MEGGLE White Paper: Excipient roles in mitigating nitrosamine formation in drugs

Pharmaceutical lactose specialist MEGGLE has released a technical White Paper on the risks of nitrosamine contamination of drug products and the role that excipient choices can play in reducing them.

The White Paper Risk Mitigation of Nitrosamines Formation in Drug Products is authored by MEGGLE Head of R&D,  Ricarda Leister and is available for free download from MEGGLE.

Nitrite factors

The White Paper provides an overview of reasons for increasing industry concern about the issue of Nitrosamine impurities in drug and excipient manufacturing, with unacceptable amounts of N-nitrosodimethylamine (NDMA) found in several medications.

Among other things, the paper discusses:

• Potential sources of nitrites in excipients
• The real meaning of the term ‘nitrite free’
• Appropriate limits for nitrites and challenges in trace methods
• The importance of assessing potential matrix effects (co-elution)in the intended analytical methods for nitritre determination The measures MEGGLE has adopted to ensure very low nitrite level inits products

Industry strategies

Leister proposes a number of strategies for mitigating nitrosmaine risks in drug product manufacturing with reference to useful recent research and current regulatory guidelines.

She also provides guidance on suitable analytical mehods and the associated draw backs, namely the sensitivitiy (limit of detection) of the available methods as as well as the risk of co-eluation for example in Ion chromatography combined wit UV/Vis detection

She concludes that the key factors are careful selection of API and excipients in terms of type and amounts uses, together with the API manufacturing process and potential impurities or precursors, along with the drug product manufacturing process itself, and advantages of reformulating products to adopt direct compression that  avoids the use of water and heat.