Bioequivalence and Bioavailability Forum

Dear Amr,

if I understood you correctly you were asking how to avoid a bioequivalence study? A biowaiver cannot be granted for combination products - therefore I'm afraid you have to perform an in vivo BE study.

❝ [...] as there is no clear available data on pharmacokinetics for both

❝ active substances...

No?

• chlordiazepoxide: t½ 5 - 30 hours (t½ major active metabolite desmethyldiazepam 36 - 300 h (!); minor: temazepam 8 - 20 h, oxazepam 4 - 14 h)
  
• clidinium: t½ ≈20 hours (caution: unreliable data)

❝ [...] what is the most suitable design for this study.

Cross-over, single dose fasting, BE of both parent compounds. If you regulation allows truncated AUC₇₂, fine. Washout based on t½ of chlordiazepoxide.