AEROSOL DELIVERY APPARATUSThis invention relates generally to aerosol delivery apparatus and more particularly to a type of nebulizer used in such apparatus for administering medicaments in the form of an aerosol.
Respiratory disorders are commonly treated by delivering drugs by inhalation. This is advantageous because the drug is delivered directly to the large surface area of the tracheobronchial tree and alveoli and can begin to act very rapidly. Also because a large proportion of the dose reaches the lungs rather than being diluted in or eliminated from the body, a smaller dose can be used than by ingestion or intravenous delivery. This can, therefore, reduce the incidence of undesirable side effects.
Most drugs delivered by the inhalation route are delivered as an aerosol, i.e. a suspension of solid particles or liquid droplets in a gas, usually air. The behaviour of aerosols in the respiratory tract is governed by the laws of aerosol kinetics and for medical purposes one is principally concerned with how the substance is distributed and deposited. Deposition of the aerosol substance is principally by inertial impaction and gravitational sedimentation. There are other mechanisms, for instance Brownian diffusion, but these are of little relevance to the administration of medicament aerosols.
Inertial impaction occurs chiefly with larger particles whenever the transporting airstream is fast, changing direction, or turbulent (for example, in the oropharynx or at bifurcations between successive airway generations). Inertial deposition therefore is confined mainly to the upper airways, nose, mouth, pharynx, and larynx and large conducting airways of the lung down to 2mm in diameter where the flow rate is high.
Gravitational sedimentation, by contrast, is a time dependent process in which small aerosol particles settle in airways under the effect of gravity, during either breath holding or slow tidal breathing. It takes place mainly in small airways ( < 2mm diameter) and alveoli, where the larger ip cross sectional area gives low flow rates and where large particles will rarely penetrate. This combination of small particles in small airways with low flow rates gives time for the particles to sediment over the short distance required.
The physical property of the aerosol itself which influences the deposition within the respiratory tract is the aerodymamic diameter (the product of physical diameter and the square root of density). As the aerodynamic diameter increases from about 2um, deposition in theoropharynx and large conducting airways becomes more likely, although less aerosol is exhaled and less reaches the most peripheral parts of the lung. Therapeutic aerosols are usually heterodisperse, that is, they comprise particles of many different sizes and their behaviour is probably best described by the mass median aerodynamic diameter (MMAD); half of the aerosol mass is contained in particles smaller and half of the aerosol mass in particles larger than theMMAD.The ideal size profile for a therapeutic aerosol is not known precisely but it seems that the MMAD should be not more than Sum to penetrate into the tracheobroncial tree and smaller airways if peripheral deposition is required.
In general, most aerosol particles greater than 8um diameter will impact above the level of the larynx and will not reach the lung. Particles of 1-8um may be deposited by impaction and sedimentation in both large and small airways and alveoli. Particles less than lum diameter may not be deposited at all, many being respired like an insoluble gas.
Of course, the overlap between particle sizes and area of deposition may be considerable.
One type of prior art delivery device is the air driven jet nebulizer in which a flow of compressed air is used to generate an aerosol which is then inhaled by the patient. For a nebulizer which delivers a liquid aerosol, aerosol size is inversely proportional to the compressed gas flow rate and a flow rate of greater than or equal to 6 litres per minute is necessary with most types of jet nebulizer. This ensures that the bulk of the aerosol mass is contained within particles of not more than 5um aerodynamic diameter. However, with many types of nebulizer only about 10% dose reaches the lungs, most of it being retained as large droplets on the internal walls of the nebulizer itself.It is thought that droplets of less than 5um diameter may comprise the "respirable range" and only those droplets of less than 2um diameter are ideal for penetration to the most peripheral parts of the lungs.
Thus with the present invention the size distribution of the inhaled aerosol from an aerosol delivery system is improved so as to achieve a more efficient penetration of the drugs into the lung.
According to the present invention there is provided an aerosol delivery system including a nebuliser for producing an aerosol, the nebuliser having an outlet duct including deflection means to deflect transversly of the outlet duct, aerosol flowing through the outlet duct, whereby the aerosol is size-selectively filtered.
