Investigation of drug partition kinetics to fat in simulated fed state gastric conditions based on drug properties

Fotios Baxevanis, Panagiota Zarmpi, Jesse Kuiper, Nikoletta Fotaki

Research output: Contribution to journalArticle

Abstract

The presence of fat in the gastric environment can affect the pharmacokinetic behaviour of drugs with mechanisms which have not been yet fully understood. The objective of the current study was to assess the drug partition to the lipid part of the fed gastric content under different emulsification conditions, using in vitro discriminating setups. The model drugs used in the study were selected on the basis of different physicochemical properties (lipophilicity, ionization, molecular weight and aqueous solubility) and different food effect observed in in vivo human studies. Fed State Simulated Gastric Fluid prepared with skimmed milk (FeSSGF sk) and anhydrous milk fat were used as surrogates for the aqueous and fat portions of the fed gastric environment respectively. An optimized biphasic model was developed so as to predict the differences in partition rate constants to fat, for model drugs of a wide range of the properties mentioned above. The experimental data and the use of statistical analysis revealed that molecular weight, molecular weight and log D pH 5 interaction and negative food effect act as negative factors to the rate constants of fat partition, while absence of food effect and logD pH 5 interaction with aqueous solubility affect the rate constants of partition to fat favourably.

Original languageEnglish
Article number105263
JournalEuropean Journal of Pharmaceutical Sciences
Volume146
Early online date12 Feb 2020
DOIs
Publication statusPublished - 15 Apr 2020

Keywords

  • Drug partition
  • Fed state
  • Food effect
  • Partial least squares regression
  • Physicochemical properties

ASJC Scopus subject areas

  • Pharmaceutical Science

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