Aerosol aerodynamic properties

A number of physicochemical properties are associated with aerosol droplets of particles, which impact upon their characteristics as aerosols. The most important of these may be related to the aerodynamic properties of aerosols [6],... 

The special features of the different routes of administration are dealt with in separate sections of this chapter, after a brief summary of the general properties of biological membranes and drug transport, a knowledge of which is important in understanding all absorption processes. It is impossible to be comprehensive in this one chapter, but we will concentrate on factors unique to the routes discussed, such as the properties of the vehicle in topical therapy, and the aerodynamic properties of aerosols in inhalation therapy, to give a flavour of the different problems that face formulators. Where attempts have been made to quantify absorption, equations are presented, but the derivations of most equations have been omitted. 

Chan HK, Gonda I. Aerodynamic properties of elongated particles of cromoglycic acid. J Aerosol Sci 1989, 20, 157-168. 

Aerosol field dynamical studies comprise those investigations of the factors that govern the (spacially) large-scale behavior of the particles. Turbulent transport of particles is the motion of particles in turbulent flow fields. Since the response of a particle to this flow is, by definition, dependent upon its aerodynamic properties, differential motion between particles of differing sizes can greatly influence coagulation and, therefore, the aerosol size distribution. 

K. -H. Naumann, H. Bunz, Aerodynamic properties of fractal aerosol particles. J. Aerosol Sci. 22... 

Equation (1) points to a number of important particle properties. Clearly the particle diameter, by any definition, plays a role in the behavior of the particle. Two other particle properties, density and shape, are of significance. The shape becomes important if particles deviate significantly from sphericity. The majority of pharmaceutical aerosol particles exhibit a high level of rotational symmetry and consequently do not deviate substantially from spherical behavior. The notable exception is that of elongated particles, fibers, or needles, which exhibit shape factors, kp, substantially greater than 1. Density will frequently deviate from unity and must be considered in comparing aerodynamic and equivalent volume diameters. 

A second way to visualize gas behavior is by considering the gas to be a continuous medium, i.e., similar to some sort of interlocking syrup such as molasses or water. Study of medium properties in this case is known as fluid dynamics or for air aerodynamics. In the first case, the microscopic (small) properties of the gas are important. In the second, it is the macroscopic (large) properties which are of interest. Since aerosol particles can span the range from near-molecular sizes up to hundreds of micrometers, the gas in which the particles are suspended must be considered both from a molecular point of view and as a continuous medium. 

We routinely use nose-only inhalation exposure of B(a)P aerosol to evaluate the consequence of prenatal exposure to this toxicant on physiological and behavioral endpoints. The properties of this B(a)P aerosol are shown in Figure 17.4. The aerosol typically exhibits a trimodal distribution with a 93% cumulative mass less than 5.85 pm, 89% cumulative mass less than 10 pm, 55.3% cumulative mass less than 2.5 pm, and 38% less than 1 pm. Fifty-five percent of the aerosol generally has a cumulative mass less than PM2.5 and the mass median aerodynamic diameter (MMAD) + geometric standard deviation for this mode is consistently 1.7 =E 0.085 pm. For several years we employed a rat model exposing timed pregnant dams to inhalation concentrations of 25, 75, and 100 pg/m. ... 

Aerosol properties, such as particle size distribution, aerosol velocity, and hygroscopicity, affect aerosol deposition in the human lungs. Aerosol size distribution, including mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD), is one of the most important variables in governing the site of droplet or particle deposition in the lungs. ... 

Experimental aerosol research frequently requires the controlled generation of an aerosol. A particular property of the aerosol, such as a certain size distribution, may be required to ascertain its transport properties. The control of aerosol generation may extend beyond size distribution and concentration to the physical and chemical properties of the particles. In particular, the effective dose in aerosol therapy is a function of the physical and chemical properties of the aerosol particles in addition to the mass concentration delivered. The size, shape, and structure of the aerosol particles determine their aerodynamic or transport properties and, hence, affect the site and efficiency of deposition. After deposition, these same physical properties of the particles, in addition to the chemical properties, control the surface area of the particles and, hence, the rate of dissolution and absorption of the drug. Consequently, the control of the physical and chemical properties of the aerosol particles and of the number or mass concentration is a prerequisite for the accurate determination of the effective dose in aerosol therapy. 

There are many ways to describe the size of an aerosol particle. For example it may be described by its longest dimension or by a sphere of equivalent volume. It may be described by its light scattering properties or by the way it behaves in an airstream. In a very real sense there is no such thing as the correct size or diameter of an aerosol particle. There are as many correct diameters as there are ways of measuring it, and it is up to the researcher to measure a size parameter relevant to the particular application under investigation. From a deposition perspective, it is the inertial behavior of the particle in an airstream that defines how and where it will deposit (Chap. 2). This characteristic diameter is known as the aerodynamic diameter and is the characteristic diameter that is normally... 

Measurements of the quantity and quality of the aerosolized drug allow characterizing the dosing properties of inhalation devices in vitro. Multistage im-pactors are used to assess particle mass and mass distribntion of an aerosol, and methods are available to estimate the mass median aerodynamic diameter (MMAD) of the aerosol as well as the dose of delivered from and retained within an inhalation system. 

The two main determinants for medicine deposition in the respiratory tract are the aerodynamic size distribution of the aerosol and the manoeuvre with which the aerosol is inhaled. They govern the mechanisms that are respraisible for particle deposition in the lungs. By varying the inhalation manoeuvre, not only the distribution in the airways for the same aerosol is changed in many cases also the amount and properties of the delivered fine particle dose are affected. The complex interplay between inhalation manoeuvre, aerosol properties and site of deposition has led to many misconceptions regarding the best inhaler choice for individual patients and the way these inhalers need to be operated to achieve optimal therapy for the patient. In this chapter the medicine deposition mechanisms for inhaled aerosols are explained as functions of the variables involved. In addition, the working principles of different inhaler types are described and it is discussed how their performance depends on many inhalation variables. Finally, some persistent misconceptions in the literature about the most preferable dry powder inhaler properties and performance are umaveUed. 

The aerodynamic behaviour of aerosol particles depends on their diameter, density and shape. To compare the behavioiu of particles that have different properties with each other, the aerodynamic diameter (Da) has been introduced, which standardises for particle shape and density. By definition the aerodynamic diameter of a particle is the diameter of a sphere with unit density having the same terminal settling velocity as the particle in consideratimi. Only for aqueous droplets with a spherical shape and unit density the aerodynamic diameter equals the geometric diameter. For non-spherical particles, the aerodynamic diameter can be expressed in terms of equivalent volume diameter (De), particle shape factor (x) and particle density (p) (see definitions) Da = De.(p/x)° ... 

Bondietti, E.A., Papastefanou, C., Rangarajan, C. (1987). Aerodynamic size associations of natural radioactivity with ambient aerosols. In Radon and Its Decay Products Occurrence, Properties, and Health Effects. In ACS Symposium Series, vol. 331. American Chemical Society, Washington, DC, pp. 377-397. 

Regardless of the method used to generate the aerosol, efficient pulmonary deposition of the active agent is critically dependent on the aerodynamic diameter of the inhaled particle. Aerodynamic diameter is the physical property of a particle, which defines how it will behave in an airstream, and depends on the particle geometric size, density, and shape. An in-depth discnssion of how particle shape affects aerodynamic diameter is beyond the scope of this review therefore, the cited examples will assume a spherical particle. 

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