Inhalation and Pulmonary Delivery

Inhalation delivers a drug as an aerosol of fine particles or droplets that the patient breathes in, depositing it within the airways and lungs. It serves both local treatment of respiratory disease and, because the lung offers a very large, thin, well-perfused absorptive surface, systemic delivery of selected drugs. Where the aerosol deposits, and therefore how the drug acts, depends heavily on particle size and breathing pattern.

Definition

Pulmonary delivery is administration of a drug as an inhaled aerosol that deposits within the airways or alveoli, used for local respiratory effect or for systemic absorption across the large alveolar surface.

Scope

This topic covers aerosol deposition in the respiratory tract, the role of particle size, the main inhaler device classes (pressurized metered-dose inhalers, dry powder inhalers, and nebulizers), and the distinction between local and systemic pulmonary delivery. It is a pharmaceutical reference and does not provide inhaler technique or treatment guidance.

Core questions

• How does aerosol particle size determine where a drug deposits in the respiratory tract?
• What distinguishes local airway delivery from systemic absorption through the lung?
• How do metered-dose inhalers, dry powder inhalers, and nebulizers differ as delivery devices?
• What makes the alveolar surface attractive for systemic delivery of macromolecules?

Key concepts

• Aerosol deposition
• Aerodynamic particle size
• Pressurized metered-dose inhaler
• Dry powder inhaler
• Nebulizer
• Local versus systemic pulmonary delivery
• Alveolar absorption

Mechanisms

An inhaled drug must be aerosolized into particles or droplets small enough to escape impaction in the upper airway yet large enough to deposit before being exhaled; the aerodynamic size, typically in the low-micron range, is the dominant factor governing where in the respiratory tract the drug lands (Patton & Byron, 2007). Particles depositing in the conducting airways act locally, whereas those reaching the alveoli encounter a very large, thin, highly perfused surface that can absorb drug rapidly into the systemic circulation, making the lung a route for systemic delivery of some molecules, including macromolecules. Device class shapes the delivered aerosol: pressurized metered-dose inhalers, dry powder inhalers, and nebulizers each generate aerosols differently and impose different formulation requirements. Carrier systems such as lipid-based particles have been explored to modify pulmonary release and retention (Cipolla et al., 2014).

Clinical relevance

Inhalation places drug directly at the respiratory site of action for airway disease and offers a non-invasive systemic route for selected drugs, and understanding deposition and device behavior supports appraisal of why inhaled products are formulated and selected as they are. This entry describes delivery principles for reference and is not a basis for inhaler selection, technique, or treatment in any individual.

Evidence & guidelines

Reviews of pulmonary delivery describe aerosol deposition, device classes, and the lung as a systemic route (Patton & Byron, 2007), and reviews of lipid-based pulmonary carriers cover formulation approaches for inhaled products (Cipolla et al., 2014). Standard pharmaceutics texts codify aerosol and inhaler design (Aulton & Taylor, 2018).

History

Inhaled medicines moved from simple nebulized solutions to the pressurized metered-dose inhaler in the mid-twentieth century and to dry powder inhalers thereafter. Interest in the lung as a systemic route, including for macromolecules such as inhaled insulin, grew from the late twentieth century, drawing attention to the alveolar surface as an absorptive site and to the central role of aerosol particle size (Patton & Byron, 2007).

Key figures

• John Patton
• Peter Byron
• Hak-Kim Chan

Seminal works

• patton-byron-2007
• cipolla-2014

Frequently asked questions

Why does particle size matter so much for inhaled drugs?

The aerodynamic size of the aerosol determines where particles deposit: large particles tend to impact in the mouth and upper airway, while only suitably small particles reach the deeper airways and alveoli where the drug is intended to act or be absorbed.

Can drugs reach the rest of the body through the lungs?

Yes; the alveolar surface is large, thin, and well-perfused, so some drugs deposited deep in the lung are absorbed into the systemic circulation, which is the basis for systemic pulmonary delivery.