Excipient Selection Strategies to Mitigate Nitrosamine Risks
Author(s): Joseph Zeleznik, Sydney Badger, Manish Ghimire
This is an article from PHARM TECH.
Key Takeaways
- Nitrosamines arise via nitrosating agents (nitrites, NO2/NOx, nitrous acids/oxides) reacting with secondary/tertiary amines or some amides, yielding high-risk N-nitroso compounds.
- Regulatory actions after valsartan, broader sartans, ranitidine, and metformin triggered global acceptable-intake limits (~26.6–1500 ng/day) and expectations for lifecycle control across administration routes.
- Excipient suppliers are quantifying and reducing nitrosating agents; nitrogen-free mannitol and low-nitrite microcrystalline cellulose exemplify material choices that mitigate formation without compromising compaction performance.
- Manufacturing process choices influence risk: wet granulation, elevated temperature/humidity, and recycled solvents can amplify nitrosamine formation, whereas direct compression or dry granulation/roller compaction reduce triggering conditions.
- Risk evaluation follows EMA/FDA frameworks for identification, quantitation, and mitigation, supported by IPEC’s standardized excipient questionnaire and screening of scavengers (eg, lysine, cysteine, ascorbate) for product-specific efficacy.
https://www.pharmtech.com/view/excipient-selection-strategies-to-mitigate-nitrosamine-risks