Barentz. high-quality low nitrite excipients

Always a better solution

Nitrosamines are a class of chemical compounds formed when nitrites - which can be formed from nitrates - react with a secondary or tertiary amine. (1) many of which are classified as probable or known carcinogens (cancer-causing agents) in humans and known as N-nitrosamines, N-nitroso compounds, or NOCs. (2)

There are multiple reasons why nitrosamines can be present in drugs. According to the U.S. Food and Drug Administration (FDA), the presence of nitrosamines can arise from the drug's manufacturing process, its chemical structure, or even the conditions under which the drugs are stored or packaged. (3)

Recently, the FDA issued updated guidance for managing pharmaceutical nitrosamine impurities, introducing key changes to enhance safety and regulatory compliance. This guidance applies to any drug product that contains chemically synthesized active pharmaceutical ingredients (APIs) and is therefore at risk. (3)

In its position paper, "The Role of Excipients in Determining N-nitrosamine Risks for Drug Products," the IPEC Federation emphasized that the risk assessments by the drug product manufacturer should be designed to evaluate the potential sources of nitrosamine formation and contamination during the manufacturing of drug products and that the risk of the presence of nitrosamine compounds within excipients itself is very low; however, many excipients contain traces of nitrites that can result in formation of nitrosamines under specific conditions within the drug product. (4)

One critical strategy to regulate nitrosamine levels is the use of low-nitrite excipients. Manufacturers can significantly reduce the availability of precursors for nitrosamine formation by choosing excipients with low nitrite content. However, it can sometimes take work to find comprehensive information on nitrite levels for many groups of excipients.

Let's look at our comprehensive portfolio of low-nitrite excipients that provide the tools to innovate without compromise.

Selection of specific Low Nitrite Alternatives

 

a. Binders and Fillers: Lactose, mannitol, MCC and starch are the most common excipients used as binders and fillers. Notably, mannitol, available from reputable suppliers such as Roquette, serves as a filler and offers additional benefits concerning taste masking and moisture control. Also, when you use lactose as a filler, you can opt for a supplier such as MEGGLE, who have been monitoring nitrite content of Lactose regularly since many years. (5) The lowest amount of nitrite also in MEGGLEs direct compressible (DC) lactose grades (agglomerated, spray-dried, and anhydrous lactose) makes them a perfect solution to mitigate/reduce the risk of nitrosamine formation for drug product manufacturing. (5)

 

b. Disintegrants: Focusing on low nitrite grades of disintegrants is essential to ensure product safety and efficacy. Opt for well-sourced variants of crospovidone, sodium starch glycolate, and croscarmellose sodium. At Barentz, we prioritize sourcing ingredients from manufacturers committed to strategies for mitigating nitrosamines, particularly Roquette, to ensure the highest quality and safety standards in formulations.

 

c. Lubricants and Glidants: To improve the flow characteristics and manufacturability of formulations, it is important to use magnesium stearate sourced from well-controlled synthetic processes. This ensures consistency and helps prevent product contamination. Additionally, consider incorporating tribasic calcium phosphate glidants, such as those provided by Budenheim. These glidants not only enhance flow but also contribute to the overall stability of the final product.

 

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How can we help?

Selecting low nitrite excipients is one of the most effective approaches to reducing nitrosamine impurity formation.

At Barentz, we take pride in offering our customers high-quality low nitrite excipients. We work closely with companies that prioritize safety and quality in their ingredients.

Contact us today!

References:

(1) National Library of Medicine N-Nitrosamines,15th report in carcinogens (2021 Dec 21), From: NIH N-Nitrosamines:15Listings

(2) European Medicines Agency, Nitrosamine Impurities, From: https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/pharmacovigilance-post-authorisation/referral-procedures-human-medicines/nitrosamine-impurities.

(3) U.S Food & Drug Administration, Control of Nitrosamine Impurities in Human Drugs Guidance for Industry,  https://www.fda.gov/media/141720/download

(4) IPEC Federation, Position Paper. The Role of Excipients in Determining N-Nitrosamine Risks for Drug Products, (February 2024), From https://www.ipec-europe.org/uploads/publications/20240227-if-nitrosamines-position-paper-v2-f-1709022506.pdf

(5) MEGGLE, Risk Mitigation of Nitrosamines Formation in Drug Products paper, (March 2024). From: https://www.meggle-pharma.de/newsandexpertise/nitrosamines_role_of_excipients/

(6) Roquette, Navigating the Next Phase of Nitrosamine Compliance for Pharmaceutical Producers, https://www.roquette.com/pharma/nitrosamine-mitigation-low-nitrite-excipients?utm_source=linkedin&utm_medium=organic-social&utm_campaign=nitrosamine