Bioequivalence and Bioavailability Forum

Hey John

❝ Assume this scenario...

❝ Under the same dissolution medium, assuming the reference is releasing no less than 80% at 30 mins, and your product is releasing no less than 80% at 60 mins. What do you think?

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).

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?

If there is a lag of 1-2 hrs, may be the differences would not be that prominent but if there is no T lag, it might affect the absorption (saturation absorption?? Metabolism???)

Any information about behaviour in fed condition?
How the formulation behaviour in viscous media??? Any disintegration delays??


Try these papers, good read for BCS class III drug
a) Tsume, Yasuhiro; Amidon, Gordon L.; The Biowaiver Extension for BCS Class III Drugs: The Effect of Dissolution Rate on the Bioequivalence of BCS Class III Immediate-Release Drugs Predicted by Computer Simulation; Molecular Pharmaceutics; 7, 4, 1235-1243

For simulating Fed condition
b) Jelena Parojčić, Dragana Vasiljević, Svetlana Ibrić, Zorica Djurić; Tablet disintegration and drug dissolution in viscous media: Paracetamol IR tablets; International Journal of Pharmaceutics 355 (2008) 93–99