I will be delving into this a little more - I think the graphs are slightly misleading by including the “commercial product”.
I would also potentially question the use of the f2 testing where there are multiple values above 85% dissolved. @Naiffer_Host - something to discuss with Ken Broda, as to the suitability of the test. Even doing this, the values are only just above 50.
Thanks, @MarkS, for tagging me here. I will do my best to steer away from discussing the protocols/methods used and conclusions related to the dissolution results.
In our Nitrosamines multiverse, the issue of reformulating is beyond the dosage form in-vitro performance. The question we are after is: Does the reformulation change the efficacy of the medication? The most recent data published by FDA and the revised guidance mention: “FDA believes that immediate-release (IR) solid oral and oral suspension products (which are expected to behave similarly to solid oral IR products in terms of rapid dissolution and absorption through the gastrointestinal tract) incorporating an API that is BCS I, II, or III and reformulated to include one of the antioxidants evaluated by FDA or a pH modifier would not be expected to change in quality or clinical performance.”
For reference only: 1) A mechanically calibrated instrument does not comply with USP <711>, so the results cannot be considered USP compliant. 2) Peak-vessels or APEX vessels are not compendial, so results cannot be considered USP complaints. Swapping dissolution vessels to improve dissolution destroys the validation of the method and its discriminatory power. So it needs to be considered a whole new method that needs to be fully validated. The f2 comparison loses any effect once one forces the dissolution.
