Title:
ULTRASONIC NEBULIZER
United States Patent 3812854


Abstract:
A device for the ultrasonic nebulization of liquids. Nebulization takes place in a porous solid body the porosity of which determines the size of the liquid particles generated. The device is especially suitable for nebulizing liquid medicaments for inhalation therapy.



Inventors:
Michaels, Alan S. (Atherton, CA)
Buckles, Richard G. (Menlo Park, CA)
Keller, Michael P. (Mountain View, CA)
Application Number:
05/299194
Publication Date:
05/28/1974
Filing Date:
10/20/1972
Assignee:
MICHAELS A,US
BUCKLES R,US
KELLER M,US
Primary Class:
Other Classes:
239/102.2
International Classes:
A61M15/00; B05B17/06; A61M11/00; (IPC1-7): A61M15/00
Field of Search:
128/194,DIG
View Patent Images:
US Patent References:
3653379ADJUSTABLE PRESSURE IPPB VENTILATOR1972-04-04Glenn
3561444ULTRASONIC DRUG NEBULIZER1971-02-09Boucher
3400892Resonant vibratory apparatus1968-09-10Ensminger
3243122Ultrasonic spray apparatus1966-03-29Snaper
3214101Apparatus for atomizing a liquid1965-10-26Perron
3121534Supersonic liquid atomizer and electronic oscillator therefor1964-02-18Wilson
2949900Sonic liquid sprayer1960-08-23Bodine
2658169Production of aerosols1953-11-03Barret



Primary Examiner:
Gaudet, Richard A.
Assistant Examiner:
Cohen, Lee S.
Attorney, Agent or Firm:
Ciotti, Thomas Mandell Edward Sabatine Paul E. L. L.
Claims:
We claim as our invention

1. An ultrasonic nebulizer for atomizing a liquid medicament comprising in combination:

2. The nebulizer according to claim 1 wherein at least 85 percent of said diameters are in said range.

3. The nebulizer according to claim 1 wherein the sizes of said particles are essentially twice the diameters of said pore openings.

4. The nebulizer according to claim 1 wherein the porous body comprises an internal macroporous layer which permits facile passage of said liquid medicament and an outer porous layer whose exterior surface defines said one end.

5. The nebulizer according to claim 1, said nebulizer being adapted to atomize the liquid medicament for inhalation by a patient and including:

6. An ultrasonic nebulizer for atomizing a liquid according to claim 1 wherein the means for supplying liquid to the pores of the porous solid body comprises means for supplying liquid under pressure to a bore in the antennuator horn, which bore communicates with the pores of the porous solid body.

7. An ultrasonic nebulizer for atomizing a liquid medicament for inhalation by a patient comprising in combination, a cylindrical antennuator horn having a large diameter end and distal therefrom a small diameter end and a passageway extending from the small diameter end coaxially through the horn to an external opening; a porous solid body having external pores of diameter of from 0.5 microns to 5 microns affixed to the small diameter end of the antennuator horn, and having a defined intercommunicating pore structure in communication with the passageway; liquid supply means for supplying the liquid medicament to the external opening of the passageway; vibrating means for vibrating the cylindrical antennuator horn and affixed porous solid body at a frequency of from about 15 Khz to about 100 Khz; and a mouthpiece one end of which communicates with said external pores and the other end of which is adapted to be received within the mouth of the patient.

8. An ultrasonic nebulizer according to claim 7 including an inspiration responsive detector positioned within the airstream in said mouthpiece and operatively interconnected with said liquid supply means and said vibrating means, said detector being adapted to activate the liquid supply means and vibrating means in response to physical changes it detects within said airstream.

Description:
BACKGROUND OF THE INVENTION

1. Field Of The Invention

This invention relates to ultrasonic nebulizers. More particularly, it relates to a device for ultrasonically producing liquid aerosols having controlled particle size. In a preferred embodiment, the invention relates to an improved ultrasonic nebulizer for inhalation therapy.

2. The Prior Art

The art is replete with processes which employ aerosols of liquids. Paints, biocides, personal and home care products, gas chromatography and spectroscopy samples, and inhalable drugs are representative of the many materials which are advantageously employed as aerosols. Most commonly, aerosols are generated by drawing the liquid into a high velocity stream of propellant gas. With the growing awareness of the health hazards posed by many of the known propellants, especially the Freon-type gases, other methods of generating aerosols are receiving increased attention.

