The development and validation of an in vitro airway model to assess realistic airway deposition and drug permeation behavior of orally inhaled products across synthetic membranes

Bao K. Huynh, Daniela Traini, Dale R. Farkas, P. Worth Longest, Michael Hindle, Paul M. Young

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Current in vitro approaches to assess lung deposition, dissolution, and cellular transport behavior of orally inhaled products (OIPs) have relied on compendial impactors to collect drug particles that are likely to deposit in the airway; however, the main drawback with this approach is that these impactors do not reflect the airway and may not necessarily represent drug deposition behavior in vivo. The aim of this article is to describe the development and method validation of a novel hybrid in vitro approach to assess drug deposition and permeation behavior in a more representative airway model. Methods: The medium-sized Virginia Commonwealth University (VCU) mouth-throat (MT) and tracheal-bronchial (TB) realistic upper airway models were used in this study as representative models of the upper airway. The TB model was modified to accommodate two Snapwell® inserts above the first TB airway bifurcation region to collect deposited nebulized ciprofloxacin-hydrochloride (CIP-HCL) droplets as a model drug aerosol system. Permeation characteristics of deposited nebulized CIP-HCL droplets were assessed across different synthetic membranes using the Snapwell test system. Results: The Snapwell test system demonstrated reproducible and discriminatory drug permeation profiles for already dissolved and nebulized CIP-HCL droplets through a range of synthetic permeable membranes under different test conditions. The rate and extent of drug permeation depended on the permeable membrane material used, presence of a stirrer in the receptor compartment, and, most importantly, the drug collection method. Conclusions: This novel hybrid in vitro approach, which incorporates a modified version of a realistic upper airway model, coupled with the Snapwell test system holds great potential to evaluate postairway deposition characteristics, such as drug permeation and particle dissolution behavior of OIPs. Future studies will expand this approach using a cell culture-based setup instead of synthetic membranes, within a humidified chamber, to assess airway epithelia transport behavior in a more representative manner.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalJournal of Aerosol Medicine and Pulmonary Drug Delivery
Volume31
Issue number2
DOIs
Publication statusPublished - 1 Apr 2018
Externally publishedYes

Keywords

  • ciprofloxacin-hydrochloride (CIP-HCL)
  • drug permeation
  • in vitro test methods
  • realistic physical airway models
  • synthetic permeable membranes

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