Bioequivalence and Bioavailability Forum

Hi Tina,

❝ ❝ I would reformulate. BTW, what was the ratio for C_max?

❝

❝ 116 was the ratio for C_max.

OK, identical to AUC. So the behavior is according to the textbook.

❝ Reformulation for an IR product is quite tricky esp if Cmax is matching. This scenario is possible for MR product for which IVIVC will give a clear picture.

❝

❝ How would reformulation be planned for an IR product with matching Cmax but dissimilar AUC 0-t?

You have the same ratio for AUC and C_max, both pointing in the same direction – higher absorption. I would not call a C_max-ratio of 116% “matching”. Actually I don’t understand your problem. You have a better formulation. Now make it as bad as the reference.

What you have given so far: n 20
AUC upper CL 135%, ratio 116%, CV 24%.
C_max passing BE (so upper CL ≤125%), ratio 116%, CV 25%.
Your numbers don’t makes sense. If I assume the worst case for C_max (upper CL 125%) in order to get a ratio of 116%, the lower CL would have to be ~108%* – which gives for n 20 a CV of 13.7% – not the 25% you stated.
I don’t like this question and answer game. In the future please give all required information already in the first post (ratio, CI, CV%, sample size for all relevant PK metrics).

❝ Can IVIVC be done for IR product?

No. Makes only sense if disintegration/liberation/dissolution is the rate-limiting step.

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• 100×1.16²/1.25=107.648%