An Investigation into the Importance of "Very Rapid Dissolution" Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology

Abstract

The Biopharmaceutics Classification System (BCS) is based on the mechanistic assumptions that the rate and extent of oral drug absorption are governed by drug solubility, intestinal permeability, and dissolution rate from the dosage form administered. One of the goals of BCS is to identify classes of drugs for which bioequivalence may be established based solely on the in vitro dissolution data, i.e., which would be eligible for biowaiver. On the basis of BCS, currently, the biowaiver concept is adopted and recommended for immediate release of drug products containing highly soluble and highly permeable compounds (BCS class 1 drugs). Dissolution testing properties are proposed to be more stringent: very rapid dissolution is demanded when generic drug application is submitted with the exemption of in vivo bioequivalence study. In the present paper, Gastrointestinal Simulation Technology has been applied in order to evaluate the potential for different in vitro drug dissolution kinetics to influence dosage forms in vivo behavior and the relevance of "very rapid dissolution" criteria to be met (i.e., more than 85% of dose dissolved in 15 min).