3 years ago

Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA

Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA
Anders Lundqvist, David Dahlgren, Markus Sjöblom, Peter Langguth, Hans Lennernäs, Christer Tannergren, Erik Sjögren, Carl Roos
There is a renewed interest from the pharmaceutical field to develop oral formulations of compounds, such as peptides, oligonucleotides, and polar drugs. However, these often suffer from insufficient absorption across the intestinal mucosal barrier. One approach to circumvent this problem is the use of absorption modifying excipient(s) (AME). This study determined the absorption enhancing effect of four AMEs (sodium dodecyl sulfate, caprate, chitosan, N-acetylcysteine) on five model compounds in a rat jejunal perfusion model. The aim was to correlate the model compound absorption to the blood-to-lumen clearance of the mucosal marker for barrier integrity, 51Cr-EDTA. Sodium dodecyl sulfate and chitosan increased the absorption of the low permeation compounds but had no effect on the high permeation compound, ketoprofen. Caprate and N-acetylcysteine did not affect the absorption of any of the model compounds. The increase in absorption of the model compounds was highly correlated to an increased blood-to-lumen clearance of 51Cr-EDTA, independent of the AME. Thus, 51Cr-EDTA could be used as a general, sensitive, and validated marker molecule for absorption enhancement when developing novel formulations.

Publisher URL: http://dx.doi.org/10.1021/acs.molpharmaceut.7b00353

DOI: 10.1021/acs.molpharmaceut.7b00353

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.