Why Bidose? Expanding Opportunities in Systemic Nasal Drug Delivery

Confidence in delivery-strategy decisions does not come from the format alone. It comes from understanding how therapeutic objectives, patient needs and dosing requirements work together.

The Questions Developers Are Asking Are Changing

For many years, discussions surrounding systemic nasal drug delivery were largely centred on rescue and emergency therapies.

This focus was understandable. The ability to provide rapid, non-invasive administration made the nasal route particularly attractive when speed and ease of use were critical. As a result, many of the most recognised intranasal products were developed around single-administration treatment paradigms. Nasal delivery became strongly associated with emergency response, acute intervention and rescue medicines.

Today, however, the conversation is evolving.

While rescue applications remain important, pharmaceutical developers are increasingly exploring how the nasal route can support a broader range of treatment strategies. From CNS disorders and cardiovascular indications to specialty therapies and lifecycle management opportunities, systemic nasal delivery is becoming a platform for innovation rather than a niche route reserved for emergencies.

As these opportunities expand, the questions developers ask during platform selection are changing as well.

Rather than simply asking:

Can this therapy be delivered intranasally?

Development teams are increasingly asking:

Which delivery format best supports the intended therapy, patient journey and commercial strategy?

It is this shift that is placing renewed attention on bidose nasal delivery systems. A BDS nasal delivery system provides two separately actuated metered doses from a single delivery system.

What Commercial Experience Is Teaching Us

The evolution of systemic nasal drug delivery is not merely theoretical. It is already visible in the types of products reaching the market.

Aptar Pharma’s nasal delivery platforms have been used in marketed nasal products for decades across a wide range of therapeutic areas, including migraine, seizure rescue, opioid overdose reversal, severe hypoglycaemia, cardiovascular care and CNS disorders. These products demonstrate that successful nasal therapies can have very different treatment objectives, administration environments and patient expectations.

One recent example is CARDAMYST™ (etripamil), approved for the treatment of paroxysmal supraventricular tachycardia (PSVT). Delivered using Aptar Pharma's Bidose System (BDS), the product illustrates how bidose delivery strategies can support the continued expansion of systemic nasal delivery beyond traditional rescue scenarios and into additional therapeutic categories.

Together, Aptar Pharma's Unidose (UDS)and Bidose (BDS) platforms have contributed to marketed products spanning emergency care, CNS disorders, cardiovascular applications, migraine treatment and metabolic conditions. This breadth provides a unique perspective on how nasal drug delivery requirements continue to evolve.

These developments reveal an important trend: while the nasal route continues to serve critical emergency applications, developers are increasingly evaluating how different delivery formats can address a broader set of clinical and commercial requirements.

The Evolution of Systemic Nasal Delivery

One way to understand growing interest in BDS formats is to look at how the systemic nasal market itself has evolved.

Historically, systemic nasal delivery was largely associated with rescue and emergency therapies, where rapid administration and ease of use were paramount.

As confidence in the route increased, developers began exploring broader acute-care settings and treatment paradigms extending beyond traditional rescue use.

Today, companies are evaluating nasal delivery for an expanding range of therapeutic opportunities, where dosing strategies, treatment frequency and patient journeys may differ considerably from the first generation of nasal products.

In many respects, systemic nasal delivery is evolving from:

Rescue therapies → Acute therapies → Specialty therapies → Future opportunities

This evolution does not diminish the importance of UDS systems. Unidose formats remain the preferred choice for many rescue and emergency therapies where a single administration is closely aligned with the intended treatment paradigm. The continued success of UDS products in areas such as opioid overdose reversal, seizure rescue and severe hypoglycaemia demonstrates that there is no universally superior delivery format. Instead, the optimal approach depends on the clinical, patient and commercial requirements of the product under development.

At the same time, the increasing diversity of nasal therapies is creating new questions around treatment flexibility, administration patterns and patient experience. Having supported products across both UDS and BDS platforms, Aptar Pharma has observed that format selection is becoming increasingly strategic as developers move beyond traditional rescue applications. Rather than choosing between UDS   and BDS in isolation, teams are increasingly evaluating which delivery strategy best supports the overall product profile. It is within this context that BDS delivery systems are attracting renewed interest.

