Pulmonary drug delivery has long been associated with a familiar set of indications, particularly asthma and chronic obstructive pulmonary disease (COPD). Those conditions remain central to the inhalation market, but the boundaries of the field are beginning to shift. Researchers and developers are exploring inhalation delivery across a wider range of therapeutic categories and technologies, renewing attention on dry powder systems and other inhaled dosage forms. Globally, the inhalable drugs sector is projected to grow from roughly $36 billion in 2023 to nearly $60 billion by 2030 as new therapies and delivery approaches emerge.¹

The therapeutic landscape within traditional respiratory care has not changed as significantly as other therapeutic areas. Many widely used therapies still rely on combinations of established mechanisms, such as inhaled corticosteroids, long-acting beta agonists, and long-acting muscarinic antagonists. While device engineering and formulation improvements continue to refine these treatments, new pharmacological pathways remain relatively uncommon. However, many developers are looking to inhalation for opportunities beyond the conventional respiratory playbook.

Inhalation approaches are being explored for new therapeutic categories, including oncology, neuropsychiatric therapies, and advanced biologics. Many of these programs involve devices capable of delivering substantially larger powder payloads than traditional inhaled therapies, which often administer microgram quantities of active pharmaceutical ingredient (API) within carrier-based systems. Delivering tens of milligrams of powder directly to the lung raises new questions about aerosol performance, device architecture, and patient tolerability.

As a result, inhalation products must increasingly be designed as integrated systems in which particle engineering, formulation strategy, device architecture, and manufacturing considerations evolve together.

Inhalation Development Requires a System-Level Approach

A common misconception in inhalation development is that the formulation can be optimized first and the delivery device selected later. However, such a device is not simply a container or a method of administration; it plays a direct role in determining how the powder disperses, how the aerosol forms, and ultimately where the drug deposits in the respiratory tract.   Inhalation products are best understood as integrated systems in which formulation, particle properties, and device architecture must function together. Whenever possible, device and formulation development should proceed in parallel. Optimizing both elements together allows developers to understand how the formulation behaves within the intended delivery platform and identify performance limitations early. 

A common early strategy illustrates this challenge. Many developers begin inhalation programs using simple capsule-based platforms paired with widely available research devices. This approach is straightforward, commercially accessible, and familiar across the industry. Capsule-based formats allow teams to focus initially on powder engineering and aerodynamic particle size distribution (APSD) without committing to a proprietary device. 

However, the apparent simplicity of this strategy can become a liability later. If the program transitions from the capsule-based platform to a proprietary or bespoke device, the entire aerosolization mechanism may change. Device geometry, airflow resistance, and dispersion mechanisms all influence how the powder deagglomerates and exits the device. Even relatively small differences in these parameters can alter particle-size distribution and delivered dose, sometimes requiring additional analytical work or further safety evaluation if the performance profile shifts.

These risks highlight the importance of evaluating device performance early and under realistic operating conditions. Parameters such as device resistance influence how much inspiratory effort is required and how airflow develops through the inhaler, which in turn affects aerosol generation and lung deposition. Testing a formulation across multiple device configurations or airflow conditions can reveal performance differences that might otherwise remain hidden. In addition to standard cascade impactor measurements, developers may use breath simulators and anatomically realistic airway models to replicate patient inhalation profiles and better understand how aerosols behave in real use conditions. 

Engineering Inhalable Particles Requires Balancing Performance and Manufacturability 

Unlike many other dosage forms, where dissolution or systemic distribution may dominate the design process, inhalation therapies rely on precise control of particle properties to determine where a drug deposits in the respiratory tract. Aerodynamic particle size, density, morphology, and surface characteristics all influence how powders disperse and travel through the airways. These parameters determine whether particles remain in the upper airway, deposit in the bronchi, or reach the deep lung, making aerodynamic control fundamental to inhalation performance.²

Spray drying has become one of the most widely used tools for engineering inhalable particles because it allows developers to control particle size, morphology, and surface composition in ways that improve aerosolization. The technique has also attracted attention for inhalable biologics and other complex molecules that require carefully engineered particles to remain stable and dispersible during delivery.³ Achieving the desired aerodynamic profile requires tight control of formulation composition and process parameters, because morphology, residual solvent content, and surface energy all influence how powders behave after drying.⁴

Even when particle engineering produces powders that are optimized for inhalation, they may create manufacturing challenges. Highly micronized or spray-dried particles frequently exhibit poor flowability and strong cohesion unless combined with carrier systems like lactose. The same small particle size that enables effective aerosolization can complicate downstream processing, including powder handling, filling, and device loading.

