In Vitro Oral Cavity Permeability Assessment to Enable Simulation of Drug Absorption

Area of Science:

• Pharmacology
• Drug Delivery
• Biotechnology

Background:

• The oral cavity offers a convenient drug administration route, bypassing hepatic first-pass metabolism.
• Selected active pharmaceutical ingredients (APIs) were investigated in U.S. Food and Drug Administration-approved oral cavity drug products.

Purpose of the Study:

• To quantify the mucosal permeation properties of APIs in oral cavity drug products.
• To evaluate human-derived sublingual (HO-1-u-1) and buccal (EpiOral™) in vitro tissue models for drug absorption studies.

Main Methods:

• Epithelial barrier properties were assessed using propranolol and Lucifer Yellow as markers.
• Transepithelial flux of APIs in artificial saliva (pH 6.7) was quantified via High-Performance Liquid Chromatography (HPLC).

Main Results:

• Apparent permeability coefficients (Papp) varied between APIs and tissue models.
• The buccal EpiOral™ model showed greater discrimination, with permeation values ranging from 3.31 ± 0.83 × 10⁻⁷ cm/s (acyclovir) to 2.56 ± 0.68 × 10⁻⁵ cm/s (sufentanil).
• Higher tissue-associated dose fractions were observed in the buccal EpiOral™ model (up to 8.5% for sufentanil).

Conclusions:

• Permeation data from in vitro models will train predictive computational models for oral drug absorption.
• In silico modeling strategies are expected to accelerate the development of generic oral cavity products.
• Model-integrated evidence will support regulatory decisions for generic drug development.