Numerical Modeling of Agglomeration and De-agglomeration in Dry Powder Inhalers

Abstract

Effective dry powder inhaler design is very challenging due to the involvement of various factors including the anatomy of airways, physical properties of dry powder, and fluid dynamics of inhaler devices. Computer-aided engineering, such as numerical modeling, is a new approach to solve problems in a complex system. Computational fluid dynamics (CFD) is a powerful method to simulate and analyze fluid flow in a dry power inhaler. It provides in-depth information during aerosolization processes in the inhaler device and particle deposition in the human airways. The aerosolized efficiency depends on inter-particle interactions in the powder and airflow–particle interaction which can be modeled with mathematical equations. The numerical model is used to optimize the dry powder formulation by identifying factors affecting the forces between particles. Meanwhile, the CFD provides flow field and aerodynamic characteristics information about the dry powder inhaler devices and the researcher can run trial and error on the design in silico to maximize the de-agglomeration force that is directly related to fine particle fraction. The CFD can be combined with advanced medical imaging techniques, such as computed tomography and magnetic resonance imaging, to obtain a realistic simulation of particle deposition in lungs. The computational model also provides information to design targeted aerosol therapy and personalized medicine. This chapter covers the basic principles of CFD and application of the numerical method in the device designs, particle deposition in lungs, and pharmacokinetic/pharmacodynamic predictions of dry powder inhalers.