Bioequivalence and Bioavailability Forum

Hi Bloom,

❝ For highly soluble-low permeable drugs, the rate of drug absorption is limited by permeability which is also governed by gastric emptying time (or availability of drug at the site of absorption). For any highly soluble if drug release >85% in 20-30 min, then only absorption would be mainly controlled by the emptying from the stomach(normal GIT: 10-120 min depending upon the type of phase).

Bingo!

❝ In your case where the reference is releasing no less than 80% at 30 mins, and your product is releasing no less than 80% at 60 mins; I would be a bit cautious as it would surely affect the rate of drug availability at the site of absorption and your formulation is some how controlling the rate of release. BTW you mentioned Tmax=8 hrs, is there any lag time or the plasma concentration picks up slowly?

No lagtime and both T and R have 7.6 - 8 hr Tmax.
My question to the formulators was that if the product leaves the stomach at less than 60 mins, and if you want a spec of >=80 at 60 mins, I see a potential problem of the remaining part of the product not dissolving at post gastric pH, which can affect PK. The knucklehead director wouldn't listen and insisted that there shouldn't be any effect on BE because the Tmax is so long because drug permeability is the rate limiting step in our case.

❝ Any information about behaviour in fed condition?

No different. No food effect on Tmax.

Thanks
John