Inertial Impaction

Inertial impaction has been used to sample and size fractionate aerosol particles and droplets for many years [7,8]. The original devices were designed to sample atmospheric air for pollutants, and many are still used for this purpose [9-18]. The nature of the development of these devices has had some implications for their use by the pharmaceutical scientist. The interest in their theoretical performance and practical application resulted in many of their limitations being understood before their use for characterizing pharmaceutical products. However, they were designed and calibrated to sample aerosol particles over a larger size range than is necessary for therapeutic purposes and, in some cases, under airflow conditions far in excess of physiological conditions (Sierra 23-L, Sierra Instruments, Inc., Carmel Valley, CA) [19]. Complications in data interpretation may arise from the sampling techniques used specifically to assess pharmaceutical aerosols. These are discussed in later sections.

Calibration

Inertial impactors are calibrated using monodisperse aerosols. Generation of monodisperse aerosols is discussed in detail elsewhere in this book (Chap. 8) [20]. The most commonly used methods are the vibrating orifice [21,22] and the spinning disk (or top) [23-25]. The spinning-disk method has the advantage of generating large concentrations of aerosol. The production and removal of secondary droplets [25], necessarily of a different size than the primaries, by the latter method requires close monitoring to ensure that a truly monodisperse aerosol is being generated. The vibrating-orifice generator produces a low-concentration aerosol output. Consequently, calibration can take considerable time. The most significant source of polydispersity in this device is a tendency of the orifice to clog. The experienced investigator can avert this error by monitoring at intervals for deposits. The droplet size may deviate from theoretical expectations when there are any imperfections in the orifice. Microscopic examination before initiation and upon completion of the study should show a perfectly circular orifice. This procedure allows the condition of the orifice to be established over the time frame of the study.

The method of calibration involves investigating each stage independently [26,27]. Monodisperse aerosols of a known particle size may be generated and collected on a single stage. The fraction of the aerosol that is not collected on the stage is collected on a filter to allow estimates of the total mass of aerosol being generated. The filter used for this purpose collects particles 0.2 mm in diameter and larger. The amount deposited on each stage can then be expressed as a percentage of the total collected (stage plus filter). By plotting the percentage collected against the particle size, a sigmoid curve is obtained, as shown in Fig. 1. The middle portion of this curve indicates the 50% cutoff diameter. This is the diameter at which it was determined experimentally that 50% of the particles were collected and that the remaining 50% were passed to the absolute filter. The curve differs from that derived theoretically, which is a step function, with a cutoff diameter indicated by the vertical portion of the curve, also shown in Fig. 1.

Filtration

Filter Holders

Filter holders are required to facilitate sampling and are made by a variety of companies (Millipore, Cambridge, MA; BGI, Waltham, MA). These are usually made of stainless steel, with machined inner surfaces to allow the unperturbed

Figure 1 Hypothetical collection efficiency of a stage of an impactor. Fraction deposited plotted against particle size. The step function indicates the theoretical deposition, and the curve indicates the practical characteristics.

passage of air through the device. Fig. 2 shows a general design of a filter housing. The aerosol inlet (A) is conical to direct the aerosol to the filter. A central mesh (B) supports the filter selected for sampling the aerosol. The outlet is not subject to the same design constraints as the inlet because it does not carry aerosol. Thus, the body of the housing may be reduced to the dimension of the outlet orifice over a short distance (C). Air is drawn through the filter by means of a vacuum pump connected at the outlet. The filter housings may be grounded to prevent electrostatic deposition of charged particles.

Filters

Fiber Filters. Fibers have proven efficient surfaces on which to deposit particles. Glass fiber filters are frequently used as "absolute" filters to collect particles 0.22 mm in diameter and greater. The advantage of fiber filters is their ability to allow the passage of the large volumes of air usually accompanying an aerosol while retaining the particles. As the particle size of the aerosol to be collected increases, the filter required to collect it uses larger-diameter fibers and will allow the passage of larger volumes of air. The operational pressure drop across a fiber filter is relatively small [28].

