Nasal delivery is attracting interest for both systemic therapies and drugs targeting the central nervous system (CNS). The nasal mucosa offers a route to systemic absorption that avoids first-pass metabolism, while delivery via the olfactory and trigeminal pathways is being explored as a way to reach the CNS. But a promising molecule and formulation are only part of the picture.
A nasal formulation may perform well in early testing yet prove difficult to deliver with the chosen device. A device may produce the intended spray characteristics in the lab but behave differently when patients use it. And a product that reaches the clinic can still face problems when it is scaled up for commercial manufacture.
These challenges are connected. A successful nasal drug delivery programme depends on getting the drug to the right place, making sure the formulation and device work together, and designing a product that can be manufactured at scale. A decision in one area can affect all the others.
Realising that potential requires decisions across several disciplines. Bespak®, the specialist contract development and manufacturing organisation (CDMO) focused on inhaled and nasal delivery, has formed a strategic collaboration with Upperton, a specialist formulation development CDMO. By bringing their capabilities together, the partners aim to help developers address interconnected formulation, device and manufacturing questions earlier in a programme.
In this article, we look at three decisions developers should make early to reduce rework and give a nasal drug product a clearer path to commercial supply.
Start with the delivery target
Before selecting a device or refining a formulation, developers need to define what the product must achieve. The drug’s intended therapeutic effect and defined patient population influence the target product profile. For a nasal product, that profile also needs to account for where in the nasal cavity the drug should be delivered.
This is particularly important when investigating nose-to-brain delivery. Reaching the intended region depends in part on the properties of the formulation and the droplets or particles produced by the device, alongside device usability and actuation consistency. Droplets must be suited to the delivery target without being carried into the lower airways. Rapid mucociliary clearance can limit the time a drug remains in contact with the nasal surface, while sensitive large molecules may require a delivery method that helps preserve their integrity.
These considerations cannot be resolved by formulation work alone. A change made to improve stability, solubility or residence time may affect device compatibility or how the product is manufactured. Equally, a device selected too early may restrict the formulations that can be used later.
Bespak’s new collaboration with Upperton allows formulation and device requirements to be assessed together from the outset. Upperton’s nasal product feasibility platform supports early formulation and device screening and initial assessment of likely product performance. This gives developers an opportunity to evaluate formulation strategy, delivery requirements and even future manufacturability before committing substantial time and resources to a particular approach.
Choose a device for the product and its users
Once the delivery target is clear, the next question is how to achieve it consistently. Device selection involves more than finding a platform capable of dispensing the formulation. Developers also need to consider how device performance may vary in real use.
If a small difference in insertion angle, depth or actuation changes where the dose is deposited, performance in controlled testing may not translate into reliable delivery for patients. Usability and performance consistency therefore need to inform device decisions alongside the molecule’s properties and the intended site of delivery.
Bespak’s portfolio gives developers access to established liquid, dry powder and soft mist delivery options across unit dose and multidose formats. Selecting from existing established platforms can provide a strong starting point for development, with optimisation focused on the needs of the formulation and patient. Through the collaboration, developers can access specialist delivery systems from device partners, including soft mist technology from Bespak’s joint venture Resyca®, and SNBL’s intranasal powder system.
One example is Resyca’s Ultra Soft Nasal platform. Its spray nozzle generates a slow-moving, low-shear aerosol, which can help protect sensitive molecules, including biologics, and support targeted deposition within the nasal cavity. The platform is also designed to reduce sensitivity to differences in insertion angle and depth, with slower, more controlled actuation to support consistent use. The platform has been developed to include both multidose and unit dose device options.
The right choice will depend on the product rather than a preference for any one technology. Bespak’s computational fluid dynamics and in-silico nasal modelling capabilities can help teams assess how different devices may perform against the intended delivery target before more extensive studies are initiated. Once a platform is selected, Bespak’s device optimisation processes, including further modelling and simulation supported by rapid prototyping, allow it to be tested and refined.
This early assessment can expose a mismatch between formulation, device and delivery target while there is still time to respond. It also helps teams focus development work on a solution that meets the product’s requirements, rather than discovering late in the programme that one element needs to be redesigned.
Consider manufacture before it becomes urgent
An approach that works at a small scale must eventually support clinical supply and, if development succeeds, commercial manufacture. Waiting until later stages to consider that transition can create avoidable risk and time-consuming rework.
Early formulation or device decisions may affect the materials, processes and controls needed at scale. The team must also generate the performance data required for regulatory submissions while refining the product and packaging for patient use. When these activities are handled separately, information can be lost during handovers, and manufacturing challenges may emerge after significant development work has been completed.
Bespak’s device engineering and commercial manufacturing capabilities can bring those later requirements into earlier decisions. Its Injection Moulding Academy provides small-scale manufacturing capability to help move a device towards scale-up and identify potential complexities before final industrialisation. Upperton contributes formulation development, analytical and GMP clinical manufacturing expertise, which then informs commercial manufacturing considerations as the finished product progresses towards launch.
Together, these capabilities give developers a way to evaluate with confidence whether the product they are designing can progress through clinical development and towards commercial supply. That may mean examining how a device will be made at greater volume, whether the formulation remains suitable for the proposed manufacturing process, or what evidence will be needed to support the product as it advances towards approval.
Keep the decisions connected
An integrated programme still needs clear ownership and communication. Under the collaboration, each customer is assigned a single commercial lead who remains a point of contact from early development through clinical supply and towards scale-up and manufacture. Customers can access the combined expertise of Bespak and Upperton regardless of which partner they approach first or the stage their programme has reached.
The value of that continuity is practical. A formulation decision can be reviewed with device performance in mind. A device can be evaluated against the target delivery site, patient population and product manufacturing requirements. When a challenge arises, the people addressing it have a shared understanding of the product and the decisions already made.
Nasal delivery offers possibilities for systemic and CNS drug development, but its promise depends on the performance of the complete drug-device combination. Considering delivery, usability and manufacture together from an early stage can help developers identify problems sooner and make more informed choices as a programme progresses.
For teams evaluating a nasal route, that is a useful place to start: define what the product needs to deliver, then make sure each development decision supports that goal through to commercial manufacture.
Developing a nasal drug-device combination product? Contact Bespak to discuss your programme today.
