Bioequivalence and Bioavailability Forum

❝ However, if bioequivalence between ODT taken without water and reference formulation with water is demonstrated in a 2-period study, bioequivalence of ODT taken with water can be assumed."

What about such a situation:
- ODT without water (w-) and IR with water (w+) have indeed the same bioavailability, as mentioned in the guidance:
(1) F_ODT|w- / F_IR|w+ = 1
- Taking ODT with water results in a biovailability decreased by 30%:
(2) F_ODT|w+ / F_ODT|w- = 0.7
- Then, the bioavailability of ODT with water relative to IR with water is:
F_ODT|w+ / F_IR|w+ = (1) x (2) = 0.7
=> ODT with water can certainly NOT be assumed bioequivalent to IR with water

The assumption (2) above does not seem unrealistic, as the rationale for developing an ODT alternative to an existing oral formulation could be to improve the bioavailability by increasing its absorption by the buccal mucosa and then limiting some acidic degradation in the stomach or a strong 1^st-pass effect.

So, either I miss completely the point somewhere, or the guidance actually does not care about BE with water... even if it tries to convince us of the opposite ???