Affordable Access

deepdyve-link
Publisher Website

In-vitro-in-silico investigation of the negative food effect of zolpidem when administered as immediate-release tablets.

Authors
  • Paraiso, Rafael Leal Monteiro1
  • Watanabe, Ayahisa2
  • Andreas, Cord J1
  • Turner, David3
  • Zane, Patricia4
  • Dressman, Jennifer1
  • 1 Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. , (Germany)
  • 2 Research Laboratory for Development, Shionogi & Co., Ltd., Osaka, Japan. , (Japan)
  • 3 Simcyp Division, Certara UK Limited, Sheffield, UK.
  • 4 Drug Disposition, Safety, and Animal Research (DSAR), Sanofi U.S., Bridgewater, NJ, USA.
Type
Published Article
Journal
The Journal of pharmacy and pharmacology
Publication Date
Nov 01, 2019
Volume
71
Issue
11
Pages
1663–1676
Identifiers
DOI: 10.1111/jphp.13161
PMID: 31566757
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The main objective of the present work was to combine in-vitro and in-silico tools to better understand the in-vivo behavior of the immediate release (IR) formulation of zolpidem in the fasted and fed states. The dissolution of zolpidem was evaluated using biorelevant media simulating the gastric and intestinal environment in the fasted and fed states. Additionally, the influence of high viscosity and high fat content on the release of zolpidem under fed state conditions was investigated. The in-vitro results were combined with a physiologically based pharmacokinetic (PBPK) model constructed with Simcyp® to simulate the zolpidem pharmacokinetic profile in both prandial states. In vitro biorelevant dissolution experiments representing the fasted and fed states, combinedwith PBPKmodelling, were able to simulate the plasma profiles from the clinical food effect studies well. Experiments reflecting the pH and fat content of themeal led to a good prediction of the zolpidem plasma profile in the fed state, whereas increasing the viscosity of the gastricmedia led to an under-prediction. This work demonstrates that the combination of biorelevant dissolution testing and PBPK modelling is very useful for understanding the in-vivo behavior of zolpidem in the fasted and fed states. This approach could be implemented in the development of other drugs exhibiting negative food effects, saving resources and bringing new drug products to the market faster. © 2019 Royal Pharmaceutical Society.

Report this publication

Statistics

Seen <100 times