These challenges may be compounded by electrostatics and humidity sensitivity. Fine powders can accumulate electrostatic charge and adhere to equipment or device surfaces, while humidity can alter particle adhesion and dispersion behavior. Moisture exposure may further influence stability and aerosol performance over time. If not carefully controlled, these factors can introduce variability during manufacturing and device filling.

Excipient selection introduces additional constraints. Materials that perform well in oral or parenteral formulations are not automatically suitable for pulmonary delivery. Certain excipients may irritate lung tissue, interfere with aerosolization, or fail to produce particles within the appropriate aerodynamic range. Developers must therefore select formulation components that are compatible not only with the drug substance but also with the physiological environment of the lung and the physical requirements of inhalation delivery.

When Devices and Formulations Do Not Align 

Even when a formulation demonstrates promising aerosol performance in early testing, the interaction between the powder and the delivery device can introduce new sources of failure. Aerosol generation depends on the interplay between airflow, device geometry, and powder behavior. If the dispersion mechanism does not align with the formulation properties, the system may deliver inconsistent doses or fail to disperse the powder effectively.

Retention within the device is a common manifestation of this mismatch. Capsule-based devices rely on airflow and mechanical puncturing to release powder from the capsule and disperse it into an aerosol. If the formulation exhibits strong cohesion or does not respond well to the device’s dispersion mechanism, a portion of the powder may remain trapped inside the capsule or device, reducing delivered dose even when laboratory testing suggests acceptable aerodynamic particle size distribution.

Powder adhesion and accumulation can introduce additional variability during repeated use. Material may adhere to internal surfaces and later release unpredictably, leading to fluctuations in delivered dose. These effects become particularly important in multi-dose devices, where developers must ensure that performance remains consistent across many actuations.

Material selection also plays an important role in device performance. Surface finish, polymer composition, and electrostatic properties influence how powders interact with internal components. Materials that accumulate electrostatic charge may promote particle adhesion, while electrostatically dissipative materials can reduce unwanted deposition inside the device.

Manufacturing transitions can introduce additional variability. Early prototypes are typically produced with soft tooling for rapid iteration, while later stages require hard tooling and multi-cavity molds for scale production. Even small differences in surface finish, dimensional tolerances, or airflow pathways during this transition can influence aerosol generation.

Device resistance is another parameter that affects both usability and performance. Dry powder inhalers rely on patient inhalation to disperse powder, and airflow resistance determines the effort required to generate aerosolization. Differences in resistance influence powder deagglomeration and may affect patient populations with limited inspiratory capacity.

Because inhalation products combine pharmaceutical and device elements, they are regulated as combination products. Developers must therefore evaluate device components not only for extractables and leachables but also for biocompatibility. 

Operational Realities of Inhalation Clinical Supply 

Formulation and device development receive most of the attention in inhalation programs, but clinical supply often becomes an equally important constraint as products move toward human studies. Because inhalation dosage forms typically involve device-based formats, they can create unique manufacturing, packaging, storage, and distribution challenges.

Single-dose or bespoke inhalation devices illustrate the issue clearly. Products delivered through pre-metered blisters or other specialized configurations may require filling, sealing, forming, and packaging operations that are difficult to automate during early development. As a result, filling, sealing, and packaging operations often remain partially manual at clinical scale, making early-stage manufacturing relatively labor intensive. Even when specialized filling equipment is available, the surrounding workflow may still depend on significant operator involvement.

