Evaluation of Biopharmaceutics Classification System Class 3 Drugs for Possible Biowaivers

The Biopharmaceutics Classification System (BCS) is employed by the US FDA to categorize drug substances into 4 classes and to characterize drugs in terms of aqueous solubility and intestinal permeability. The four BCS categories for a drug substance are Class 1, Class 2, Class 3, and Class 4. Biopharmaceutical properties of aqueous solubility and intestinal permeability with drug product dissolution determine the rate and extent of drug absorption from immediate-release (IR) and solid oral dosages forms (e.g. tablets,capsules). Each class exhibits information regarding biopharmaceutic properties and bioequivalence. For example, Class 1 drugs have the most favorable oral biopharmaceutic properties (high solubility and high permeability). With these biopharmaceutic properties for class 1 drugs, results in vivo bioequivalence (BE) studies for rapidly dissolving IR solid oral dosage forms the FDA provided waivers. This approach alone has resulted in new and generic drugs approved based on vitro data alone (i.e. biowaived), with great savings in resources and reduction in unnecessary human testing.

Objectives: 1) The primary objective of this study is to assess whether common excipients cause bioinequivalence of Class 3 drugs. 2) The secondary objective is the results of the study will contribute towards providing scientific evidence to the FDA for consideration of Class 3 drugs for BCS-based biowaivers.

Hypotheses: The investigators anticipate that common excipients do not cause bioinequivalence. 1) Hence, the hypothesize of this study is commonly used excipients in oral medications (tablets, capsules) modulate the rate or extent of Class 3 drug absorption and result in bioinequivalence. 2) Alternative hypothesis is that commonly used excipients in oral medications (tablets, capsules) do not modulate the rate or extent of Class 3 drug absorption and do not result in bioinequivalence.