It is known that aerosols can be generated ultrasonically. A common form of ultrasonic nebulizer achieves atomization by the disintegration of the "geyser" which is produced in a body of liquid by contacting the liquid with a focused beam of ultrasonic compressed wave energy. Devices of this type have been used, for example, in inhalation therapy (see U.S. Pat. No. 3,561,444 issued Feb. 9, 1971 to Boucher or No. 3,387,607 issued June 11, 1968 to Gauthier et al.) and in sample atomization (see U.S. Pat. No. 3,325,976 issued June 20, 1967 to West). Another known type of ultrasonic nebulizer achieves atomization by dripping the liquid to be dispersed onto a continuously ultrasonically vibrating solid plate which breaks the liquid into a variety of particles. Such a device is shown in U.S. Pat. No. 3,291,122 issued Dec. 13, 1966 to Engstrom et al.

Both of these conventional types of nebulizing devices can effectively continuously produce large volumes of crude aerosol but both have three serious disadvantages when preceise nebulization is desired. First, they do not permit accurate control of the amount of liquid atomized; second, they also require relatively long times (often 1 to 10 seconds) after starting to generate a stable consistent aerosol, and finally, they fail to directly generate an aerosol having uniformly sized particles (so-called monodispersed aerosols).

This last failing is especially serious since it is often necessary or desirable to have a monodispersed aerosol. On a theoretical basis, it has been shown that continuous ultrasonic nebulizers should produce uniform particles related in diameter to the reciprocal of the ultrasonic frequency employed. In practice, however, prior ultrasonic atomizers have produced a variety of extraneous large particles which must be screened, settled or otherwise removed, albeit incompletely, as may be noted in U.S. Pat. No. 3,291,122 and Boucher et al. 26 Annals of Allergy 591 at FIG. 4 (1968). This inability to control particle size has limited the usefulness of conventional ultrasonic nebulizers especially in inhalation treatment of the respiratory system where precise control of particle size is most advantageous and true monodispersed aerosols have been long desired.

The respiratory system comprises a series of decreasing diameter branched tubes, including the mouth, larynx, trachea, bronchi, bronchioli and alveoli. It is known that the point at which an aerosol particle deposits in the respiratory system is a function of particle size; 10+ micron particles are laid down in the mouth and larynx, 6 to 9 micron particles are preferentially deposited in the bronchi, 3 to 6 micron particles are preferentially deposited in the bronchioli, 1 to 3 micron particles are deposited in the alveoli, while particles much smaller than about 1 micron are not retained in the respiratory system by Brownian collision with all walls; most of these particles are exhaled.

Many respiratory diseases affect only one of the areas of the respiratory system: for example, pneumonia and emphysema affect the alveoli, bronchitis affects the bronchioli, asthma affects the bronchi or bronchioli, etc. Since the drugs used to treat these diseases, for example, epinephrine, norepinephrine, prostaglandins, steroids, antibiotics, detergents and the like are often highly potent and/or systemically toxic, it would be of utmost advantage to minimize drug dosage by delivering the drug precisely to the affected area. More precise particle size control than possible heretofore would help minimize extraneous drug applications.

Another way to reduce drug dosage during inhalation therapy would be to deliver the drug as a precisely timed pulse. It has been found that the flow of gas in and out of the respiratory system has essentially plug flow characteristics with the first gas inspired eventually filling the most distant alveoli, the last gas inspired filling only the larynx, etc. Precise delivery of an accurately determined pulse of atomized drug at an accurately determined point during inspiration, thus would result in further control of the location of drug deposit. Prior ultrasonic nebulizers are not suitable for accurate pulsed delivery. These devices often require at least several seconds of tuning to achieve a usable aerosol. When used in pulsed applications, conventional ultrasonic nebulizers rely upon interrupting the transmission of the aerosol by bulky ducts and poorly controllable valves rather than by controlling the aerosol's generation.

OBJECTS OF THE INVENTION

Accordingly, it is an object of the present invention to provide a new and improved nebulizer of the ultrasonic type.

A further object of this invention is to provide an ultrasonic nebulizer which will permit precise control of the amount of liquid nebulized.

A further object of this invention is to provide an ultrasonic nebulizer which will permit control of the size of liquid particles formed.

Another object of this invention is to provide a device for the production of aerosols which may be used with improved efficiency for inhalation therapy or other therapeutic purposes.

Yet another object of this invention is to provide an ultrasonic nebulizer for inhalation therapy which can be controlled to deliver a medicament-containing aerosol in the form of a pulse of particular particle size and amount of medicament; positioned at a particular point in the inspiration cycle.