The transition from early development processes to commercial manufacturing pathways introduces additional uncertainty. Some programs begin with laboratory-scale equipment, but later-stage clinical material may need to be produced using processes that more closely resemble eventual commercial manufacturing. If the early workflow is not sufficiently representative, developers may need to redesign equipment or establish new processes sooner than expected to support pivotal trials.

Packaging and storage also pose challenges. Device-based inhalation products are often physically larger than traditional dosage forms, which affects stability studies and storage capacity. Stability chambers that can hold large numbers of tablets or vials may fill quickly when the product consists of bulky device units. When the drug substance is controlled or high value, those storage demands can materially increase development costs.

Blinded trials add another layer of complexity. Device-based products may require labeling at multiple packaging levels while preserving the blind, pre-packaged units may need to be opened, labeled, and resealed before distribution. Each additional handling step adds cost and increases operational risk. For generic product development, the situation can be even more challenging because the delivery device itself may be difficult to blind, requiring additional strategies to maintain study integrity while preserving the functional characteristics of the reference product.

These realities make early coordination across formulation development, device manufacturing, and clinical supply essential. When those activities proceed in isolation, inefficient workflows and unnecessary repackaging often follow. Inhalation products remain device-driven even after the formulation performs as intended, and programs that recognize this early are better positioned to avoid costly operational surprises as development advances. 

Intranasal Powders Highlight Emerging Delivery Opportunities 

Interest in dry powder nasal delivery has grown steadily in recent years, reflecting the broader expansion of inhaled dosage forms beyond traditional respiratory medicine. Nasal delivery shares many technical features with pulmonary inhalation while offering distinct advantages for certain indications. The nasal mucosa enables rapid systemic absorption, making this route attractive for therapies that require fast onset of action or convenient administration outside of clinical settings.

Many current programs focus on single-dose rescue medications. Products such as naloxone and epinephrine illustrate the value of the nasal route in emergency situations, where treatment must be administered quickly and patients may not be able to inhale effectively. Nasal delivery enables rapid systemic exposure without requiring coordinated inhalation, and dry powder formulations may also offer stability advantages compared with liquids.

Most existing nasal powder devices are single-use and are discarded after administration. While this design works well for rescue medications, it becomes less practical for chronic therapies that require frequent dosing. The development of reliable multi-dose dry powder nasal platforms therefore represents an important innovation opportunity, though doing so requires advances in powder metering, device durability, and manufacturability.

Vaccines represent another intriguing application for nasal powder delivery. Dry powder formulations may provide stability advantages over liquid vaccines, particularly in settings where cold-chain logistics are difficult to maintain. Intranasal administration can also stimulate mucosal immune responses in the respiratory tract, potentially providing protection at the site where many respiratory pathogens first enter the body.

New Frontiers Raising the Stakes for Delivery Technology

The expansion of inhalation technologies into new therapeutic areas is beginning to reshape expectations for what pulmonary and nasal delivery systems can accomplish. While respiratory diseases remain the most familiar use case, developers are exploring inhalation as a platform for therapies that extend well beyond traditional bronchodilators and anti-inflammatory agents. As these applications evolve, the demands placed on particle engineering, device design, and manufacturing infrastructure are increasing.

One area receiving growing attention is oncology. Delivering anticancer therapies directly to the lung offers the possibility of concentrating drug exposure at the disease site while limiting systemic toxicity. Inhaled chemotherapy and other targeted approaches have been explored for lung tumors and pulmonary metastases, and early clinical research suggests localized delivery can achieve meaningful lung exposure while reducing systemic side effects.⁵ Achieving consistent lung deposition while maintaining manageable toxicity profiles places significant demands on inhalation formulation and delivery technology.

