Effect of poor inhalation-actuation coordination on the deposition of a pMDI drug used in current asthma and COPD therapy

Árpád Farkas¹, Attila Kerekes² & Alpár Horváth^3,4

¹Centre for Energy Research, Konkoly Thege M. 29-33, Budapest, 1121, Hungary

²Wigner Research Centre for Physics, Konkoly Thege M. 29-33, Budapest, 1121, Hungary

³Chiesi Hungary Ltd., Dunavirág u. 2, Budapest, 1138, Hungary

⁴University of Debrecen, Nagyerdei körút 98, Debrecen, 4012, Hungary

Summary

In spite of their numerous advantages, pressurized metered drug inhalers (pMDI) have also a number of drawbacks. Lack of synchronization between the beginning of the inhalation and device triggering is one of the most frequent errors. The aim of this study was to apply experimental and numerical methods to analyse the effect of poor inhalation-actuation coordination on the lung deposition efficiency of a combination drug. A computational fluid and particle dynamics model was combined with a whole lung stochastic model to quantify the amount of drug depositing in the extra-and intrathoracic airways. The numerical model has been validated against experimental measurement data available in the open literature. High speed camera measurements were performed to characterize the emitted spray plume in order to provide input parameter values for the computer model. The computations were performed for 30 L/min steady flow. Our results have shown that near this slow flow rate late actuation leads to reasonable loss in terms of lung dose, unless it happens in the very last phase of the inhalation. According to our computational results, a 50% reduction in lung dose corresponds to a 2.6-2.7 s device actuation delay in case of a 3 s inhalation and to a 4-4.3 s delay in case of a 5 s inhalation. These results suggest that in case of patients who cannot achieve a good synchronization it may be plausible to advise them to trigger the device as rapidly as possible after the beginning of the inhalation rather than forcing a perfect synchronization and risking mishandling and poor drug deposition. Present work is the first step of a more extended study of the effect of delayed pMDI actuation. Simulations for higher flow rates and unsteady flow are planned. Preparations for conducting validating deposition experiments are also in progress.