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 parameter, indicating the need for the whole size distribution when modelling 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.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract

“…In the past decades, two deposition, clearance and radon dosimetry models have been developed on the basis of the original version of the SLM model that include a realistic airway structure. The IDEAL-DOSE code was created at the University of Salzburg, Austria (Hofmann et al 2010), while the SLM-Radact code was developed at the Centre for Energy Research of the Hungarian Academy of Sciences, Hungary (Farkas et al 2015;Füri et al 2017). Although the basic structure of the two deposition models is similar, the Radact code was optimised to simulate the deposition of radon progeny and medical aerosols.…”

Statistical Analysis of Fine Particle Resuspension from Rough Surfaces by Turbulent Flows

“…Turbulence-induced resuspension of fine particles from surfaces is closely related to a variety of applications and phenomena, such as cleaning and preparation of semiconductor surfaces (Lim et al, 2005), dose supply control of dry powder inhaler (Farkas et al, 2015), transport of microorganisms in environments (Jamieson et al, 2005), and spread of radioactive dust related to the operation of a nuclear reactor (Garimella and Deo, 2007). Recently, particle resuspension has gained increasing attention because deposited particles could be an important source for indoor and outdoor airborne particulate matters (PM) and has the potential to prolong human exposure to harmful particles (Munir et al, 2013;You et al, 2013;You and Wan, 2014c;Dimitriou, 2015).…”

Prediction of localized aerosol deposition in a realistic replica of human airways using experimental data and numerical simulation

“…One approach is to use stochastic lung deposition models. This type of simulation has been applied recently by Farkas et al [3] to calculate the deposition distribution of two marketed aerosol drugs. Another approach utilizes the fast development of computational fluid and particle dynamics (CFPD).…”