Research Article
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Published Online: 18 June 2010

Drug Transport Across Pulmonary Epithelial Cell Monolayers: Effects of Particle Size, Apical Liquid Volume, and Deposition Technique

Publication: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Volume 23, Issue Number 3

Abstract

Background: Pulmonary cell cultures are increasingly used to predict in vivo drug absorption after inhalation, similar to intestinal cell culture models that have already been well established to predict oral drug absorption. In contrast to the intestinal barrier, however, the so-called air–blood barrier of the lung is covered only with a thin film of liquid, on which the aerosol particles are deposited. The aim of this study was to investigate the relevance of this apical liquid film on the drug absorption rate when deposited as a dry powder formulation on pulmonary epithelial cells in vitro.
Methods: Budesonide and salbutamol sulfate were chosen as model drugs, and for each drug three generic aerosol powder formulations were used. Filter-grown monolayers of the human bronchial epithelial cell line Calu-3 were used as a model, using various volumes of apical liquid.
Results and Conclusions: Although proven to be bioequivalent in vivo for each of the two drugs, the generic dry powder fomulations showed strikingly different epithelial transport rates in vitro, depending on the amount of apical liquid and the deposition technique, and suggesting that the dissolution of the aerosol particles in the apical liquid volume was rate limiting for the overall absorption rate. However, we found that the absorption rates of the formulations were similar after aerosolization and deposition in a multistage liquid impinger, which simulates more realistically the detachment of the drug crystals from the carrier lactose and their aerodynamic particle size-dependent deposition in the respiratory tract following inhalation from a dry powder inhaler. These data demonstrate the need for improved in vitro test systems to allow deposition of aerosol particles on the air–liquid interface cultivated cell monolayers by simultaneously taking into account aerodynamic properties.

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Information & Authors

Information

Published In

cover image Journal of Aerosol Medicine and Pulmonary Drug Delivery
Journal of Aerosol Medicine and Pulmonary Drug Delivery
Volume 23Issue Number 3June 2010
Pages: 119 - 127
PubMed: 20073555

History

Published online: 18 June 2010
Published in print: June 2010
Published ahead of print: 14 January 2010
Accepted: 21 September 2009
Received: 18 March 2009

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Authors

Affiliations

Michael Bur
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
Hanno Huwer
Department of Cardiothoracic Surgery, Völklingen Heart Centre, Völklingen, Germany.
Leon Muys
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
Claus-Michael Lehr
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.

Notes

Reviewed by:Marianne GeiserIgor Gonda
Address correspondence to:Claus-Michael Lehr, Ph.D.Biopharmaceutics and Pharmaceutical TechnologySaarland UniversitySaarbruecken,Germany 66123
E-mail: [email protected]

Author Disclosure Statement

For all authors no conflicts of interest exist.

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