Exploring the impact of sample flowrate on in vitro measurements of metered dose inhaler performance.

Pharmacopoeial methods for measuring the aerodynamic particle size distribution (APSD) of metered dose inhalers (MDIs) specify the application of a 28.3L/min sampling flow rate during testing. However, there is little data within the literature to rationalise this test condition and it may be that it was originally specified on the basis of the measurement capabilities of the Anderson Cascade Impactor (ACI), rather than direct clinical significance1. As MDIs are propellant-driven it has been argued that the size of particles produced should not be affected by test conditions. Furthermore Chapter <601> of the United States Pharmacopoeia (USP) arguably gives the impression that using the ACI at flow rates other than 28.3L/min is unacceptable, and a standard test flow rate has remained in place for many years2. The standard USP induction port (IP) is also deployed routinely for APSD measurement although there is widespread recognition that this fails to accurately reflect deposition behaviour in the upper airway of adults3.

In this article, we present new data from three experimental set-ups that suggest that the assumption that APSD measurements for MDIs are unaffected by sampling flow rate may be flawed. The results highlight the potential to make testing more relevant to clinical practice and outcomes, by modifying test flow rate and induction port choice, where the aim is maximise understanding of the product to support effective development.