Introduction

Inhaled pharmaceutical aerosols cannot act unless they deposit in the respiratory tract. However, the amount and location of such deposition is strongly affected by several factors, including aerosol properties, breath pattern, and lung geometry. Since some control over aerosol properties and breath pattern is possible when designing an inhaled aerosol formulation, access to tools that permit parametric exploration of lung deposition is useful in order to optimize these parameters and guide preclinical development. It is for this reason that methods allowing simulation of deposition in the lung have become increasingly common in the respiratory drug delivery arena.

An example of the kind of information that can be obtained with lung deposition models is given in Fig. 1, where a one-dimensional Lagrangian dynamical model (see later in this chapter for an explanation of this term) is combined with a model of the mucous and periciliary layers to give estimates of drug concentration in the liquid lining the airways when a novel liposomal antimicrobial peptide is delivered as an inhaled aerosol [1]. A similar approach was used by Finlay et al. [2] to guide the development of an inhaled aerosol

Figure 1 Estimated concentrations of liposomally encapsulated peptide (CM3) in the airway surface liquid (ASL) immediately after completion of nebulization for various simulated subject ages, mucus production rates, and tracheal mucous velocities. Generation 0 corresponds to the trachea, while the terminal bronchioles are generation 14. (From Ref. 1, with permission.)

Figure 1 Estimated concentrations of liposomally encapsulated peptide (CM3) in the airway surface liquid (ASL) immediately after completion of nebulization for various simulated subject ages, mucus production rates, and tracheal mucous velocities. Generation 0 corresponds to the trachea, while the terminal bronchioles are generation 14. (From Ref. 1, with permission.)

therapy for the treatment of pulmonary infection and mucous clearance in cystic fibrosis.

Information like that in Fig. 1, and the respiratory tract deposition information that lies behind this data, is increasingly becoming part of the preclinical development process with inhaled pharmaceutical aerosols. The purpose of the present chapter is to briefly outline some of the deposition models that have been used with inhaled pharmaceutical aerosols and their basis. The reader is referred to Finlay [3] for a detailed treatment of the underlying mechanics.

It should be noted that throughout this chapter, the words model and simulation are used to mean a procedure that solves mathematical equations to represent reality. This may be a less common definition of the word model for some readers. However, since the equations governing aerosol and fluid motion are well established and represent reality exactly, such models have the ability to represent reality exactly, at least in principle.

It should be also be mentioned that little attention has been paid to modeling deposition in lungs altered by disease, largely because the geometry of diseased lung airways has not been well characterized and is different for each disease as well as being dependent on the progression of the disease. Application of the approaches discussed in this chapter to diseased lungs is thus largely a topic for future research.

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