Bioequivalence and Bioavailability Forum

Dear Kaushik!

❝ My question is when we are administering a dose which is a tablet that has to be taken with some applicable amount of drinking water then what if the subject chewed the tablet instead of swallowing it?

The protocol should state how the formulations are administered. The protocol should refer to posology given in the label/SmPC of the reference and the IMPD/IB of the test product. If nothing specific is given I would assume the worst case “must be swallowed unchewed as a whole”.

❝ will it impact the Pk parameters?

Even if nothing specific is stated in the label/SmPC and/or IMPD/IB you should not assume that absorption will not be influenced. Expect are more pronounced effect for all types of MR products. For delayed release you can expect serious dose dumping (product behaves like an IR formulation) or very low / no concentrations at all if the API is susceptible to degradation in the acidic environment of the stomach. For CR you can expect faster absorption – though not necessarily complete dose dumping.

❝ Can we continue the subject in the study or not??

Given the above (and assuming you have stated nothing in the protocol) I would write an amendment or at least a note to file stating that the subject will be taken out from the confirmatory assessment of bioequivalence. You can present the complete data set (with the subject) in an exploratory manner. Personally I would assume the worst case scenario and take the subject out (no further dosing, but samples analyzed).