Mechanistic in vitro Oral Absorption Model to Predict Mucosal Permeability of Oral Cavity Drug Products

Conference: AAPS
Division: PBPK

Purpose

  • Buccal delivery allows patient compliance, ease of drug administration and potential bypass of first-pass metabolism
  • Evaluation of buccal mucosal permeability may provide insights on the fraction absorbed in the oral cavity impacting the pharmacokinetic (PK) of drug products (DPs) delivered intraorally (IO)
  • A mechanistic in silico model was developed and validated in MembranePlus™ software (beta version, Simulations Plus Inc., Lancaster, CA) to deconvolute EpiOral™ in vitro permeability into drug diffusivity (Dm) and unbound fraction (fut) within the oral mucosa.
  • This study compares predicted Dm and fut for five DPs and their APIs, revealing formulation-driven differences in oral mucosal permeability.
  • This work enables in vitro to in vivo translation for IO absorption using physiologically based pharmacokinetic modelling (PBPK) framework.

By Priyata Kalra, Viera Lukacova, Pankaj Dwivedi, Khondoker Alam, Eleftheria Tsakalozou, Giovanni Pauletti, Haiying Zhou

American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 20-23, 2024, Salt Lake City, Utah