Interaction of Commonly Used Oral Molecular Excipients with P-glycoprotein

AAPS J. 2021 Sep 15;23(5):106. doi: 10.1208/s12248-021-00631-8.


P-glycoprotein (P-gp) plays a critical role in drug oral bioavailability, and modulation of this transporter can alter the safety and/or efficacy profile of substrate drugs. Individual oral molecular excipients that inhibit P-gp function have been considered a mechanism for improving drug absorption, but a systematic evaluation of the interaction of excipients with P-gp is critical for informed selection of optimal formulations of proprietary and generic drug products. A library of 123 oral molecular excipients was screened for their ability to inhibit P-gp in two orthogonal cell-based assays. β-Cyclodextrin and light green SF yellowish were identified as modest inhibitors of P-gp with IC50 values of 168 μM (95% CI, 118-251 μM) and 204 μM (95% CI, 5.9-1745 μM), respectively. The lack of effect of most of the tested excipients on P-gp transport provides a wide selection of excipients for inclusion in oral formulations with minimal risk of influencing the oral bioavailability of P-gp substrates.

Keywords: P-glycoprotein; calcein-AM assay; digoxin flux; oral excipients; screening assays.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Administration, Oral
  • Excipients / administration & dosage
  • Excipients / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Lissamine Green Dyes / administration & dosage
  • Lissamine Green Dyes / pharmacology
  • beta-Cyclodextrins / administration & dosage
  • beta-Cyclodextrins / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Excipients
  • Lissamine Green Dyes
  • beta-Cyclodextrins
  • Light green SF
  • betadex