Susana Ecenarro, VP R&D Qualicaps EMEA, Roquette Health & Pharma Solutions shares thoughts on the growing global interest in inhaled drug delivery.
Roquette
1. What factors are driving the growing global interest in inhaled drug delivery?
The most influential factor raising the profile of inhaled therapies is simply increased demand. Worsening pollution in several regions combined with a growing global population have led to a steady rise in cases of asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis around the world. This is contributing to an expected 6.5% increase in the global market value for the pulmonary/respiratory drug delivery market by 2029. There are, however, some more positive forces at play. In many scenarios – such as the medication of patients who have difficulty swallowing – inhaled routes of administration offer a significant advantage. And yet, for the most part, these delivery forms are confined exclusively to the treatment of pulmonary diseases. We see this picture shifting in the near future as pharmaceutical developers explore a wider range of drug delivery formats beyond oral pills, capsules or liquids.
2. Why is inhalation still a lesser-known or underutilised route of administration in pharma, in comparison to oral dosage forms for instance, and how can these barriers be overcome?
Inhalation as a route of administration occupies an interesting position in the pharma world as it’s both widely recognised and lesser-known outside of a few specific uses. To give a brief definition, inhalational drug administration refers to the delivery of drugs to the respiratory tract via inhalation and the use of various devices, like metered dose inhalers, dry powder inhalers, and nebulisers. They are widely recognised to be highly effective therapies for respiratory diseases thanks to their targeted delivery to specific regions of the lung. Their other qualities though, such as rapid systemic absorption and rapid onset of action with a lower risk of side effects, are equally relevant for applications such as pain relief or neurological conditions. The main barrier to overcome in raising the profile of inhalation therefore is challenging the perception that it is only applicable to pulmonary medicine.
3. How do different inhaler technologies—like MDIs, DPIs, and SMIs—compare in terms of effectiveness, sustainability, and patient usability?
Inhaler technologies vary widely in terms of their delivery method, environmental impact and ease of use across patient groups. Metered dose inhalers (MDIs), for instance, use pressurised aerosols, making them highly portable, but their effectiveness relies heavily on the user’s coordination and timing. They also depend on aerosol propellants, such as hydrofluorocarbons (HFCs), a class of chemicals which contributes significantly to greenhouse gas emissions. Dry powder inhalers (DPIs), which are breath-actuated and propellant-free, offer a more environmentally sustainable option – producing up to 18 times less CO₂ than MDIs. Many patients also find these inhalers easier to use as they eliminate the need for timing their breaths with the administration of the dose. However, DPIs require adequate inspiratory effort and so may not be suitable for those with severe respiratory impairment. Soft mist inhalers (SMIs) bridge some of these gaps by releasing a slow-moving mist and requires less inspiratory effort. This makes them particularly useful for patients with limited lung strength.
As we can see, each device type offers its own strengths and limitations, making the judgment of an experienced clinician all the more vital for selecting the right option for an individual’s unique circumstances. As demand grows for therapies that marry effectiveness with sustainability, pharmaceutical developers are investing in some forms of inhalers to give clinicians and patients the widest selection possible.
4. What innovations in excipients are expanding the possibilities for inhaled drug formulations?
A shift in the way the industry approaches excipient selection is opening new possibilities for inhaled drug formulations, particularly in the case of dry powder inhalers (DPIs). While lactose remains the most commonly used carrier, it presents limitations – derived from dairy, it's a potential allergen, as well as being chemically reactive with certain APIs. Drawbacks like these have prompted drug developers to explore alternatives carriers like mannitol – a non-reducing sugar alcohol valued for its chemical and physical stability. Unlike lactose, it doesn’t contribute to the Maillard reaction, making it better suited for sensitive APIs, such as proteins and peptides. Its crystalline, non-hygroscopic nature helps maintain powder flowability and prevents aggregation, ensuring consistent dose delivery. And, importantly, mannitol can be engineered into specific particle sizes to enhance aerodynamic performance and deep lung deposition.
In tandem with carrier innovation, capsule materials are also evolving. Devices like Handihaler and Breezhaler inhalers employ capsules as a means of powder storage and dose measurement. Increasingly, however, formulators are running up against the limits of gelatin – the traditional material of choice for pharmaceutical capsules. With its hydrophilic nature, gelatin can attract and retain moisture from the air, potentially destabilising hydroscopic APIs. A promising alternative here is hydroxypropyl methylcellulose (HPMC) – it offers a plant-based excipient with lower moisture content and superior chemical stability. Even better, using mannitol and HPMC-based capsules together can significantly improve formulation performance, offering safer, more effective inhaled therapies with broader patient appeal.
5. Beyond asthma and COPD, what therapeutic areas could benefit most from advances in inhaled drug delivery?
While inhaled therapies are best known for treating asthma and COPD, their potential reaches far beyond respiratory diseases. DPIs, in particular, are gaining traction as platforms for systemic drug delivery, opening new therapeutic vistas for ambitious drug developers.
An especially promising application for DPIs is vaccine delivery. Inhaled vaccines can activate both mucosal and systemic immunity without the need for injections. This not only improves patient compliance but also enhances stability of the capsule formulation at room temperature, removing some of the complexities linked to cold chain management and distribution.
Another emerging area is the treatment of central nervous system (CNS) disorders. Although nasal delivery is usually thought of as the best method for targeting nose-to-brain mucosal barriers, pulmonary absorption also bypasses first-pass metabolism, enabling more efficient delivery of neurological drugs. Inhalation could also offer faster onset of action and improved pharmacokinetics, both of which are critical for managing conditions like epilepsy, migraines, or even anxiety.
As research and formulation technologies evolve, inhaled drug delivery is poised to play a transformative role well beyond the lungs – offering needle-free, fast-acting, and patient-friendly alternatives for a range of systemic therapies.
6. Looking ahead, what are the biggest opportunities for innovation in inhaled therapies over the next decade?
The outlook is bright, with major advancements expected in formulation science, device design, and systemic delivery. Expanding use of alternative excipients – like mannitol – will play a key role, allowing greater freedom when working with moisture-sensitive APIs, improving sensory properties and expanding the range of drugs suitable for pulmonary delivery.
Despite the perception that pharma moves slowly, inhaled drug delivery is rapidly advancing, driven by global demand for effective, accessible treatments tailored to patients’ needs. As drug developers and pharmaceutical scientists, it falls to us to turn this potential into practical reality.