Food for thought: formulating away the food effect - a PEARRL review

Abstract

Objectives: Co‐ingestion of oral dosage forms with meals can cause substantial changes in bioavailability relative to the fasted state. Food‐mediated effects on bioavailability can have significant consequences in drug development, regulatory and clinical settings. To date, the primary focus of research has focused on the ability to mechanistically understand the causes and predict the occurrence of these effects. Key findings: The current review describes the mechanisms underpinning the occurrence of food effects, sheds new insights on the relative frequency for newly licensed medicines and describes the various methods by which they can be overcome. Analysis of oral medicines licensed by either the EMA or FDA since 2010 revealed that over 40% display significant food effects. Due to altered bioavailability, these medicines are often required to be dosed, rather restrictively, in either the fed or the fasted state, which can hinder clinical usefulness. Summary: There are clinical and commercial advantages to predicting the presence of food effects early in the drug development process, in order to mitigate this risk of variable food effect bioavailability. Formulation approaches aimed at reducing variable food‐dependent bioavailability, through the use of bio‐enabling formulations, are an essential tool in addressing this challenge and the latest state of the art in this field are summarised here.