How a dose reaches the lung
- Pulmonary drug delivery
- Pulmonary drug delivery is the administration of a medicine as an inhaled aerosol so that the active compound deposits on the airway surfaces or in the alveolar region of the lung. In characterization testing, the delivery event is described by the device, the generated aerosol, the aerodynamic size distribution, and the fraction of the emitted dose small enough to reach the lower airways.1,3,5
The target of an inhaled therapy is not simply to release a cloud, but to place a defined dose in a defined region of the airways. Whether a compound acts locally in the bronchi or is absorbed across the alveolar surface, the useful dose is the part that deposits where it is intended, rather than the part 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 is chosen for the compound, the patient population, and the dose, and each class shifts the testing plan. A pMDI ties formulation, metering valve, and actuator together. A DPI depends on the patient generating enough inspiratory flow to disperse the powder. A nebulizer and a soft-mist inhaler each report output as a mist 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 in air at the same velocity as the particle in question. It folds physical size, shape, and density into one value, which is why aerodynamic size, not geometric size, predicts how deep in the airways an inhaled particle travels.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 move the balance among these mechanisms. A fast, forceful inhalation raises impaction losses in the throat, while a slow, deep breath with a breath-hold gives particles time to settle in the periphery. Airway narrowing, branching angle, and individual anatomy also change the deposition pattern, which is one reason inhaled product testing controls the inhalation profile rather than leaving it to chance.4,5
Formulation considerations
Formulation decisions feed directly into the aerosol that leaves the device. Suspension and solution formulations behave differently as they age, carrier particles in a powder blend control how the fine drug particles disperse, and propellant or co-solvent choices affect droplet evaporation and the final particle size. Hygroscopic particles can also take up water in the warm, humid airways and grow after they are inhaled, shifting where they deposit.1,2
How ARE Labs characterizes inhaled products
ARE Labs works on the in-vitro characterization side of pulmonary drug delivery: measuring what a device and formulation emit and how that aerosol is sized, not running clinical or in-vivo studies. A typical program pairs breathing-simulation and delivered-dose measurement with aerodynamic particle sizing by cascade impaction, so a team can see both how much active leaves the device and how that dose is distributed by size.1,3,4
Because ARE Labs is an aerosol characterization laboratory, its results describe device and formulation performance under defined laboratory conditions. They inform development, comparison, and quality decisions, and they are read alongside the clinical and regulatory work that sits outside a characterization lab.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