Nitrosamine Prevention in the Granulation Process of Pharmaceuticals

ー Continuous Monitoring Trace-level Gas Concentration ー 

HORIBA's highly accurate trace gas analyzers can continuously monitor N compounds (NO, NO₂, N₂O etc.) to help clarify the cause of nitrosamine formation during the formulation granulation process.

Recently, nitrosamines, which are likely carcinogenic to humans, have been detected globally in the Sartan class of drugs, Ranitidine and Nizatidine. Medicines regulatory authorities, including the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Japanese Ministry of Health and Welfare (MHLW), have issued notices and guidance to pharmaceutical manufacturers and distributors, requesting self-inspection and assessment regarding the risk of nitrosamine contamination. The mechanism of nitrosamine formation is still under research, but one hypothesis suggests atmospheric N compounds could cause nitrosamine formation when ambient air is heated and used for drying formulation during the granulation process.

• Want to identify causative substance (NO, NO₂, N₂O etc.)
• Want to monitor the concentration of various impurities at inlet and outlet of fluidized bed granulation dryer
• Want to measure the impurity concentration in ppb level