Bioequivalence and Bioavailability Forum

Dear Ken!

❝ The test tablet contains Chlorzoxazone 250mg and Paracetamol 300mg. The reference tablet contains only Chlorzoxazone 200mg.

I don’t know the Malaysian requirements for FDCs. In many regulations you have to provide a clinical justification. As a starter I recommend EMA’s guideline.

❝ What is the best way to run BE study ? Can we ignore the presence of paracetamol ?

No, you can’t. Even if you find literature data demonstrating lack of PK interaction between the two APIs you cannot exclude it for the reference formulations (excipients,…). The GL calls for demonstrating BE in a 2×2 cross-over study with “the free combination of the recognised reference formulations of the individual monocomponents and the marketing formulation (fixed combination)” – of course at the same dosages.

❝ Give 4 tablets of test and 5 tablets of reference to make sure the dose is equal.

Theoretically, yes. But you would have to include 1200 mg of paracetamol in the reference arm as well – which is a quite high single dose (maximum daily dose 4000 mg). 1000 mg of chlorzoxazone is far above the maximum daily dose of 650 mg. I don’t see how one could justify such a study.