Fed state: T higher variable than R [Study Assessment]
Hi Sukalpa,
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 swT/swR 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.
Some hints in the Policy.
❝ ❝ 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 swT/swR 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.
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- NTI drug Bioequivalence study Statistical approach Sukalpa Biswas 2019-08-06 09:15 [Study Assessment]
- Cherry-picking? Helmut 2019-08-07 11:09
- digging out the possible reasons of the failure Sukalpa Biswas 2019-08-09 06:11
- Fed state: T higher variable than RHelmut 2019-08-09 12:36
- digging out the possible reasons of the failure Sukalpa Biswas 2019-08-09 06:11
- Cherry-picking? Helmut 2019-08-07 11:09