Dry Powder Inhalers (DPIs) are an important tool for the treatment of a growing list of respiratory conditions, with recognized potential to deliver systemic treatments. Millions of people suffer from asthma and Chronic Obstructive Pulmonary Disease (COPD), and many of these patients rely on inhaled pharmaceutical treatments for relief. Drug delivery by inhalation can offer rapid onset of action, portable and non-invasive administration, and local delivery to the site of absorption, which can help to minimize the amount of API required. These proven benefits have led to new potential applications for systemic drug delivery, with indications for treatments of migraines, diabetes, Parkinson’s, cystic fibrosis, pulmonary hypertension and anti-infectives as examples.
Capsule-based DPIs can bring a myriad of benefits over propellant-based inhalation devices and nebulizers:
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Environmental benefit: Capsule-based DPIs can reduce a drug’s carbon footprint by up to 98% compared to traditional pressurized metered dose inhalers (pMDIs) using conventional propellants.
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Ease of use: Unlike pMDIs, which require coordinated actuation and breathing, capsule-based DPIs are breath-actuated, improving ease of use for patients.
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Formulation stability: Dry powder formulations used in DPIs are often more stable than liquid formulations, potentially leading to longer shelf life.
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Clinically appropriate and cost-efficiency: DPIs can be a more cost-effective alternative to pMDIs.
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Molecule versatility: They are increasingly suitable for a wider range of molecule types, expanding therapeutic potential.
So, the advantages of DPIs are clear, but what are the challenges in developing a new inhaled drug product based on a capsule-based DPI? As DPIs are considered a drug device combination product, their development requires specialized knowledge and experience to efficiently meet the various requirements of a program, including regulatory aspects. This can be achieved with in-house expertise, or by partnering with a specialist CDMO that has the necessary knowledge and capabilities in the below key areas:
1. Analytical characterization
Having the right analytical capabilities to fully characterize complex powder formulations and how they interact with the chosen device is critical to the development of a successful DPI device.
Aerodynamic characterization
Aerodynamic characterization is necessary to demonstrate that the drug device combination can deliver the desired aerodynamic performance to reliably deliver the right dose of powder formulation to the lungs. This can include determining delivered dose uniformity (DDU), aerodynamic particle size distribution (APSD), fine particle mass (FPM) or fine particle fraction (FPF) parameters.
Solid state characterization
Solid-state characterization is essential for all raw materials to ensure control over the final drug product. Parameters such as crystallinity, salt selection, surface roughness, and specific surface area help development scientists evaluate the complex interactions between APIs and carrier molecules. These factors can directly influence fine particle mass (FPM) and ultimately affect product performance.
Use of impactors
Impactors can be used in the laboratory to determine a number of these parameters, including APSD and FPM. The Anderson Cascade Impactor (ACI) can separate up to 10 different particles sizes, albeit through a time-consuming and manual testing process, while next-generation impactors (NGIs) can measure the deposition of multiple particle sizes simultaneously via a single horizontal tray.
As powders are affected by temperature, humidity, and electrostatic charge, these conditions must be controlled in the testing laboratory with specialized systems to avoid adverse effects on powder flow and aerosolization.
2. Capsule-based DPI regulatory experience
Because DPIs demand that device and drug formulation work in harmony to efficiently deliver powder to target areas of the respiratory tract, the regulations governing their development and marketing can be complex. Although somewhat harmonized, there are subtle differences in how different major regulatory bodies, such as the European Medicines Agency (EMA) or U.S. FDA, measure and determine bioequivalence of DPI products. From DDU, APSD to mass balance approaches, DPI development scientists need to know how to generate scientific data that will support the specific requirements of each agency. The demonstration of bioequivalence of a new DPI product with reference products includes analysis of the safety profile, drug delivery performance, airflow resistance, and human device handling factors, all of which must be put together in clear, submission-ready formats. Even after a DPI is launched, changes such as adding new carrier suppliers, capsule suppliers, or altering device materials can mean seeking post-approval regulatory approvals. Having the knowledge to navigate these sometimes-complex requirements is essential for DPI products.
3. Manufacturing capsule-based DPIs
Efficient manufacturing is critical to a successful launch and reliable supply of a capsule-based DPI product. For example, DPIs need to be manufactured using specialized dispensing suites that can minimize the loss of static micronized powder blends through efficient transfer steps that reduce valuable API and formulation losses. Development and Operations specialists should also consider the order they add raw materials or carry out powder processing steps like sieving as they can have an effect on deagglomeration. Electrostatic charge introduced during the capsule filling steps can also have a major impact on the aerodynamic behavior of the powder and capsules. A DPI manufacturer must have sufficient control over conditions in the manufacturing area, including temperature, humidity, and implemented isolators for high levels of environmental control to achieve consistent powder fills.
Barberà del Vallès: Your partner for manufacturing of dry powder inhalers
Choosing a partner that truly understands the critical aspects of developing inhalation products and has a proven track record of supplying them on a global scale is essential in efficiently bringing DPI products to market.
Our Barberà del Vallès site, located outside Barcelona, Spain, offers end-to-end manufacturing of complex oral solid and inhalation products. Its specialized high-containment inhalation manufacturing with advanced product dispensing capabilities and state-of-the-art packaging services offer complete DPI manufacturing capabilities.
Barberà del Vallès is part of Siegfried's network of 13 sites globally. Siegfried is a leading CDMO offering development and manufacturing of pharmaceutical ingredients and finished dosage forms as an integrated supplier. Partnering with Siegfried’s team of experts brings decades of experience together with the specialized capabilities needed to rapidly advance today’s DPI programs.
If you are interested in learning more about the Barberà del Vallès and its capabilities, contact us:
