Rate- and Extent-Limiting Factors of Oral Drug Absorption: Theory and Applications

ABSTRACTThe oral absorption of drugs has been represented by various concepts such as the absorption potential, the maximum absorbable dose, the biopharmaceutics classification system, and in vitro–in vivo correlation. The aim of this article is to provide an overview of the theoretical relationships between these concepts. It shows how a simple analytical solution for the fraction of a dose absorbed (Fa equation) can offer a theoretical base to tie together the various concepts, and discusses how this solution relates to the rate-limiting cases of oral drug absorption. The article introduces the Fa classification system as a framework in which all the above concepts were included, and discusses its applications for food effect prediction, active pharmaceutical ingredient form selection, formulation design, and biowaiver strategy. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.