Pulmonary drug delivery has become an increasingly important route of administration for treating respiratory diseases, delivering medication directly to the lungs with potential for systemic delivery. Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) are among the most widely used inhalation platforms due to their portability, propellant-free design and ability to efficiently deliver medication to the respiratory tract. However, the very characteristics that make inhalation products effective also make them particularly vulnerable to environmental conditions.
For inhalation formulations to reach the deep lung, particle size typically needs to be in the 1-5 μm range. These fine particles are inherently cohesive and prone to agglomeration, making formulation stability a critical consideration throughout development, manufacturing, storage, and use. Unlike many conventional oral solid dosage forms, relatively small changes in moisture exposure can significantly alter the physical properties of inhalation powders, resulting in changes in dose delivery and aerosol performance.
Inhalation products are complex systems consisting of:
| Active Pharmaceutical Ingredient (API) | Typically micronized/spray dried to achieve the particle size necessary for pulmonary deposition. |
| Carrier-Based Formulations | Many DPIs use lactose-based carrier particles to improve powder handling and dose metering. The drug particles detach from the carrier during inhalation and are transported into the respiratory tract, while lactose particles will deposit in the upper airways/throat. |
| Capsules, Blisters, or Reservoir Systems | The formulation may be contained within capsules, blister packs, or multidose reservoir devices, each presenting unique stability considerations. |
| Device Components | Plastic and polymeric components must maintain dimensional stability and performance characteristics throughout the product lifecycle. |
Because these elements interact with one another, maintaining a controlled package microenvironment is often essential to preserving product performance.
One of the most common challenges in inhalation development is moisture uptake by the powder formulation. Exposure to elevated humidity can increase particle cohesiveness and adhesion forces, causing particles to form agglomerates. As a result, the powder may not disperse effectively during inhalation, reducing the respirable fine particle fraction reaching the deep lung. Potential consequences include:
Excessive humidity may also accelerate:
These changes can compromise both product efficacy and shelf life.
While moisture is often viewed as the primary threat, overly dry conditions can create their own problems. Very low humidity environments can increase electrostatic charging of powders and device components. Electrostatic interactions may cause particles to adhere to capsules, inhaler surfaces, or packaging materials, reducing emitted dose consistency, where this is more severe for micronized APIs. Strategies to control include grounding processing equipment and having rest cycles for blends prior to filling.
Many capsule-based DPI systems rely on gelatin capsules. When humidity levels become too low, capsules can lose moisture and become brittle, increasing the risk of cracking or fragmentation during device actuation. Capsule breakage can negatively impact dose delivery and patient experience.
Humidity fluctuations can impact plastic inhaler components and powder-device interactions. Changes in material properties or increased powder adhesion can contribute to:
Historically, the industry has relied heavily on desiccants to protect inhalation products by reducing package moisture. While this approach can prevent moisture-related degradation, it may not always provide the optimal environment for inhalation products. In some cases, driving humidity too low can contribute to electrostatic charging, capsule brittleness, or other performance challenges.
The goal should not always be the driest possible package. The goal should be maintaining the right humidity level for the formulation and delivery system.
Benefits for Inhalation Products
EQIUS is available as packets, capsules, stoppers and bags - allowing flexibility across a wide range of inhalation packaging configurations.
For moisture-sensitive DPI formulations, establishing and maintaining the optimal humidity window can significantly improve long-term product stability and performance.
For inhalation products where moisture ingress is the primary concern, DryGuard moisture protection systems provide a straightforward, drop-in moisture control solution.
DryGuard canisters are rigid desiccant units designed for high-speed pharmaceutical packaging lines. Benefits include:
DryGuard Packets provide flexible moisture protection for bottle and pouch applications. Benefits include:
Effective inhalation stability programs should consider:
Predictive modeling tools can also help identify optimal packaging configurations before extensive stability testing is conducted, reducing development time and experimental burden.
For inhalation products, stability is about far more than meeting a shelf-life specification. It is directly linked to delivered dose, aerosol performance, device functionality and ultimately patient outcomes.
Because both excessive humidity and excessive dryness can compromise product performance, inhalation manufacturers must carefully manage the package microenvironment. Solutions such as EQIUS Equilibrium RH Stabilizers offer a targeted approach by maintaining a specific humidity range, while DryGuard canisters provide proven protection against moisture ingress where traditional desiccation is required. Together, these technologies help manufacturers protect inhalation products from development through commercialization, ensuring consistent performance throughout the product lifecycle.
Why is moisture control important for dry powder inhalers?
Moisture can cause powder agglomeration, reduced aerosolization, inconsistent dosing, and chemical degradation, all of which may negatively impact inhaler performance and patient outcomes.
Can inhalation products become too dry?
Yes. Excessively dry conditions can increase electrostatic charging, promote powder adhesion to device components, and make gelatin capsules brittle.
What is the difference between EQIUS and a traditional desiccant?
Traditional desiccants continuously remove moisture. EQIUS maintains a predefined equilibrium relative humidity range by both adsorbing and releasing moisture as needed.
Which inhalation products can benefit from EQIUS?
EQIUS is particularly suitable for dry powder inhalers, capsule-based inhalation products, and other formulations that require a controlled humidity environment to maintain stability and performance.
When should DryGuard be used?
DryGuard is appropriate when moisture ingress is the primary stability concern and a low-moisture package environment is required to protect the product.
How can packaging help improve inhalation product stability?
Packaging can control the package microenvironment, reducing exposure to humidity and oxygen, protecting the formulation, maintaining device functionality, and supporting consistent dose delivery throughout shelf life.