The apparatus may include a delivery duct out of which the aerosol is delivered, wherein the delivery duct is connected at a junction to the outlet duct from the nebulizer and to at least one other duct, and the deflection means is provided upstream of the said junction with respect to the flow of the aerosol, between the junction and the nebulizer.
The deflection means may comprise a one-way baffle valve and the outlet duct may comprise a substantially straight section communicating with the container a chamber in the nebulizer occupied, in use, by the aerosol and with deflection means positioned within the straight section, conveniently at an end of the straight portion of the outlet duct remote from the chamber.
Thus with the present invention the size distribution of the inhaled aerosol from an aerosol delivery system is improved so as to achieve a more efficient penetration of the drugs into the lung.
The invention will be further described by way of non-limititive example with reference to the accompanying drawing in which the sole figure is a diagrammatic sectional view of a nebulizer embodying the present invention.
As can be seen in the drawing the aerosol delivery apparatus comprises a nebulizer part 1 attached to delivery ducting 3 to carry the aerosol to the patient. The delivery ducting 3 comprises a delivery pipe 4 connected to a mouthpiece 21 and which has two branches 6 and 8 one of which, 6, is open to the atmosphere and is provided to allow a patient to exhale through it and the other of which, 8, is connected to the exit pipe from the nebulizer. While the branch 6 is illustrated as permanently open to the atmosphere, in an alternative embodiment a one-way valve may be provided in it, for instance to prevent any possibility of aerosol escaping to the atmosphere by reverse flow. The nebulizer 1 includes a container 13 which ss#contains the material 11 to be nebulized.Container 13 includes a chamber 19 above the material 11 which chamber communicates via a straight outlet duct 23 with the delivery ducting 3.
A one-way baffle valve 25 is positioned in the outlet duct of the nebulizer between the nebulizer and junction between the outlet duct 23 and delivery ducting 23 at the end of the straight section of the outlet duct.
In order to form the aerosol, air or another compressed gas is supplied through an inlet 5 in the direction of arrow A through a sub-chamber 7 to a venturi 9.
The gas flows through the venturi and this causes a drop in pressure downstream of the venturi. A supply pipe 15 leads from the material 11 to a region adjacent the downstream side of the venturi and the lowering in pressure caused by the flow of gas through the venturi draws the material up the feed pipe into the gas stream. The gas and material pass through an aperture 17 downstream of the venturi and are formed into an aerosol. This aerosol circulates in chamber 19 of the material 11.
The baffle valve 25 in the nebulizer exit pipe is normally closed. However, when the patient sucks on the mouthpiece 21 aerosol flows from chamber 19 past the open baffle valve 25 and into the patient in the direction of arrows C. The baffle valve deflects the flow of the aerosol to some extent and imparts a transverse velocity component to it. Small particles or droplets in the aerosol flow easily around the valve without impacting with it or with the side walls. Larger droplets, however, cannot flow so easily with the deflected air and tend to impact with the valve or wall and flow back into the container 13. Thus larger particles or droplets are selectively filtered out of the aerosol.
The performance of an aerosol delivery system as described has been compared with the performance of a standard nebulizer with no baffle valve or other deflector in the exit pipe. It was found that with the standard nebulizer the percentage mass of droplets of size less than 2um was 39.9% whereas with the present invention 72.8% of the mass was contained in droplets less than 2um in diameter. With the standard nebulizer the mass median diameter was 3.4um whereas with the present invention it was only l.Oum. Also, the maximum droplet size with the standard nebulizer was 25.3um whereas it was only 8um with the present invention. These figures clearly show the advantage in the placement of the baffle valve into the exit duct of the nebulizer and it was found by monitoring the deposition of the substance in the patients lungs that a corresponding improvement in alveolar deposition was obtained.
A particular form of the invention has been described and illustrated above but it will be apparent that various modifications will be made without departing from the spirit and scope of the invention and accordingly it is intended that the invention should not be limited except as by the appended claims.