I would like to hear your thoughts and ways of working when it comes to nitrosamines testing in finished products that consist of hard gelatin capsules.
I am aware of the EfPIA position regarding the fact that capsules are considered to be a negligible risk / source of reactive nitrites when we are working with oral solid dosage forms as the nitrites are immobilized in the gelatin however I would be curious to hear about your testing strategy and related argumentation when it comes to testing.
i) Do you dissolve the complete capsule as part of your confirmatory testing strategy or do you only test the capsule content (considering of course rinsing the capsule with an appropriate solvent to ensure that we extract the nitrosamine(s) if present)?
ii) Is the same approach followed for both the API related compounds and the low molecular weight nitrosamines?
iii) If the capsule is dissolved what is the approach to avoid the risk of false positive with potential reaction from the moment we will release the nitrites in solution. In some cases, simple pH correction is not possible as the drug could actually degrade to increase the level of secondary amine and the risk cannot be kept to a minimum.
Any input is valued!