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Addressing Inter-patient Variability in Dry Powder Inhalers: Optimizing Powder Entrainment Using Computational Fluid Dynamic-guided Dry Powder Inhaler Design

Murnane D, Kopsch T, Symons DD.

RDD Asia 2018. Volume , 2018: 73-82.

Abstract:

Dry powder inhalers (DPIs) are a popular therapeutic strategy for achieving drug delivery to the lungs. Despite decades of research and clinical use, significant challenges still exist for DPI device design when developing new products. The inter-patient variability in product performance because of differing inhalation maneuvers remains a particular challenge. In this work, a framework for employing computational fluid dynamic (CFD)-guided design optimization of DPI devices is presented. An approach to scale the inhalation flow-volume-time profiles for comparison between different inhalation maneuvers was developed. Employing the scaled inhalation profiles, a CFD approach was used to identify the optimum geometric dimensions of the entrainment chamber components. As a result, the variability in aerosol entrainment when patients breathe with different inhalation volumes and flow rate profiles was minimized. Finally, an approach to design DPIs where the design of the entrainment chamber has already been locked in (e.g., where a platform device technology is employed) was developed. CFD-studies were performed where a bypass airpath in the device was employed to ensure consistent airflow profiles through the entrainment chamber when patients inhale with different inhalation profiles. The optimum ratio of bypass-to-entrainment airflow for individual inhalation maneuvers was identified. As a result, an approach to “personalize” a DPI device for individual patients is proposed. Through CFD-guided design optimization, the appropriate geometric dimensions of the bypass channel component were identified for specific inhalation maneuvers. Therefore, the appropriate bypass chambers could be selected for different patients, ensuring that a consistent airflow is achieved through the entrainment chamber regardless of a patient’s inspiratory function.