DPI Performance Modelling Using an Inhalation Simulator and Oropharyngeal Model: A more Patient-Relevant Approach for Device Development.

Daniel James Lock, Adam Watkins, Alexander Munro

The performance of Dry Powder Inhalers (DPIs) is dependent on several factors including device design, formulation properties and the patient’s inspiratory effort (1). Standard in vitro tests for DPIs employ cascade impactors with square-wave inhalation profiles (2), however DPI performance can be affected strongly by both peak inspiratory flow rate (PIFR) and acceleration rate (1,3).

The use of more patient-relevant testing methodologies using Oropharyngeal (OP) models and more realistic inhalation waveforms (4-6) is becoming more common as a consequence of efforts to improve in vivo/in vitro relationships (IVIVR) and to apply Quality by Design (QbD) principles to DPI development. Using an Alberta Idealised Throat (AIT), OP model in conjunction with an inhalation simulator, this study evaluated the aerodynamic particle size distribution of emitted doses from the Breo® ElliptaTM. Using a series of idealised inhalation profiles, a range of pressure drops and acceleration rates were applied in a Design of Experiment (DoE) based approach. Measurements of Fine Particle Mass (FPM), Impactor Sized Mass (ISM) and OP deposition indicated that the aerosolisation and delivery of drug to the impactor varied independently for each formulation and depended on the inhalation profile applied. Of the factors studied, acceleration rate was found to have a significant influence on FPM and ISM whereas the flow rate through the device was found to have no influence.

It is proposed that the methodology described herein can yield an improved description of a DPI product’s performance when tested under more realistic conditions, reflective of the influences brought to bear during actual patient use. Testing orally inhaled pharmaceuticals (OIPs) in this way may better inform QbD approaches to inhaled product development.

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