Why Developers Are Taking a Second Look at Bidose

The growing interest in BDS delivery is not simply about providing two doses instead of one.

It reflects a broader shift towards greater flexibility in product design and more patient-centered treatment strategies.

A BDS system can offer developers additional options when designing products intended for episodic use, repeat acute administration, or treatment pathways where access to more than a single administration may provide advantages.

Importantly, the value of a BDS approach should always be assessed in the context of the intended therapy.

Having supported marketed products across multiple therapeutic areas, Aptar Pharma has observed that delivery-format requirements often differ significantly between applications. A system designed for a life-saving rescue treatment may have very different requirements from one intended for cardiovascular use, CNS therapy or other specialty-care indications.

In our experience, the most successful platform-selection decisions are rarely driven by delivey system features alone. They are driven by a clear understanding of:

• Therapeutic objectives
• Patient needs
• Administration environment
• Formulation requirements
• Regulatory considerations
• Long-term commercial strategy

Viewed through this lens, BDS delivery becomes less of a delivery feature and more of a development strategy.

The Rise of Patient-Centred Treatment Paradigms

Another factor contributing to growing interest in BDS formats is the industry's increasing focus on patient experience.

Over the past decade, pharmaceutical development has steadily moved towards solutions that reduce barriers to treatment, simplify administration and improve usability.

For nasal drug products, this means considering not only whether a formulation can be delivered effectively, but also how the delivery experience aligns with real-world patient behavior.

Questions such as:

• How will the product be used?
• Under what circumstances will administration occur?
• What level of training should be expected?
• How important is treatment flexibility?
• What does the patient's treatment journey look like?

are becoming increasingly important during development.

These are not purely device questions.

They are product-strategy questions.

And they often influence format selection long before clinical development is complete.

Aptar Pharma’s Perspective: Three Questions Worth Asking Early

Based on Aptar Pharma's experience supporting marketed nasal drug products across multiple therapeutic areas, three questions consistently emerge when evaluating BDS delivery strategies:

1. Does the therapy benefit from treatment flexibility?

Not all treatments require access to multiple administrations, but those that do may benefit from considering BDS options early in development.

2. What does the real-world patient journey look like?

Rescue, acute, episodic, and specialty-care treatments each create different expectations for usability, convenience, and administration.

3. Which development risks can be reduced through early platform selection?

Decisions made during platform evaluation can influence human factors, regulatory planning, manufacturing readiness and commercialization pathways later in development.

Answering these questions early can help align delivery strategy with product objectives before committing significant development resources.

Looking Forward

The most interesting question facing the industry is no longer whether systemic nasal drug delivery works.

A growing number of marketed products have already demonstrated the potential of the route across multiple therapeutic areas. Aptar Pharma's experience spans applications in CNS disorders, cardiovascular care, migraine, seizure rescue, severe hypoglycaemia, opioid overdose reversal and other systemically acting therapies, illustrating how diverse the category has become.

Instead, the next phase of innovation will be shaped by how effectively developers match delivery formats to increasingly diverse treatment needs.

As systemic nasal delivery continues to move beyond traditional rescue applications, BDS systems are likely to play an increasingly important role in enabling that evolution.

For pharmaceutical developers, the question may no longer be:

Why nasal delivery?

But rather:

When does a BDS strategy make sense?

A BDS strategy may be particularly relevant for therapies requiring treatment flexibility, episodic administration or access to more than one administration during a treatment journey. However, the optimal format ultimately depends on therapeutic requirements, patient needs, formulation characteristics, regulatory strategy and commercialization objectives. The most successful approach is not to start with the device, but with the intended product profile and patient experience.

As systemic nasal drug delivery continues to evolve, the most important questions facing developers are becoming increasingly strategic. Beyond delivery format selection, companies must consider how changing patient needs, emerging therapeutic opportunities, advances in formulation science and new development approaches are reshaping the market. In our next article, we will explore the key trends influencing the future of nasal drug delivery and what they may mean for pharmaceutical developers.