STATEMENT OF THE INVENTION

It has now been found that the foregoing objects, as well as other objects, advantages, and features which will become apparent from the detailed description to follow, are attained by a nebulizer which includes a porous body having a defined intercommunicating pore structure, an oscillator capable of vibrating the porous body at an ultrasonic frequency and a system for supplying liquid to be nebulized to the pores of the porous body.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, wherein like reference numerals designate like parts:

FIG. 1 is an essentially diagrammatic cross-sectional view of an embodiment of the ultrasonic nebulizer of the invention;

FIG. 2 is an essentially diagrammatic cross-sectional view of another configuration of a nebulizer of the invention, and

FIG. 3 is a cross-sectional view of yet another configuration of the nebulizer of the invention.

DETAILED DESCRIPTION OF THE INVENTION

As illustrated in FIG. 1, an ultrasonic nebulizer 1 embodying the present invention has a porous solid body 11 having a defined fixed intercommunicating pore structure. Solid body 11 is affixed to ultrasonic horn or antennuator 12 which is in turn attached to a suitable piezoelectric crystal or other electro-mechanical transducer 14. Crystal 14 is connected via cable 16 to high frequency signal generator 15 which produces an ultrasonic signal of adequate power to oscillate crystal 14. The frequency generated by generator 15 is very suitably the resonant frequency of crystal 14 or a harmonic thereof. Cable 16, generator 15, crystal 14 and horn 12 in combination cause porous body 11 to vibrate at an ultrasonic frequency. Liquid to be nebulized is forced under pressure from liquid supply 17 through conduit 18 through concentric channel (or bore) 19 in horn 12 to the interconnected pores of porous body 11 which communicate with channel 19. Conduit 18 is attached to horn 12 in a manner which does not interfere with the ultrasonic oscillation of horn 12 and porous body 11. As will be appreciated by those skilled in the art, the embodiment of the invention illustrated in FIG. 1 is much simplified to clearly set out the invention. Details, such as for example a housing for the nebulizer or the method of flexibly attaching crystal 14 to the housing or the exact method of fastening conduit 18 to channel 19, may be supplied by one skilled in the art without departing from the spirit of this invention. Likewise, minor modifications, such as the addition of a capability for cooling crystal 14, may be employed.

In operation, liquid to be nebulized is passed through conduit 18 and channel 19 to porous body 11. The pores of body 11 are intercommunicating, so that liquid can be conducted through solid body 11. Thus the liquid from channel 19 moves to the outer surface of porous body 11 and there is nebulized by the ultrasonic vibration into an aerosol having a particle size distribution which is related to the diameters of the pores of body 11.

In accordance with the present invention, liquids are nebulized to aerosols using an ultrasonically vibrating porous body having a fixed pore structure. Unlike prior ultrasonic nebulizers wherein the size of the particles in the aerosol was determined by the frequency of the ultrasonic vibration, the particle sizes achieved with the instant nebulizers are related to the internal geometry of this porous body. Aerosol particle size is a function of the diameter of the outer surface pores. The relationship of outer pore diameter to particle size is essentially:

Particle diameter = 2 × pore diameter

For example, when a porous body having uniform 10 micron pores is used in the present invention, the aerosol particles which result are uniformly from about 18 to 22 microns in diameter. When a porous body having uniform 4 mircon diameter external surface pores is substituted an aerosol having particles from about 7 to 9 micron in diameter is formed. This particle size to pore diameter relationship appears to hold over the range of body external pore diameters of from about 0.5 micron to about 50 microns.

When a body having pores of a variety of sizes is employed, a multi-sized aerosol is obtained. In the preferred embodiments of this invention, wherein aerosols for inhalation therapy are produced, it is most often preferred to have uniform particle sizes. Bodies having uniform pore diameters in the range of from 0.5 to 5 microns produce aerosols ideal for many inhalation applications. Most specifically, bodies having all or a major proportion of their pores in the range of from 0.5 to 1.5 microns produce aerosols excellent for inhalation treatment of the alveoli, bodies having their pores in the range of from 1.5 to 3 microns produce aerosols well suited for treating the bronchioli, while 3 to 5 micron pore bodies produce aerosols most useful for treating the bronchi. As used herein, a body is defined to have a uniform pore diameter within a range when at least about 75 percent of all its pores fall within the given range. Preferably at least about 85 percent of all the pores fit within the specified range.

