, or mixtures thereof. A method for reducing the amount of amine impurities in an API comprising heating the API to a temperature of 50 – 120 oC. The compositions and methods of the invention reduce the amount of nitrosable compounds in the API and/or reduce the conversion of nitrosable compounds into nitrosamines in the finished dosage form.