More than 235 million people worldwide suffer from asthma, according to the World Health Organization. So, when Italian pharmaceutical company, ChiesiFarmaceutici, developed a new medicine in the form of a powder, they turned to product development firm Cambridge Consultants for a revolutionary inhaler design. The result of the collaboration is the NEXThaler, a dry powder inhaler with an innovative design.
“Our brief from ChiesiFarmaceutici was to design an intuitive and simple to use inhaler. We started with a blank sheet of paper, and worked our way through a number of different concepts,” explains Matthew Allen, drug delivery program director at Cambridge Consultants.
Through brainstorming, Cambridge developed many ways to achieve the objective; however, the primary focus was to keep the device simple and easy to use.
Designing for Simplicity
“There were many stages of development,” explains Allen. The first stages included conversations and sketches on whiteboards. Next, the team began molding foam prototypes for handling. "We used engineering foam that was hand formed with a scalpel, that way we could have a physical model to demonstrate size and shape of different concepts.”
Using such prototyping tools allowed the designers to iterate models quickly, and to get physical designs into the hands of users for feedback. “As the concepts became more refined, we held early stage user studies using 'looks like' prototypes manufactured with stereolithography,” he adds. The proof of principle models were used to further test the functionality of the device.
The NEXThaler was then modeled using both ProENGINEER and SolidWorks CAD packages. ANSYS FLUENT Computational Fluid Dynamics (CFD) modeling software was used to design the aerosolization engine and air paths, and some finite element analysis (FEA) modules packaged with 3D CAD, were carried out early on to assist in designing the flexible features of the device. Finally, Cambridge Consultants used a Bespoke Software tool for statistical tolerance analysis. "These manufacturing techniques offer efficiency and fast turn around, which is useful during the development phase of a device,” says Allen.
The device comprises functional groups of components coupled together. The dosing mechanisms meter the drug from a reservoir, and the counting mechanisms, which include the breath actuated mechanism, activates the dosing group under a certain air flow, allowing the dose to be taken.
In the final stages of the design process, the team built two cavity injection mold tools and used the parts to verify the design. “In order to scale up the design to commercial level, further tools were built, including soft tools, to both explore the design space, investigate potential design improvements for scale up, and to build devices for development of the assembly process,” Allen adds.
Designing for simplicity, using the NEXThaler is easy. "All you have to do is open, inhale, and then close it; there is nothing else the patient has to do.” There is no active aerosolisation engine; instead, the aerosolization is produced by the patient breathing—a primary design challenge, according to Allen.
A reservoir inside of the device houses the medicine, and each time a patient opens the cover and breathes through it, the right dose of the powder formulation is dispensed. To sense the user’s breath, the device is equipped with a small vane that moves when the patient breathes, triggering the dispensing mechanisms.
Furthermore, NEXThaler is characterized by a unique audible system: a click is heard as a consequence of the activation of the breath-actuated mechanism, and the dose counter decrements by one count only after the effective release of the dose.
Materials for Functionality
Overall, the aim of the project was to limit the number of materials as much as possible, while still using the material that best met the function of each component.
According to Allen, the components were specified early in the design process based on their functional requirements, including stiffness, friction, dimensional stability, and aesthetics. The requirements led to a set of preferred material types that were selected prior to the first tooling, and have remained unchanged. It hasn’t been necessary to experiment with different materials.
Several engineering plastics were used in the device, including polypropylene, acrylonitrile butadiene styrene (ABS), polycarbonate, cyclic olefin copolymer (COC), acetyl, and polybutylene terephthalate (PBT). Polypropylene is a softer material with tactile benefits but also has good static charge properties. COC provides necessary moisture barrier properties, as the reservoir of powder has to be protected from the environment so the powder won't absorb moisture. ABS provides the hardness required for some components, and also offers good dimensional stability. Using polycarbonate gives the components good dimensional stability, but also hardness and optical clarity. Where low friction was an essential requirement, acetyl, and PBT were specified.
Testing for Reliability
All aspects of the device needed to work reliably, repeatedly, accurately, and required extremely sensitive parts and thorough testing. Thus, the scale up of the device into commercial volumes required a rigorous investigation. “Our approach has included testing the devices across the possible range of manufacturing variations, and then redesigning parts to best deal with these variations,” Allen says.
To make sure the dosing mechanism would be accurate, the team built automated test rigs to simulate a patient using the device, and had them cycle through all 120 doses. “It is incredibly important that the dose counter be fail safe, as it would be dangerous for a patient to have an inhaler displaying an inaccurate number,” Allen explains.
The device is currently approved in Europe and is in the process of seeking FDA approval in the United States.