Inhalation is also being explored for therapies that benefit from rapid pharmacological onset. Psychedelic compounds are one example where pulmonary delivery could provide fast central nervous system exposure. Because inhalation allows rapid transfer of molecules into the bloodstream through the large surface area of the lung, it may support treatment approaches that rely on rapid onset and controlled therapeutic sessions. A growing pipeline of inhalable and nasal psychedelic candidates aimed at psychiatric and neurological conditions reflects this interest.⁶

Vaccines, biologics, and nucleic acid–based therapies represent another frontier for inhalation technologies. Macromolecules can often be formulated as inhalable powders through techniques such as spray drying, but more complex biological materials introduce additional challenges. Live attenuated viruses, bacteriophages, and cell-derived therapies may require biosafety infrastructure and containment strategies that differ from those typically used for small-molecule inhalation products. Delivering these materials safely while maintaining biological activity may require modifications to existing manufacturing systems and facility designs.

These emerging applications also place renewed emphasis on dose capacity. Traditional inhaled therapies often deliver microgram quantities of active pharmaceutical ingredient. New therapeutic classes may require substantially larger powder payloads to achieve clinical activity. Delivering tens of milligrams of finely engineered powder in a single administration is technically feasible but can strain existing device architectures and filling technologies. As a result, developers are exploring new inhalation devices capable of handling larger payloads and producing consistent aerosolization.

Among the more experimental concepts under discussion is dry powder nebulization. Conventional nebulizers generate aerosols from liquid formulations, while dry powder inhalers rely on patient inhalation to disperse the powder. A dry powder nebulization approach would combine elements of both systems, potentially allowing controlled aerosol generation without relying entirely on patient inhalation effort. Although still emerging rather than widely adopted, renewed interest in this concept reflects ongoing advances in powder engineering and device design. 

Capabilities Required for Successful Inhalation Development

The technical challenges associated with inhalation development make it difficult for any single discipline to address the problem in isolation. Particle engineering, device performance, manufacturability, and clinical supply planning are tightly interconnected, and decisions made in one area often influence outcomes in another. As a result, successful inhalation programs depend on close collaboration between drug developers and specialized partners capable of integrating these elements into a coherent development strategy.

This collaboration must go beyond conventional handoffs between organizations. In some development models, a formulation team may work independently for months before presenting results to the client. In inhalation programs, that approach often proves inefficient. Device design, aerosol testing, and formulation optimization often need to occur in parallel, with rapid feedback between teams as new data emerge. Effective partners therefore tend to operate comfortably in iterative environments where technical decisions evolve continuously during development.

Flexibility in project structure also plays an important role. Different developers approach inhalation programs with different expectations about how work should be organized. Some prefer clearly defined task-based arrangements in which each activity is scoped and priced individually, while others favor more open-ended research models that allocate a dedicated team and allow experiments to evolve as new insights emerge. Successful partners are typically able to support both approaches and adapt their operating model to the needs of the program.

Technical depth across multiple domains is equally important. Inhalation programs often begin with complex particle engineering challenges that require strong research and development capabilities, but those discoveries must ultimately translate into GMP-compliant manufacturing processes that support clinical development. Teams that excel at exploratory formulation work but lack experience in regulated manufacturing may struggle to convert promising laboratory results into viable clinical products.

Another critical but sometimes overlooked area is translational strategy. Inhalation toxicology and animal studies differ in important ways from other routes of administration. The way a compound is delivered to animal models does not always replicate how it will be administered in humans. Smaller laboratory species may require specialized aerosol generation systems or intratracheal dosing approaches, while larger animals may use devices that more closely resemble human inhalers. Development teams must therefore understand how early animal studies translate into human delivery and design experiments that generate meaningful regulatory data.

For dry powder inhaler programs in particular, effective partners typically combine expertise in particle engineering and formulation design, analytical tools for evaluating aerosol performance, and experience with the manufacturing challenges associated with fine powders and highly potent compounds. Operational capabilities, such as device filling strategies, packaging design, and clinical trial supply planning, are also essential. 

Successful Inhalation Programs Start with Integrated Development 

The growing interest in inhalation delivery reflects a broader recognition that the respiratory tract offers unique opportunities for both local and systemic therapy. Advances in particle engineering, device design, and formulation science have made it possible to consider inhalation approaches for a wider range of molecules and therapeutic goals than in the past. From traditional respiratory therapies to emerging areas such as oncology, neuropsychiatric treatments, and mucosal vaccines, the scope of inhalation development continues to expand.

