The Effect of Food on the Oral Bioavailability of Drugs: a Review of Current Developments and Pharmaceutical Technologies for Pharmacokinetic Control

Abstract

Here we review the mediation of the food effects on drugs by pharmaceutical technologies. The pharmacokinetics of drugs are affected by the interaction of drugs with food, which changes drug physicochemical and physiological properties (food effects). Several pharmaceutical technologies may be used to control food effects. Drugs exhibit different patterns of solubilization depending on release formulations. Formulations such as nanoparticle, solid dispersion and cyclodextrin systems, may control the solubility and release of insoluble drugs. Other controlled-release technologies, such as osmotic-controlled release or colon-specific delivery systems may also control food effects. As the structure of drug candidates becomes more complex, different methods of investigation, such as in vitro and in vivo correlation and in silico simulation will be required to predict drug characteristics and food effects.

Statistical investigation of simulated fed intestinal media composition on the equilibrium solubility of oral drugs

“…It is appreciated therefore that the dynamic and complex physiology of the gastrointestinal tract influences drug absorption ( Varum et al, 2013 ). Two major features of the gut are the inherent physicochemical conditions within the tract which vary with position along the tract ( Bergstrom et al, 2014 , Mudie et al, 2010 ) and the effect of ingested food ( Yasuji et al, 2012 ) on these conditions, both of which exhibit intra- and inter-subject variability. Simple aqueous drug solubility therefore cannot reflect gastrointestinal solubility ( Dressman et al, 2007 ) and in order to improve this determination in vitro, either sampled human fluids can be employed ( Augustijns et al, 2014 ) or simulated gastrointestinal media prepared ( Vertzoni et al, 2004 ).…”

Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants

“…In addition, food-drug interaction may affect drug clearance and metabolism through changes in the splanchnic blood flow and plasma protein binding and modulation of drug-metabolizing enzymes [22,23]. Therefore, it is important to establish the impact of food on the oral bioavailability and PK of the canagliflozin/ metformin IR FDC tablet in order to understand the clinical relevance of food-induced changes on both canagliflozin and metformin efficacy and tolerability and determine optimum timing of drug administration relative to meal times.…”

Enabling an HCV Treatment Revolution and the Frontiers of Solid Solution Formulation

“…28 Formulation approaches are commonly used to lessen or eliminate positive food effects. 29 However, addressing a negative food effect via formulation approaches is far less common.…”