Bioequivalence and Bioavailability Forum

Hi Sukalpa,

❝ ❝ Reformulate.

❝

❝ OK. I would like to mention one thing that, the failed study was fed one, fasting study passed quite comfortably (both ABE and SABE). Is there any possibility that the test formulation is more variable in fed condition?

That’s quite possible. An extreme example of the past: The first PPIs were monolithic gastric-resistant formulations. Crazy variability, both fasting and fed. Current formulations are capsules with gastric-resistant pellets. Variability still high but way better than the monolithic forms. Of course, when the capsules were introduced, BE studies were performed. All PK metrics passed but by inspecting the profiles you could clearly see the lower variability of the capsules. OK, these are easy drugs (now many are already OTCs). Imagine that they would be NTIDs and the formulation change the other way ‘round (capsule → monolithic). No way ever to pass the s_wT/s_wR criterion.

In your case this means again to reformulate. Don’t ask me how (I’m not a formulation chemist). Maybe dissolution testing in the various stinking FeSSIF “biorelevant” media helps.

❝ This is the first time I am posting something in this forum. Bit confused regarding the rules and regulation of this forum.

Some hints in the Policy.