At the same time, this expansion has revealed how demanding inhalation product development can be. Fine powders with the aerodynamic properties required for lung deposition often present significant manufacturing challenges. Device architecture strongly influences aerosol performance and patient usability. Clinical supply strategies must accommodate device-based dosage forms that introduce new operational and regulatory considerations. Each of these factors affects the others, creating a development environment where technical decisions cannot be made in isolation.

For developers entering the field, the temptation is often to treat inhalation as a formulation exercise: engineer the right particles, place them into a device, and move forward through the development pathway. Experience increasingly shows that this approach rarely captures the full complexity of the problem. Inhalation products are performance-driven systems in which formulation, device design, manufacturing processes, and clinical supply considerations must evolve together.

Programs that recognize this reality early are better positioned to navigate the challenges that arise as development progresses. When formulation scientists, device engineers, manufacturing specialists, and clinical supply teams work in coordination from the beginning, they can anticipate many of the issues that might otherwise surface late in development. This integrated approach reduces the risk of costly redesigns, unexpected regulatory hurdles, or operational bottlenecks as products move toward clinical evaluation.

As inhalation technologies extend into new modalities and therapeutic areas, this integrated mindset will become even more important. Delivering larger payloads, accommodating complex biologics, and supporting innovative device architectures will require close alignment between scientific discovery and practical implementation. The opportunity in inhalation drug delivery continues to grow, but success will increasingly depend on development strategies that treat inhalation not as a single technical challenge, but as a coordinated system from particle to patient.

References

1. Inhalable Drugs Market (2025 – 2030): Size, Share & Trends Analysis Report By Drug Class (Aerosol, Dry Powder Formulation, Spray), By Application (Respiratory & Non-Respiratory Diseases), By Region, And Segment Forecasts. Grand View Research. 2025
2. Vehring, Reinhard. “Pharmaceutical Particle Engineering via Spray Drying.” Pharm. Res. 25: 999–1022 (2007).
3. Alhajj, Nasser, Niall J O’Reilly, and Helen Cathcart. “Designing enhanced spray dried particles for inhalation: A review of the impact of excipients and processing parameters on particle properties.” Powder Technology. 384: 313–331 (2021).
4. Jüptner, Angelika and Regina Scherlieβ. “Spray Dried Formulations for Inhalation—Meaningful Characterisation of Powder Properties.” Pharmaceutics. 12: 14 (2020).
5. Rosière, Rémi, et al. “The Position of Inhaled Chemotherapy in the Care of Patients with Lung Tumors: Clinical Feasibility and Indications According to Recent Pharmaceutical Progresses.” Cancers (Basel). 11: 329 (2019). 
6. Rogueda, Philippe. “Transforming Mental Health Care: The Rise of Inhalable Psychedelics?” ONdrugDelivery. 170: 43–49 (2025).

Justin Lacombe, Ph.D., is Chief Scientific Officer at Experic, where he leads pharmaceutical development and engineering teams to address complex challenges in drug and combination product development. He specializes in process development, scale-up, and Quality-by-Design approaches, with deep expertise in powder dosing, formulation optimization, and primary packaging. Justin has extensive experience in inhalation products, including roles at Catalent Pharma Solutions and Teva, spanning particle engineering through fill/finish. He is a strong advocate for early-stage powder filling studies to reduce late-stage risk.

Brian Fagan is Vice President of Technical Sales at Experic, bringing more than 20 years of experience in clinical supply. He combines deep technical expertise with a strong commercial focus, partnering with clients to translate complex development, manufacturing, and clinical supply needs into practical, efficient solutions. Brian’s background spans operations, project management, quality, regulatory compliance, and global supply, enabling him to guide programs from concept through execution. His career includes roles at Shire (now Takeda), Fisher Clinical Services and Acculogix (both now Thermo Fisher Scientific); AdiraMedica; and Packaging Coordinators (now PCI).