Use of computational fluid dynamics deposition modeling in respiratory drug delivery

ABSTRACT

Introduction: Respiratory drug delivery is a surprisingly complex process with a number of physical and biological challenges. Computational fluid dynamics (CFD) is a scientific simulation technique that is capable of providing spatially and temporally resolved predictions of many aspects related to respiratory drug delivery from initial aerosol formation through respiratory cellular drug absorption.

Areas covered: This review article focuses on CFD-based deposition modeling applied to pharmaceutical aerosols. Areas covered include the development of new complete-airway CFD deposition models and the application of these models to develop a next-generation of respiratory drug delivery strategies.

Expert opinion: Complete-airway deposition modeling is a valuable research tool that can improve our understanding of pharmaceutical aerosol delivery and is already supporting medical hypotheses, such as the expected under-treatment of the small airways in asthma. These complete-airway models are also being used to advance next-generation aerosol delivery strategies, like controlled condensational growth. We envision future applications of CFD deposition modeling to reduce the need for human subject testing in developing new devices and formulations, to help establish bioequivalence for the accelerated approval of generic inhalers, and to provide valuable new insights related to drug dissolution and clearance leading to microdosimetry maps of drug absorption.

KEYWORDS:

• Pharmaceutical aerosols
• inhalers
• CFD simulations
• airway models
• aerosol deposition
• aerosol dosimetry
• bioequivalence
• complete-airway modeling
• whole-lung CFD modeling

Article highlights

• Computational fluid dynamics (CFD) is a scientific simulation technique that is capable of providing spatially and temporally resolved predictions of many aspects related to respiratory drug delivery.

• A key to successful use of CFD is conducting an analysis concurrent with in vitro experiments.

• Regional deposition models have provided an improved understanding of pharmaceutical aerosol delivery for several decades.

• Complete-airway deposition modeling is now being used in some cases to better understand existing respiratory drug delivery techniques and to develop new targeted delivery strategies.

• New strategies in development using concurrent analysis include controlled condensational growth and nose-to-lung aerosol administration for infants and children.

• We envision future applications of CFD deposition modeling to reduce the need for human subject testing in developing new devices and formulations, to help establish bioequivalence for the accelerated approval of generic inhalers, and to provide valuable new insights related to drug dissolution and clearance leading to microdosimetry maps of drug absorption throughout the lungs.

Declaration of interest

Virginia Commonwealth University is currently pursuing patent protection of excipient enhanced growth aerosol delivery, aerosol generation devices and patient interfaces, which if licensed, may provide a future financial interest to the authors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development under Award Number R01HD087339 and by the National Heart, Lung, and Blood Institute under Award Numbers R01HL139673 and R01HL107333. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.