What do you think of making a list of excipints brands that are offered as low-nitrite grade?
for example
I think we can start with fillers as are confirmed to be the largest source of nitrite in the drug products, for example:
*Microcrystalline celloluse
*Crosscarmellose sodium
Also DFE Pharma excipients are very low in nitrites:
Moreover, in our experience, also JRS MCC (Vivapur 101 and 102) have a low content of nitrites (<0.2%), even if they didn’t create a specific brand or published their data.
Thanks for sharing DFE white paper.
Unfortunately, we should not rely completely on the risk assessment delivered by the suppliers on taking our decisions. When we made our analysis, we have found significant nitrite content although the risk assessment received from the excipient supplier claims its absence!
It is necessary to distinguish between companies who have expressly reduced nitrite levels because they have found a root cause and corrected it and companies who may have low nitrite levels but don’t know why. Such materials may be at risk unless they undertake testing for every batch. I also have a suspicion that at least one company is cherry picking - that is they are analysing every batch and those below a certain level they sell at a low nitrite premium.
We still have a long way to go and one question which is rarely asked, is there a difference between nitrite levels and available nitrite. For example magnesium stearate always seems to have a very high nitrite level (ppm’s) but I have not seen it identified as a root cause so I wonder if the lipophilicity of the substance actually does not allow nitrite release during normal tabletting processes or on storage.
I think in the magnesium stearate case, its relative contribution to the final nitrite concentration in a product formula is low because of its usual low usage concentration unlike the fillers.
Caution when applying this type of reasoning. We must not forget the manufacturing process, because an excipient may be in low amount in the formulation, but if it has high nitrite contant and comes in contact with the amine source prior to the “dilution”, it may lead to nitrosamine formation at higher levels than expected
You may be right but we have seen figures upwards of 6,000 ppb so maybe with 1% MgSt you could have 60ppb. Not enough to be a problem in itself but maybe pushing the total nitrite (from other excipients) just over the level. I agree that it is an unlikely occurrence, not as a root cause but as a contributing factor.
MgStearate is always added as the very last step (most diluted) in the tabletting process so the only think that might come after would be film coating.
Dear all,
We would like to have your feedback on the following:
1-Do you know any maize starch, lactose, talc and copovidone manufacturing companies that are working to supply these materials (individually) with very low nitrite levels? We know some brands that assure that but only in combination formulas.
2-Do you know some labs that are offering nitrite quantification service using methods with lower LOD (<0.1-0.2 ppm)?
This is important since we are trynig to reduce nitrite content on our medice products. Feel free to share your thoughts on this.
Appreciate your help.
Thanks
Lactose should not be a problem - most lactoses have very low nitrite levels.