The pores of the porous body must be joined into an intercommunicating network since when used in accord with this invention, liquid will be passed from one side of the porous body through to the other side.

To achieve reproducible results, the size of the outer pores of the porous body should be fixed. The material of construction of the porous body is not critical so long as it provides a fixed pore size. Porous ceramic oxides may be used as well as porous glasses and metal frits, compressed porous plastics, and certain filters (e.g., nucleopore). These materials are readily available, being used conventionally as filters and catalyst supports.

The porous body should be relatively thin, generally not more than about 1 or 2 cms thick, preferably from 0.01 to 1 cm thick. Undesirably large amounts of energy are required to force the liquid to be nebulized through thicker bodies.

The porous body may be comprised of several layers, for example an internal macroporous layer, which permits the facile passage of liquid, in combination with an outer layer or skin having the required pore size distribution. Such a material can be made by carefully annealing or firing the surface of a macroporous support or by bonding a thin sheet of microporous ceramic, for example 0.005 cm thick, to a sheet of macroporous ceramic, for example 1 cm thick.

The porous body must be vibrated ultrasonically to produce the desired aerosol. This may be carried out by connecting the body to an ultrasonic vibrator such as, for example, by affixing the body to a piezoelectric ceramic crystal. This connection is preferably made through an antennuator horn, which when correctly matched to the piezoelectric crystal frequency, effeciently transmits the ultrasonic oscillation of the piezoelectric crystal to the porous body and if sized correctly permits the ultrasonic energy to be multiplied and focused in the porous body where nebulization occurs. The size and shape of the antennuator horn 12 is not critical. Ideally, it is sized taking into consideration its material and the velocity of ultrasonic waves therethrough to achieve a harmonic relationship at the frequency employed.

The porous body is attached or affixed to the antennuator horn by a method enabling a tight fit and firm attachment to be achieved. The exact method of affixing the porous body to the antennuator horn, while not critical, must be chosen with care. A tight fit must be achieved. Glueing or soldering can be used so long as the pores of the porous body are not blocked or appreciably obstructed. Clamping or threading the porous body to the antennuator horn are acceptable means of attachment.

The antennuator horn is attached to a piezoelectric ceramic crystal or transducer 14. Piezoelectric crystals and their use as transducers are well known. They may be made of materials such as lead zirconate or titanate, and calcium zironate or titanate, with or without traces of salts, for example yttrium, lanthanum, strontium or cobalt. To permit good electrical contact, they generally are coated on two opposite faces with electrically conducting metallic layers. A high frequency signal generator drives the piezoelectric crystal. This generator is capable of producing a signal having a frequency of from 15.00 kilohertz (Khz) to about 100.00 Khz. The power output required depends upon the amount of liquid being nebulized per unit time and the area and porosity of the porous body. As a general rule, at least 20,000 dyne-cm are needed to nebulize 1 cc of liquid into less than 20 micron particles. Best results are obtained when the power output is from about 1 × 1010 to about 1 × 1014 dyne-cm.

Liquid to be nebulized is supplied to the porous body through channel 19 in antennuator horn 12. Channel 19 is illustrated as coaxial with horn 12. This is not critical. It is essential that channel 19 contact body 11 in a manner that the pores of body 11 can communicate with channel 19 and that liquid passing through channel 19 can pass through the pores to the surface of body 11 and there be nebulized. Liquid is fed to channel 19 under pressure via conduit 17 from liquid supply 16. It is required that the liquid be fed under pressure if a substantial feed rate is to be achieved. The pressure employed will depend on the pore size of body 11, the viscosity of the liquid being fed, etc. Generally, pressure of from 1 to 20 psi are suitable and may be achieved by for example, moving the liquid with pumps, compressed gas cylinders and the like.

A great variety of liquids may be nebulized by an apparatus as illustrated in FIG. 1. Water and aqueous solutions, such as of drugs, herbicides, dilute paints and dyes and the like are suitable, as are non-aqueous liquids and solutions having viscosities not appreciably greater than about 500 centipoises. Viscous liquids, such as heavy oils, generally are not suitable for nebulization with the present apparatus as they tend to clog the porous body. Light organic materials such as lower hydrocarbons, oxyhydrocarbons and liquid halohydrocarbons may be easily nebulized for a variety of uses such as for flame spectrographic analysis and similar scientific investigations. Liquid medicaments, both neat and in aqueous and non-aqueous solutions which meet the above viscosity criteria are very suitably nebulized by the device of this invention.

