N-Nitrosodimethylamine formation in metformin hydrochloride sustained-release tablets: Effects of metformin and hypromellose used in drug product formulation

Article Pharmacology & Pharmacy

Avoiding N-nitrosodimethylamine formation in metformin pharmaceuticals by limiting dimethylamine and nitrite

Joerg Schlingemann et al.

Summary: This study found that Metformin API is not a significant source of NDMA in Metformin pharmaceuticals, and that NDMA is primarily created during the drug product manufacturing process involving heat and nitrite. Reduction of nitrite in excipients and limiting residual dimethylamine in API were effective means to reduce NDMA in the drug product. Furthermore, although NDMA may increase during storage, it does not reach levels that limit the shelf-life of the products under study.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2022)

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Article Chemistry, Analytical

N-Nitrosation in the absence of nitrosating agents in pharmaceuticals?

Jakub Jires et al.

Summary: The possibility of N-nitrosation in the absence of nitrosating agents was studied on model solutions and film coated tablets containing metformin. Alternative routes to N-nitrosation were found, where dimethylamine can undergo oxidation to nitrite in the presence of strong oxidants, followed by the nitrite acting as a nitrosating agent. The described reaction took place in both model solutions and tablets, but to a small degree in the tablets. Adjusting the pH of the solid dosage forms remains an effective measure of controlling N-nitrosamines in the product.

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS (2022)

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Article Chemistry, Analytical

Insight into the formation of N-nitrosodimethylamine in metformin products

Jakub Jires et al.

Summary: An effective analytical method for quantification of NDMA using liquid chromatography coupled with tandem mass spectrometry was developed and validated. Key factors behind NDMA formation were identified, and protective measures were proposed to prevent contamination in metformin products. Comparison between two laboratories confirmed the reliability of the method.

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS (2021)

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Article Chemistry, Medicinal

Inhibition of N-Nitrosamine Formation in Drug Products: A Model Study

Kausik K. Nanda et al.

Summary: The inhibition of nitrosamine formation in oral solid dosage forms is feasible with suitable inhibitors, as demonstrated for the first time in this study. Nitrosamine formation in drug products is possible when nitrite and vulnerable amines are present, highlighting the need for regulatory scrutiny and assessment. This research also suggests the potential use of amino acids as inhibitors of nitrosamine formation in solution.

JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

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Article Chemistry, Applied