Demand for inhaled therapeutics continues to grow steadily. Metered-dose inhalers and dry powder inhalers are the first choice for treating respiratory diseases due to their patient-centered drug delivery. However, the development of DPIs presents significant challenges. How can optimal performance and shelf life be determined as early as possible in the development phase? Early prototyping and selecting the ideal desiccant provide the answers.
Against the backdrop of rising rates of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), pulmonary administration of drugs for systemic delivery continues to gain momentum. Dry powder inhalers (DPIs) have a decisive advantage over pressurized metered-dose inhalers (pMDIs): Drug delivery is patient-driven, allowing patients to coordinate dose delivery with inhalation. However, developing a successful DPI formulation for either localized or systemic effect is far from straightforward.
Challenges in DPI Development
To successfully reach the lower respiratory tract, active pharmaceutical ingredient particles must be smaller than five µm; the target range is generally one to five µm. However, particles in this size range tend to be both cohesive and adhesive and are therefore highly prone to agglomeration. Developing an effective DPI that delivers particles of the required size without an active drug delivery mechanism is consequently a significant challenge.
Although carrier-free formulations are an option, a common strategy is to bind fine active pharmaceutical ingredient particles to larger carrier particles measuring several tens of micrometers. During inhalation, the active pharmaceutical ingredient particles detach from the carrier, which then predominantly deposits in the mouth and throat due to its particle size. With this approach, the carrier makes up the majority of the resulting formulation, facilitating the handling and accurate dosing of the very small quantities of required active pharmaceutical ingredient.
Testing formulations in a prototype device is essential, as at this stage of product development there is still flexibility to adjust the properties of both the device and the formulation to achieve predefined drug delivery targets. DPI devices use complex internal geometries to convert the pressure drop generated by the patient during inhalation into the energy required to aerosolize the dose. The pressure drop across the device is a key differentiating characteristic of the device design.
Effects of Moisture on DPIs
In addition, DPIs must be protected from external influences, particularly moisture ingress. While they are often treated as a downstream challenge in pharmaceutical packaging, in reality, moisture ingress is among the most critical variables influencing drug stability, shelf life, and ultimately patient outcomes. Moisture content plays an important role in powder behavior and can have a significant impact on drug delivery from a DPI. However, excessively dry conditions can also be problematic due to increased electrostatic effects.
The optimum environment for a particular DPI in terms of moisture content depends on a range of physicochemical properties and can vary considerably from product to product. Particularly during product use, it is not always possible to avoid high or fluctuating humidity. However, moisture control that is well matched to the product requirements can ensure and optimize DPI performance during routine storage and use. For successful product development and application, it is therefore crucial to understand the impact of moisture on DPI efficacy and to take appropriate measures.
Effective Moisture Protection With Desiccants
The best protection strategy depends on the specific device. Essentially, there are three types of DPI: single-dose, multi-dose, and multi-dose reservoir devices. With a single-dose DPI, the patient inserts a capsule containing the formulation immediately before use. Multi-dose DPIs, on the other hand, are pre-filled with multiple doses, which are stored individually in compartments within a blister pack or cartridge. In a multi-dose reservoir device, the formulation is dispensed from a single reservoir at the time of use.
Each product type offers different options for moisture control. For example, capsules for single-dose DPIs are typically made from gelatin or hydroxypropyl methylcellulose (HPMC), which protect the formulation against moisture ingress. Primary packaging also provides good opportunities for moisture control. Adding desiccants to the DPI’s aluminum packaging, for example in the form of desiccant sachets, is also common practice to ensure the inhaler’s performance prior to first use.
Desiccants can also be integrated directly into the device itself, which are often silica gel or molecular sieves. Less commonly, a modified desiccant can be used, which can both absorb and release moisture. In all cases, the desiccant must be integrated into the DPI so that it cannot come into contact with the medication.
Collaboration From the Start
By using the right desiccant in one or more of these forms, DPI manufacturers can ensure product stability, extend shelf life, and at the same time maintain consistent performance throughout the product’s lifetime. Controlling moisture content in a DPI is critical, as it can significantly influence the drug delivery performance of the formulation. This requires technical expertise in desiccants and suitable packaging solutions, which should be incorporated into the development process as early as possible, turning moisture management from a packaging problem into a strategic advantage.
To benefit from this opportunity, DPI manufacturers need a partner who has profound expertise in moisture management, desiccant packaging, and the entire development process – from product design and development to design transfer and global production. Hence, the key to success lies in close collaboration with specialized Contract Design and Manufacturing Organizations (CDMO) to develop the optimal DPIs and packaging solutions for each specific application.
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