Nitrosamine mitigation: NDMA impurity formation and its inhibition in metformin hydrochloride tablets -Pub FDA

A new paper was published yesterday.

Nitrosamine mitigation: NDMA impurity formation and its inhibition in metformin hydrochloride tablets - ScienceDirect

I have only very quickly skim read, and while it is nice from a confirmation of principle perspective I think there are some issues with it.

The continued work on caffeic acid and ferulic acid, because the FDA mentioned them a lot at the beginning, means work is going on using materials that are not approved excipients, and bring their own problems. The same with BHA/BHT - both of which have their own safety concerns.

It looks like samples were spiked at 500ppm nitrite, which is far in excess of any levels of nitrite that should be present in finished products, and therefore means that much higher levels of scavenger have been added that would potentially be required if there were, say, 5ppm of nitrite in the finished product. It means levels of 1% of scavenger are talked about, when the reality may be that much lower levels are the reality (and possibly negate the requirement for bioequivalence testing).

As I said, I have only quickly read before a meeting, so happy to discuss if people have other take-outs from it.

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@MarkS, Dr. Shakleya will present the research’s outcome at the upcoming FDA-CRCG workshop. Stay tuned!

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Thank you for sharing the information, @MarkS. Although the addition of sodium nitrite seems to be 100 ppm, it is still too much. The investigation includes lots of information and I need to read it a few more times to understand.