Bioequivalence and Bioavailability Forum

Thank you Steven and Helmult. In my opnion you are the best experts at the moment.

I agree that caffeine has a behavior like BCS class 1. But, until the moment, I do not understand the reason of FDA does not request an option to waiver of in-vivo testing of this product according the Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence for Immediate – Release Solid Oral Dosage Forms Based on the Biopharmaceutics Classification System. Instead of this, FDA takes on that caffeine must not be measurable in bioequivalence studies as you can see in recommendations below:


Acetaminophen+ Aspirin+Caffeine
Acetaminophen+Butalbital+ Caffeine

Note in this guidance: Acetaminophen; Butalbital; Caffeine Capsules are a DESI1 effective drug for which there are no known or suspected bioequivalence problems, and as such is rated “AA” in the FDA/CDER’s Approved Drug Products with Therapeutic Equivalence Evaluations (“Orange Book”).

Acetaminophen+Butalbital+ Caffeine+ Codeine phosphate