In vitro investigation on the impact of airway mucus on drug dissolution and absorption at the air-epithelium interface in the lungs

Cingolani, Emanuela; Alqahtani, Safar; Sadler, Robyn C; Prime, David; Stolnik, Snjezana; Bosquillon, Cynthia

Abstract

Although the mucus layer is the first biological barrier encountered by inhaled drugs upon their deposition in the upper airways, its potential impact on drug dissolution and absorption in the lung has hardly been investigated. Bio-relevant in vitro models were therefore used to assess the role of airway mucus in the fate of drug particles at the air-epithelium interface. Salbutamol and indomethacin were used as model Biopharmaceutics Classification System (BCS) class III and class II drugs, respectively. Dry powders were reproducibly aerosolised using a PennCentury™ Dry Powder Insufflator onto multiple air-liquid interfaced layers of the broncho-epithelial cell line Calu-3 or thin layers of porcine tracheal mucus mounted onto Transwells® inserts, as well as on empty Transwells®. Comparison of the permeation profiles of the two drugs indicated that mucus acted as a barrier for salbutamol transport but increased that of indomethacin, suggesting it facilitates the dissolution of poorly soluble drugs. In presence of Calu-3 layers, the permeability of salbutamol was even more restricted while indomethacin transport was enhanced further. This study demonstrates mucus distinctly affects the absorption characteristics of drugs with different physico-chemical properties. Hence, drug-mucus interactions should be considered during the development of inhaled drugs.

Citation

Cingolani, E., Alqahtani, S., Sadler, R. C., Prime, D., Stolnik, S., & Bosquillon, C. (2019). In vitro investigation on the impact of airway mucus on drug dissolution and absorption at the air-epithelium interface in the lungs. European Journal of Pharmaceutics and Biopharmaceutics, 141, 210-220. https://doi.org/10.1016/j.ejpb.2019.05.022

• Journal Article Type: Article
• Acceptance Date: May 23, 2019
• Online Publication Date: May 30, 2019
• Publication Date: 2019-08
• Deposit Date: Jun 11, 2019
• Journal: European Journal of Pharmaceutics and Biopharmaceutics
• Print ISSN: 0939-6411
• Electronic ISSN: 1873-3441
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 141
• Pages: 210-220
• DOI: https://doi.org/10.1016/j.ejpb.2019.05.022
• Keywords: Biotechnology; Pharmaceutical Science; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/2172093
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0939641119303339
• Additional Information: This article is maintained by: Elsevier; Article Title: In vitro investigation on the impact of airway mucus on drug dissolution and absorption at the air-epithelium interface in the lungs; Journal Title: European Journal of Pharmaceutics and Biopharmaceutics; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ejpb.2019.05.022; Content Type: article; Copyright: © 2019 The Authors. Published by Elsevier B.V.