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Pharmaceutical Research

, 35:55 | Cite as

Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption

  • Mirko Koziolek
  • Frédéric Carrière
  • Christopher J. H. Porter
Expert Review

Abstract

Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to ‘pre-process’ lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.

KEY WORDS

Biorelevant dissolution Food effect Gastric lipolysis Human gastric lipase In vitro digestion Lipids Milk 

Abbreviations

AUC

Area under the curve

CCK

Cholecystokinin

DAG

Diacylglycerol

DGL

Dog Gastric Lipase

EMA

European Medicines Agency

FDA

United States Food and Drug Administration

FFA

Free Fatty acid

HGF

Human Gastric Fluid

HGL

Human Gastric Lipase

LBF

Lipid Based Formulations

LCFA

Long chain fatty acid

LCT

Long chain triacylglycerol

LFCS

Lipid Formulation Classification System

MAG

Monoacylglycerol

MCFA

Medium chain fatty acid

MCT

Medium chain triacylglycerol

MRI

Magnetic resonance imaging

PEI

Pancreatic exocrine insufficiency

PWSD

Poorly water-soluble drugs

rDGL

Recombinant Dog Gastric Lipase

RGE

Rabbit Gastric Extract

SGF

Simulated Gastric Fluid

TAG

Triacylglycerol

SCFA

Short chain fatty acid

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by a fellowship within the Postdoc-Program of the German Academic Exchange Service (DAAD).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mirko Koziolek
    • 1
    • 2
  • Frédéric Carrière
    • 3
  • Christopher J. H. Porter
    • 2
    • 4
  1. 1.Department of Biopharmacy and Pharmaceutical Technology, Center of Drug Absorption and TransportUniversity of Greifswald, GermanyGreifswaldGermany
  2. 2.Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia
  3. 3.Aix-Marseille Université, CNRS, UMR 7282 Enzymologie Interfaciale et de Physiologie de la LipolyseMarseille Cedex 20France
  4. 4.ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia

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