How a dose reaches the lung
- Pulmonary drug delivery
- Pulmonary drug delivery administers medicine as an inhaled aerosol so the active compound can deposit on airway surfaces or in the alveolar region of the lung. Characterization testing describes the delivery event in terms of the device, the aerosol it generates, the aerodynamic size distribution, and the fraction of the emitted dose small enough to reach the lower airways.1,3,5
An inhaled therapy must do more than release a cloud. It must place a defined dose in a defined region of the airways. Whether the compound acts locally in the bronchi or is absorbed across the alveolar surface, the useful dose is the portion that deposits at its intended site, not the portion lost inside the device, in the mouth, or in the throat.1,5
The device classes that generate the aerosol
| Device class | How the aerosol forms | Typical characterization focus |
|---|---|---|
| Pressurized metered dose inhaler (pMDI) | A metered volume of propellant-based formulation flashes to an aerosol on actuation | Delivered dose, aerodynamic particle size, spray pattern, actuator behavior |
| Dry powder inhaler (DPI) | The patient's inspiratory flow disperses a powder blend into respirable particles | Delivered dose against flow rate, fine particle fraction, aerodynamic size |
| Nebulizer | Continuous or breath-actuated conversion of a liquid into a fine mist | Droplet size distribution, output rate, delivered dose over time |
| Soft-mist inhaler | Mechanical energy forces a solution through fine nozzles to form a slow-moving mist | Delivered dose, aerodynamic size, plume duration |
Device class depends on the compound, patient population, and dose, and each class calls for a different testing plan. In a pMDI, the formulation, metering valve, and actuator work as a system. A DPI depends on the patient generating enough inspiratory flow to disperse the powder. Nebulizers and soft-mist inhalers produce a mist, with output measured over the delivery period.1,4
What governs where the dose deposits
- Aerodynamic diameter
- Aerodynamic diameter is the diameter of a unit-density sphere that settles through air at the same velocity as the particle being evaluated. It combines physical size, shape, and density in a single value. As a result, aerodynamic size predicts how deeply an inhaled particle may travel into the airways more effectively than geometric size alone.3,5
- Inertial impaction dominates for larger, faster particles, generally above about 5 µm aerodynamic diameter, and deposits them in the mouth, throat, and large conducting airways where air velocity is high.5
- Gravitational sedimentation acts on particles of roughly 1 to 5 µm during the slower flow and any breath-hold in the smaller airways, making this size band useful for reaching the conducting and peripheral airways.5
- Brownian diffusion governs very fine particles below about 0.5 µm, which reach the deep lung by random motion but can also be exhaled before they settle.5
Breathing pattern and airway geometry shift the balance among these deposition mechanisms. A fast, forceful inhalation increases impaction losses in the throat. A slower, deeper breath followed by a breath-hold gives particles more time to settle in the peripheral airways. Airway narrowing, branching angle, and individual anatomy also affect deposition. Together, these effects make the inhalation profile a study variable to control rather than leave to chance.4,5
Formulation considerations
Formulation choices directly affect the aerosol leaving the device. Suspension and solution formulations behave differently as they age, while carrier particles in a powder blend influence how the fine drug particles disperse. Propellant and co-solvent choices affect droplet evaporation and final particle size. Hygroscopic particles may also absorb water in the warm, humid airways and grow after inhalation, changing where they deposit.1,2
How ARE Labs characterizes inhaled products
ARE Labs focuses on the in-vitro characterization of pulmonary drug delivery. The laboratory measures what a device and formulation emit and how that aerosol is distributed by size; it does not run clinical or in-vivo studies. A typical program combines breathing simulation and delivered-dose measurement with aerodynamic particle sizing by cascade impaction. Together, these measurements show how much active compound leaves the device and how the emitted dose is distributed across the aerodynamic size range.1,3,4
ARE Labs is an aerosol characterization laboratory, so its results describe device and formulation performance under defined laboratory conditions. The resulting data can inform development, product comparisons, and quality decisions, but they are considered alongside the clinical and regulatory work performed outside a characterization laboratory.3,4
What to define before requesting testing
- Name the device class, such as pMDI, DPI, nebulizer, or soft-mist inhaler, and whether the study supports development, a comparison, quality control, or design verification.1,4
- State the priority endpoint first: delivered dose, aerodynamic particle size distribution, fine particle fraction, or output over time.1,3
- Define the inhalation profile, flow rate, number of doses, and any beginning, middle, and end-of-unit sampling positions the plan needs.1,3
- Identify the formulation type and any stability or aging condition, since suspension state and storage can move particle size and delivered dose.1,2