(752d) A Dry Powder Inhaler, a User Interface or a Formulation Interface? Designing for Quality Amidst Competing Requirements

A dry powder inhaler is the physical interface that sits between the patient and the powder formulation. Faced with the device, the patient must go through a number of steps to prime and prepare the dose, before inhaling on the device. During the inhalation, the patient’s inspiratory energy is used to break up the powder and to deliver the powder to the lungs. Clearly, both the inner workings of the inhaler and the manner in which that inhaler is used have a significant and direct influence on the clinical efficacy of the product. However, this raises two competing design requirements which are often dealt with as separate design activities.

Laboratory testing shows that, when correctly used, the performance variation between different inhalers, and at different flow rates through the same inhaler, is significant. When user error and compliance issues are considered on top of that inherent variability, the need for quality design is abundantly clear. However, true QbD to mitigate this variability is perhaps an unrealistic proposition. Despite this, there remain a wide range of poorly understood factors which are central to the DPI performance where improved understanding and characterisation can bring us a step closer to QbD.

The physics that determines performance is multifaceted and is influenced by turbulence, shear, impaction, entrainment, deaggregation and deposition. Compounding this complexity is a lack of available methods for direct characterisation of these factors. As a result, the DPI airpath is often developed as a consequence of, and not in concert with, usability and mechanical design requirements. This approach effectively prioritises the aspects of the design that can be more readily quantified over and above the aspects of the design that are poorly understood. Instead of improving quality, this design paradigm simply hides the unknowns.

This paper will focus the characterisation of the airflow within the device and on the characterisation of the powder behaviour as a result of that airflow. The analysis will focus on new approaches for both in-silico and in-vitro data analysis that can help to unpick the causal relationships that determine DPI performance. The data also highlights the detrimental influence that competing design requirements of usability and performance can have on the performance and consistency of the product. The presented methods provide a set of tools that can be used to improve the quality of DPI design, and that can be used provide a central focus for disparate design teams.