Physiologically Based Pharmacokinetic (Pbpk) Oral Absorption Model To Predict Mucosal Permeability of Oral Cavity Drug Products

Authors: Kalra P, Le Merdy M, Lukacova V, Dwivedi P, Alam K, Tsakalozou E, Al-Ghabeish M, Pauletti GM, Zhou H
Conference: AAPS
Keywords: AAPS2023, drug products, gastroplus, in vitro in vivo relationship, membraneplus, oral absorption, PBPK modeling
Software: GastroPlus®, MembranePlus™
Division: Simulations Plus

Purpose

  • Buccal delivery allows bypassing first-pass metabolism
  • Evaluating buccal mucosal permeability is necessary to assess the pharmacokinetics (PK) of active pharmaceutical ingredients (APIs) intraorally delivered using mechanistic in silico approaches
  • In vitro permeability assays were conducted using the organotypic EpiOral™ tissue model  (ORL-200, MatTek Corp., Ashland, MA) (cf. Poster #T1030-04-26)
  • A mechanistic in silico model of the EpiOral™ tissue was developed and validated in MembranePlus™ software (beta version, Simulations Plus Inc., Lancaster, CA)
  • Diffusivity (Dm) and fraction unbound (fut) in the oral mucosa of the EpiOral™ tissue were determined for 8 APIs.

By Priyata Kalra, Maxime Le Merdy, Viera Lukacova, Pankaj Dwivedi, Khondoker Alam, Eleftheria Tsakalozou, Manar Al-Ghabeish, Giovanni Pauletti2, Haiying Zhou

AAPS 2023 PharmSci 360,Orlando, FL, October 22-25, 2023