Resolving intraluminal drug and formulation behavior: Gastrointestinal concentration profiling in humans

Despite the wide use of the oral route to deliver systemic drugs to humans, the intestinal absorption process is still not fully understood. Especially for complex absorption-enabling strategies (e.g. solubilization, supersaturation, etc.), the in vivo performance is difficult to predict. Considering the current share of drug candidates that suffer from a non-favorable absorption potential and therefore rely on these strategies, there is a growing interest in approaches that aim to resolve the multitude of interactions between drugs, formulation factors and the gastrointestinal environment. In this respect, gastrointestinal concentration profiling following drug administration to humans is a recent but promising strategy that complements more established techniques including gastrointestinal imaging. In the present review, a number of case studies will be discussed to demonstrate the added value of gastrointestinal concentration profiling to gain in-depth knowledge of intraluminal drug and formulation behavior and to identify those processes key for drug absorption. Examples include a better understanding of intestinal precipitation of weakly basic drugs, clarifying inter-individual or food-induced variability in absorption, and an improved insight into the solubility-permeability interplay. As manifested in a recently initiated European project on oral biopharmaceutics tools (OrBiTo), intraluminal concentration profiling will contribute to the development of relevant simulation models that are built upon a solid understanding of human drug and formulation behavior, and allow for a more predictive in vitro and in silico evaluation of absorption.