Surface Activity Profiling (SAP): A potential means of predicting intestinal membrane permeability

Eur J Pharm Biopharm. 2019 Sep:142:291-299. doi: 10.1016/j.ejpb.2019.06.024. Epub 2019 Jun 20.

Abstract

Early characterization of new drug substances intended for oral application includes not only physicochemical properties and stability but also the ability of the substance to permeate through the intestinal mucosa. In this work, a rapid screening method, surface activity profiling (SAP), is proposed as an alternative to animal studies and screening in cell cultures. Measurements are made with a multichannel tensiometer and require only 50 µl of stock solution for the complete permeability analysis. Correlation of SAP results with human absorption was demonstrated for marketed drugs and with absorption in rats for development compounds of Boehringer Ingelheim. Cross-laboratory results for marketed drugs showed excellent agreement. For early stage investigations of lead compounds, where only small amounts of the compound are available, the SAP method appears to be an effective and fast tool to accurately predict fa, provided the compound is amphiphilic.

Keywords: Oral drug absorption; PAMPA; Permeability; Surface activity analysis; Tensiometer.

MeSH terms

  • Animals
  • Cell Membrane Permeability / physiology*
  • Female
  • Humans
  • Intestinal Absorption / physiology*
  • Intestinal Mucosa / metabolism*
  • Male
  • Membranes, Artificial
  • Rats
  • Rats, Wistar

Substances

  • Membranes, Artificial