By Hammad Irshad, Research Scientist
As drug development expands into increasingly complex therapeutic modalities, delivery strategy has become a critical factor in development success.
For many programs, inhalation is still treated as a formulation challenge to address later in development. Yet for inhaled products, success depends on much more than the therapeutic itself. Formulation, aerosolization, deposition, device selection, and dose delivery all influence whether a promising therapy can successfully advance toward the clinic.
This disconnect between therapeutic development and delivery planning is what I often refer to as the inhalation gap.
Inhalation Science Has Entered a New Era
Aerosol science and inhalation science are closely related but distinct disciplines. Aerosol science encompasses all airborne particles, from environmental pollutants to aerosolized consumer products. Inhalation science focuses specifically on delivering compounds to the targeted regions of the respiratory system as part of pre-clinical and clinical studies.
That distinction matters because inhalation science has evolved far beyond traditional respiratory therapies.
While inhaled medicines have long been associated with asthma and COPD, today’s development pipeline includes gene therapies, biologics, RNA-based treatments, neurological applications, and rapid-onset therapeutics. Researchers are exploring increasingly precise approaches to deliver compounds to specific regions of the respiratory tract, creating opportunities that extend well beyond conventional pulmonary medicine.
The driving force behind this expansion is targeted delivery. By delivering a therapy directly to the intended site of action, inhalation can achieve meaningful local concentrations while limiting systemic exposure. This approach is particularly attractive for compounds where dose optimization and tissue targeting play an important role in therapeutic performance.
Interest is also growing in nasal delivery pathways. FDA-approved migraine therapies have demonstrated the potential of nose-to-brain delivery, opening new possibilities for future treatments targeting neurological and central nervous system disorders.
Why Delivery Feasibility Must Be Addressed Early
One of the most common challenges in inhalation development is that delivery feasibility is often evaluated after significant resources have already been invested in a therapeutic candidate.
The first question should be straightforward: Can the therapy be successfully aerosolized and delivered to the intended target region?
The answer varies considerably depending on the molecule and formulation. Small molecules often benefit from established aerosol generation approaches. More complex therapeutic platforms may present additional challenges involving stability, viability, and delivery performance.
Many organizations entering inhalation development underestimate the complexity of formulation development. Successful inhaled products require more than placing a compound into an inhaler or nebulizer. Particle characteristics, aerosol performance, stability of the product during aerosolization and deposition behavior all influence whether a therapy reaches the intended site of action.
Target location is equally important. Delivering a compound to the deep lung, conducting airways, upper respiratory tract, or nasal cavity requires different strategies. The delivery approach must align with the therapeutic objective from the beginning.
Four Questions Every Development Team Should Ask Early
Before entering preclinical development, teams should have clear answers to four critical questions:
- Can the compound be formulated into a stable, aerosolizable product?
- Where in the respiratory tract does the therapy need to be deposited?
- Will the formulation strategy support future clinical development?
- Can the required doses and safety margins be achieved through inhaled delivery?
Addressing these questions early helps reduce development risk and prevents costly redesign efforts later in the program.
Formulation Decisions Shape Long-Term Success
Formulation strategy is often the earliest make-or-break decision in inhalation development.
Choices surrounding liquid versus dry powder delivery influence stability, manufacturability, patient usability, and clinical translation. Early proof-of-concept studies can demonstrate biological activity, but proof-of-concept success alone does not guarantee a clinically viable product.
Development teams benefit from planning beyond the initial study. Clinical requirements, device strategy, manufacturing considerations, and patient use should all inform formulation decisions from the outset.
The history of inhaled insulin illustrates this principle. Early products demonstrated that inhaled insulin could work clinically, yet commercial adoption remained limited. More recent products have benefited from advances in device design and delivery technology, demonstrating how delivery strategy influences outcomes well beyond regulatory approval.
The Operational Realities of Inhalation Development
Inhalation programs differ substantially from traditional oral or injectable drug development.
One of the most common surprises for sponsors is the amount of material required for pre-clinical aerosol studies. Delivering targeted inhaled dose in pre-clinical studies frequently requires significantly more starting material than other routes of administration. These requirements can affect program cost, manufacturing timelines, and overall feasibility.
Regulatory expectations add another layer of complexity. Demonstrating safety margins above anticipated clinical exposures can be technically challenging for inhaled products, making early planning essential.
These realities highlight the value of involving inhalation specialists early. Collaboration among formulation scientists, aerosol engineers, toxicologists, and clinical teams helps identify practical limitations before they become development obstacles.
Looking Ahead
The future of inhalation science will be defined by two parallel trends: increasingly sophisticated therapeutics and increasingly sophisticated development tools.
Advanced in vitro models, organ-on-chip systems, and computational approaches are creating new opportunities to evaluate candidates earlier and with greater confidence. These technologies can improve candidate selection, accelerate development decisions, and support efforts to reduce reliance on animal studies.
At the same time, inhalation science continues to expand into new therapeutic areas where targeted delivery offers unique advantages.
As these trends converge, delivery strategy is becoming a core component of successful drug development. Organizations that integrate formulation, delivery, toxicology, and clinical planning from the earliest stages will be best positioned to translate promising therapies into successful products.
The most successful inhalation programs begin with a simple recognition: delivery is not a downstream consideration. It is a foundational element of development strategy.