Dear both,
theoretically every suggestion is right, but from a practical point of view, in my opinion you shoot flies with a gun.
- Acidic Conditions: When povidone is dissolved in water, the resulting solution can have a pH between 3.5–5, depending on the concentration. OK, right.
2. Amine Source
Generally, amides can be hydrolyzed in either acidic or basic solution. The mechanisms are much like those of ester hydrolysis, but the reactions are very much slower. Hydrolysis under acidic conditions requires strong acids such as sulfuric or hydrochloric, and temperatures of about 100°C for several hours. In alkaline hydrolysis the amide is heated with boiling aqueous sodium or potassium hydroxide.
Hydrolysis of Amides
3. Nitrosating Agents: I do not know your local requirement for Purified Pharmaceutcal water, but according to Ph.Eur monograph nitrates (and consequently nitrites) should be practically absent (maximum 0.2 ppm).
Morover, “If purified water in bulk complies with the requirements for conductivity prescribed for Water for injections (0169) in bulk, it is not necessary to carry out the test for nitrates prescribed above.”
Summarizing, in my opinion the possible formation of nitrosamines during the granulation is negligible respect to the possible increase during the shelf-life due to nitrite impurities in critical excipients.
See also the following discussion:
4-(nitroso(vinyl)amino)butanoic acid from Kollidon?