The principle of filtration combines many of the individual mechanisms of collection on which other methods are based. Thus, diffusion (Brownian motion), inertia, interception, charge, and sedimentation may all contribute to deposition of particles on filters. The inertial and interception effects are illustrated in Fig. 3.

Figure 2 Photograph of a filter holder for aerosol sampling. Disassembled view shows (A) conical inlet, (B) mesh support for filter, and (C) outlet.

A large particle will follow a path deviating from the streamline as it approaches the fiber and will impinge on the fiber surface. If the particle follows a path approximately perpendicular to the fiber surface, it is deposited as a result of its inertia. Those particles that do not follow a path directly to the surface of the fiber but that enter the airstream passing within the distance equivalent to the radius of the particle from the fiber will be intercepted. It is only necessary for the surface of the particle to touch the fiber for capture to take place [29].

The theory of deposition on fibers, or cylinders, lying transverse to the direction of airflow has been studied thoroughly [9,28-32]. Fiber filters have been placed in specialized pharmaceutical aerosol sampling tubes that can

Figure 3 Principle of interception of particles by fibers showing large particles impacting, small particles being intercepted as they pass close to the surface, and the smallest particles passing beyond the fiber.

be used to collect particles emitted from inhalers. Such a device, shown in Fig. 4, is identified in the United States Pharmacopoeia [33,34]. The recommended operating conditions are unique to this device and require a fixed pressure drop (4 kPa) to be generated across the device from which the aerosol is sampled in a fixed volume of 4 L.

Membrane Filters. The cellulose-derivative membrane filters, as we know them, have been available since 1927 and are now commonplace [29,32,35-38]. The classic membrane filters are prepared by means of a colloid chemical process: gelation of concentrated colloidal solutions of polymers and removal of solvent to leave pores. Although porous, in practice they differ from the capillary model of a pore in that their structure is not regular. A classic membrane filter has three different structures: the upper surface structure, the inner structure, and the lower surface structure [29,35-38]. These filters contain tortuous channels, and the pore sizes inside the filter are larger than those on the surface of a membrane filter. The diameters of these channels can be closely controlled during manufacture. The mechanisms involved in the capture of

Figure 4 Emitted dose sampling tube (Nephele). Disassembled view shows (A) rubber mouthpiece for connection to (B) inhaler cylindrical inlet, (C) filter, and (D) outlet through which vacuum is employed to draw air.

particles are diffusion, sieving, and impaction with little influence of charge [28,29]. The pressure drop across these filters is high, and they are usually used at relatively low airflow velocities.

Membrane filters are particularly appropriate for use in conjunction with microscopy because most particles are deposited on the upper surface. This is shown in Fig. 5, which is a scanning of aerosol particles on a membrane filter. High-power light microscopy is also possible, because the filter becomes transparent on the application of immersion oil.

The nucleopore membrane filters are more recent developments, being available since 1965 [35-37]. Nucleopore membrane filters are prepared by means of a nuclear physical process: neutron irradiation in a nuclear reactor followed by chemical etching. The structure of the resulting filters is geometrically regular. The capillary filter model fits a nuclear membrane filter well [38].

Both classic membrane filters and nucleopore membrane filters are made of organic materials soluble in many nonaqueous solvents. Types of metallic membrane filters are also available, for example, silver metal membrane filters. These filters are made by means of a powder metallurgy process. They are useful for organic microanalysis of aerosol samples [39].

The optimal mean filtration radius is an arithmetic average of pore radii measured on the surface of a membrane filter by means of electron microscopy and is used to characterize cellulose, nucleopore, and silver membrane filters.

Figure 5 Scanning electron micrograph of particles deposited on membrane filter.

Collecting aerosol particles on different filters allows particles to be segregated by size. A graded sequence of filters may be used, providing the pressure drop at each stage is monitored.

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