Medicaments which may be administered to the respiratory tract by the present invention include conventional inhalation therapy substances such as bronchodilator decongestants, for example, epinephrine, isoproterenol, isoetharime and phenylephrine; moistening thinning and detergent solutions such as superinone; mucolytic agents such as acetylcystune and enzymes, for example pancreatic enzyme; and water or saline humidity.

Turning now to FIG. 2, a diagrammatic illustration is given of an embodiment of the nebulizer of this invention adapted for use as an inhaler for inhalation therapy. The principle components of this inhaler (inhaler 2) are the same as those of the nebulizer of FIG. 1, including porous body 11, antennuator horn 12, piezoelectric crystal 14, signal generator 15, cable 16 and liquid supply system 17, here shown as a pressure canister; connected to channel 19 via conduit 18. Inhaler 2 also has, in combination with the foregoing components, a mouthpiece 20 adapted at one end to fit the patient's mouth and to admit air as well as medicament through its other end as illustrated, as well as means for automatically controlling the nebulizer during the respiration cycle. This automatic control includes an inspiration responsive detector 21, positioned in the airstream of mouthpiece 20, which reacts to changes in the velocity or pressure of the airstream within mouthpiece 20 thus signalling the commencement of inspiration to control 24 via means 22. Control 24 then opens valve 25 via line 26 and admits the desired amount of medicament from supply pressure canister 17, to line 18, channel 19 and porous body 11. Control 24 also turns on, via line 27, high frequency generator 15 which activates piezoelectric crystal 14 which ultrasonically vibrates horn 12 and attached porous body 11 to nebulize precisely the amount of medicament desired. Inhalation detector 21 and controller 24 may be set to deliver medicament throughout the inspiration cycle or in an especially advantageous mode of operation may be set to order a short burst (say from 0.1 to 1 second) of medication at a preset point during inspiration. This point may be based on the length of time from the start of inspiration or more preferably may be based on the volume of gas inspired. The volume may be simply derived by detecting and integrating the inspiration velocity. The nebulizer of this invention can produce a stable cosistant aerosol of uniform particle size essentially instantaneously, for example, within about 2 milliseconds. Thus it is possible to precisely insert a burst of aerosolized medicament at any desired point in the inspiration cycle and therefore achieve much improved control of inhalation medicament delivery.

Although these constructional details are not illustrated, the inhaler of FIG. 2 can be constructed suitable for stationary or portable use. Because of the excellent direct control of particle size and amount of medicament nebulized, possible with the present invention, bulky filters, classifiers and the like are not required. Also, the electrical power demands of the inhaler of FIG. 2 are modest. Thus it can be constructed, if desired, to be battery operated in a highly portable form.

Turning now to FIG. 3, an embodiment of the invention, atomizer 3, suitable for generating bulk inhalation aerosols or for nebulizing liquid chemical samples for spectrographic or chromatographic analysis is shown. Atomizer 3 is similar to the embodiments of FIGS. 1 and 2 and includes porous body 11, which is here illustrated, not to scale, as a two layer body having a thin (0.05 cm) outer layer having the pore geometry which will give the particle size distribution desired the thicker (0.5 cm) inner layer having a macroporous structure adapted for the facile passage of liquid to be nebulized. Porous body 11 is attached to antennuator horn 12 by means of threaded compression collar 29. Horn 12 is attached to piezoelectric crystal 14 which is driven by ultrasonic oscillations generated by high frequency generator 15 and transmitted via cable 16. Liquid to be nebulized, for example water, is supplied under pressure by liquid supply 17 and line 18 to channel 19 on horn 12. Channel 19 is branched at its upper end where it contacts body 11. This facilitates the more ready passage and even distribution of liquid into body 11. The atomizer is mounted in housing 30, which is essentially sealed except for carrier gas inlet 31 and outlet 32. In operation, carrier gas, which for inhalation uses is usually air or oxygen containing a blend of gasses and for sample atomization is usually a non-interfering gas such as helium or nitrogen, is passed into housing 30 in inlet 31. A mixture of nebulized liquid and carrier gas is then withdrawn via outlet 32 and used as intended by means not shown.

The following examples are merely illustrative of the present invention and are not to be considered as limiting the scope of the invention in any way.

