Abstract
Introduction
A novel modelling and simulation approach for improved characterisation of dose-response relationship of inhaled therapeutics was designed and verified using lung delivery of QVA149, a combination of indacaterol (IND) and glycopyrronium (GLY), delivered via the Breezhaler® device.
Methods
Computational fluid dynamics (CFD), with next generation impactor and particle image velocimetry measurements was used to evaluate the effect of particle size distribution, flow rate and batch variability on drug lung delivery.
Results
More drug loss was observed in mouth-throat region at a high flow rate and in capsule/device at lower flow rates resulting in a consistent lung delivery of QVA149 for both active ingredients IND 110µg and GLY 50µg across flow rates of 30-120L/min (figure1a). Similar lung doses of IND 150µg and GLY 50µg were observed when given as monotherapy. Various batches of QVA149 showed similar lung deliveries at 90L/min (figure1b).
Conclusions
Using the CFD model, we showed that the Breezhaler® device produced a consistent lung delivery of QVA149 as well as of GLY and IND across the flow rates (30-120L/min), an important outcome for patients with varying age or COPD severity. Delivery was consistent across the measured batches.
- © 2014 ERS