Delivering drug to the deep lung

How do you optimize the performance of a capsule dry powder inhaler (DPI) to increase fine particle drug delivery to the deep lung? Using computational fluid dynamics (CFD), we simulated the complex airflow and powder dispersion within a DPI in order to identify key design changes for a next-generation prototype.

The result was a novel DPI concept that allows patients to receive a more consistent dose regardless of how strongly they inhale, helping to improve condition management across different patient groups.

Drug delivery | Mechanical engineering | Device testing

The challenges of dose powder delivery

Fine particle delivery is a key performance metric for the therapeutic effectiveness of a DPI. This is because dose powder delivered by a DPI must be dispersed into respirable particles that are small enough to successfully reach the patient’s deep lung.

Capsule DPIs are often a good option for respiratory drug delivery of powder formulations, particularly for brand-new, innovative drugs that need an efficient route to clinical trials. However, capsule DPIs can also face challenges related to variable fine particle aerosol performance, resulting in patients receiving a low dose if they don’t inhale strongly enough.

Simulating powder dispersion in a DPI

To develop a novel capsule DPI design capable of meeting this challenge, we needed an effective way to simulate powder dispersion within the device. The complex fluid dynamics of powder dispersion within a DPI can be challenging to simulate directly, due to the vast number of turbulent airflow-to-particle and particle-to-particle interactions. To address this, our medical device engineers used CFD simulations to develop a deep understanding of the device flow physics.

Drawing on the CFD simulations to optimize the design of the capsule DPI, Team developed a novel prototype capable of addressing the challenge of variable dose delivery performance. The aim was to improve the consistency of the dose reaching the deep lung, despite the expected wide range of different inhalation efforts used by patients to energize the device.

The novel DPI harnesses a high proportion of inhalation energy for powder deagglomeration, employing a bespoke deagglomerating swirl chamber downstream of the powder exiting the capsule. It also includes a flow straightener at the outlet of the device to reduce the swirl of particles leaving the device, which could otherwise cause detrimental side effects to the patient related to drug deposition in the mouth and throat.
Stuart Abercrombie, Senior Engineering Specialist, Team

Balancing Computational Fluid Dynamics simulation complexity

During the CFD approach, we focused on striking the necessary balance between simulation complexity and flexibility. It was essential for the CFD simulations to be sufficiently accurate to provide valuable industrial design insights, while also remaining flexible enough to support fast-paced design changes.

To achieve this, we started simple and only increased the CFD complexity where needed, until the simulations demonstrated good agreement with the controlled environment room testing of physical prototypes. From here, we were able to rapidly iterate and optimize the design, using CFD to improve our understanding and calculations of the key performance metrics. This led to significant design improvements, along with faster and cheaper development timelines compared to only building and testing prototypes.

Tight budgets and timelines often demand lean and flexible CFD simulations to support device development. It’s an important skill for CFD engineers to make pertinent decisions around simulation strategy, to deliver accurate and insightful results quickly to the project team.
Stuart Abercrombie, Senior Engineering Specialist, Team

Correlating simulations with physical testing

To correlate the CFD simulations, our device testing experts also tested physical prototypes using a next-generation impactor (NGI) to measure the aerodynamic particle size distribution (APSD) of the delivered dose. The test results showed significant improvement of fine particle dose (FPD) and fine particle fraction (FPF). These results correlated with key CFD metrics of greater swirl intensity in the airflow and greater deagglomeration forces acting on the dose particles.

The new design achieved favorable flow rate independence for respirable fraction across a wide range of patient inhalation efforts, from 2kPa to 6kPa pressure drop. The results across this pressure drop range demonstrated stable FPD from 39% to 40%, and FPF from 52% to 57%. This showed that the device could compensate for weak inhalation effort from patients while still maintaining consistent dose delivery.

Outcome

Using CFD, our device engineers were able to rapidly progress the DPI concept development. The novel capsule inhaler improves the reliability of drug delivery by minimizing the impact of variability across patient inhalation capabilities and techniques, drastically improving the consistency of drug delivery to the deep lung.

The novel concept offers a highly beneficial solution for patients to manage their condition effectively, reducing the risk of disease exacerbations and decreasing adverse side effects from drug deposition in the mouth and throat.