EXAMPLE 1

An ultrasonic nebulizer, substantially as shown in FIG. 1, is constructed. As porous body 11 is employed a 0.1 cm thick, 0.5 cm diameter disc of porous ceramic (aluminum oxide), having a relatively uniform porosity (some pores are as large as 10 or 12 microns, some are as small as about 4 microns) and a mean pore diameter of 6 microns. This body is glued on horn 12, care being taken to avoid blocking the pores of body 11. Antennuator horn 12 is constructed from brass and has the following dimensions: length, 3.12 inches, large diameter 0.45 inches, small diameter 0.20 inches. Channel 19 is coaxially bored in horn 12 and it has a diameter of 0.025 inches. A 0.50 inch piezoelectric ceramic is used as crystal 14. A Hewlett-Packard signal generator and McIntosh 2100 Amplifier having a power output of 205 watts is employed as generator 15. Channel 19 is connected to a Harvard infusion pump. In operation, a 30.00 kilohertz oscillation of 18.2 watts power is applied to antennuator horn 12 and porous body 11. Water is pumped to porous body 11 at 20 psi pressure. The water nebulizes and is emitted from body 11 as an aerosol having particle diameters of from about 8 to about 20 microns corresponding to two times the diameter of the pores of body 11.

EXAMPLE 2

The experiment of Example 1 is repeated with one modification. As porous body 11 is employed a similarly sized disc of porous ceramic having a mean pore diameter of 10 microns. The aerosol produced in this experiment has an average particle size of about 20 microns.

EXAMPLE 3

The experiment of Example 1 is repeated with one modification. The antennuator horn having an internal bore and a porous ceramic tip is replaced with a solid horn having no ceramic tip. Liquid is fed to the end of the horn via an external 0.040 inch diameter tube and a Harvard Positive Displacement pump, operated at 10 psi. An ultrasonic frequency varying from 25 KHz to 100 KHz is applied, with energies of from 150 × 107 - 400 × 107 dyne-cm. Throughout these ranges of frequencies and energies only randomly sized 10 - 70 micron particles of liquid are formed.

EXAMPLE 4

A series of experiments in accord with the experiment of Example 1 are conducted. In three experiments the liquid flow rate is varied from 0.0817 μl/sec to 0.417 μl/sec. The power requirement changes from 29 watts to 18 watts as the liquid feed is decreased. (all at 30 KHz). The particle size of the resulting aerosol remains constant -- averaging 15 microns.

In three additional experiments the glued porous body is replaced by a body of the same material attached by a threaded brass collar. Because of the resulting change in horn mass a new frequency (28 KHz) is found to be optimum. The aerosol particle sizes are the same as in the first three experiments. The power requirements at similar flow rates are reduced to form 18 to 11 watts.

EXAMPLE 5

a. An inhaler substantially in accord with FIG. 2 is constructed. As liquid is employed a solution of medicament comprising epinephrine in distilled water. Controller 24 is set to order nebulization of medicament throughout the inspiration cycle. As porous b0dy 11 is employed a glass frit having a uniform pore diameter of 5 to 6 microns. A patient inhales through mouthpiece 20. This flow of air is noted by detector 21. Controller 24, responding to the signal of detector 21, then opens valve 25 and energizes high frequency generator 15 which in turn actuates crystal 14 which vibrates horn 12 and porous body 11. The medicament is nebulized into an aerosol having 10 to 12 micron particles which is inspired by the subject. These particles preferentially deposit on the throat and larynx of a patient employing the inhaler.

b. The experiment of part (a) is repeated using a 3 to 5 micron pore size glass frit. An aerosol having 6 to 10 micron particles is formed. This aerosol deposits preferentially in an inhaling patient's bronchi.

c. Similarly, when a 1 to 2 micron frit is used, a 2 to 4 micron aerosol is formed, which deposits preferentially in a patient's alveoli.

d. The experiment of part (c) is repeated with one change. Controller 24 is set to deliver only a short pulse of aerosol positioned at the initial portion of the inspiration cycle. In this case, the particles of medicament travel to and are primarily deposited in the most distant alveoli.

EXAMPLE 6

A sample of lower ketones is to be analyzed by flame photometric detector gas chromatograph. An aerosolizer in accord with FIG. 3 is constructed using a bilayer ceramic porous body, the outer layer having an average pore diameter of 2 microns, the inner having a 30 mircon average pore diameter. The mixed ketones are fed to the porous body, a suitable ultrasonic frequency is applied and a suitable carrier gas is fed via inlet 31. An aerosol of ketone is produced by the nebulizer and is carried therefrom by a carrier gas through the chromatograph to a flame photometeric detector where it is analyzed.