Computer modelling as a tool in characterization and optimization of aerosol drug delivery

Abstract

The number of patients with obstructive airway disease has been increasing worldwide. The delivery of aerosol drugs through the respiratory system has become a central element in the management of asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to validate and apply a stochastic whole respiratory tract deposition model in order to characterize airway deposition distribution of two different marketed drugs delivered in form of dry powders (Seretide® Diskus® and Symbicort® Turbuhaler®), and to analyze the possibility of computerized drug delivery optimization in the future. Spirometry measurements on 17 adult volunteers have been performed. Relationships between breathing parameters measured during diagnostic spirometry and those characterising breathing during drug administration through Diskus® and Turbuhaler® inhalers have been derived. The doses deposited in different anatomical regions of the respiratory tract and airway generation number specific deposited doses have been computed for the participating individuals based on both mass median aerodynamic diameter (MMAD) and detailed size distribution of the two drugs. Although regional deposited doses were not very different in the two cases, airway generation number specific deposition distributions were sensitive to this input arameter, indicating the need for the whole size distribution when modeling airway deposition of aerosol drugs. Significant intersubject variability in terms of oropharyngeal, bronchial and acinar deposited doses have been found. The results highlight the necessity for and open the possibility of simulation assisted customized drug selection in the future.