WO2025166083A1 - Multi-stage droplet reduction delivery device - Google Patents

Abstract

A droplet delivery device includes an ejector plate the produces a stream of droplets having a first large droplet size from a liquid supplied to the ejector plate and an impingement member that is positioned perpendicular to or at another non-parallel angle relative to an initial aerosol stream path produced from the ejector plate such that the one or more impingement members impinge the aerosol stream and reduce the size of droplets from the first larger size to one or more smaller droplet sizes.

Description

MULTI-STAGE DROPLET REDUCTION DELIVERY DEVICE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application Nos. 63/626,843 filed January 30, 2024, and 63/699,660 filed September 26, 2024, all of which are incorporated herein by reference in their entireties.

FIELD OF THE INVENTION

[0002] This disclosure relates to droplet delivery devices and more specifically to droplet delivery devices for the delivery of fluids that are inhaled into mouth, throat, nose, and/or lungs.

BACKGROUND OF THE INVENTION

[0003] The present application incorporates herein by reference in their entirety the contents of WO 2020/264501 (describing “Ring Mode” ejection), PCT/US2022/034552 (describing “Push Mode” ejection), US Pat. No. 9,956,360 (describing inertial filtering) and W02020/072478 (describing droplet delivery of low surface tension compositions). This application also incorporates herein by reference it their entirety U.S. Provisional Application Nos. 63/626,843.

[0004] There is a need for improved efficiency, including better energy efficiency, and generation of very small droplet sizes created from fluid compositions with droplet delivery devices. U.S. Patent Application Publication No. 2008/0283048 to Petersen (Petersen "048) entitled “Two-Stage Reduction of Aerosol Droplet Size,” incorporated herein by reference in its entirety, discloses a device using a combination of pressurized gas and liquid to create an aerosol in a first stage and then contacting the aerosol with piezoelectric plates in a second stage. Petersen "048 teaches that the plates are aligned parallel in the same direction of the flow path of the aerosol stream, i.e., aerosolized droplets carried by the pressurized gas contact the plates aligned flat in the same flow direction as the stream. The oscillation of the piezoelectric plates is suggested to cause the aerosolized droplets to further nebulize and reduce the size of the droplets. However, the teachings of Petersen "048 that rely on pressurized gas through multiple lumens to propel aerosolized droplets and the parallel and co-directional alignment of the piezoelectric plates with the flow direction of the droplets stream present inefficiencies and unpredictable results for further reducing the droplet size. SUMMARY OF THE INVENTION

[0005] Accordingly, it is an object of the present invention to provide for more efficient reduction of the droplet sizes of fluid compositions ejected from droplet delivery devices through a multi-stage droplet size reduction. In embodiments, an ejector plate of a droplet delivery device produces aerosolized droplets having a first larger droplet size and a subsequent vibrating impingement surface, such as an oscillating plate made of piezoelectric material (piezo) and either including or not including apertures, is aligned to impinge the flow of the droplets stream, such as in perpendicular or angled alignment relating to the aerosol stream produced from the ejector plate, to impede and contact the aerosol stream having first larger droplet sizes so that such droplets that contact the vibrating impingement surface are broken up into second smaller droplet sizes.

[0006] In various embodiments, multiple vibrating impingement surfaces could be provided, such as more than one downstream vibrating plate, to provide multi-stage reduction from larger to increasingly smaller droplet size. For example, two or more downstream vibrating plates could be provided in the flow pathway of the droplet device so that a first larger droplet size is reduced to a second smaller size droplet upon contact with a first vibrating plate, and then the second smaller size droplet is reduced to a third even smaller size droplet upon contacting a second vibrating plate and so forth.

[0007] In another embodiment of the invention, a droplet delivery device with multistage reduction of droplet sizes does not include connection to and supply of pressurized gas in combination with an aerosolized stream of droplets. Instead, a user inhales by mouth or nose at an opening cooperating with an airflow' channel to cause the aerosolized droplet stream to flow through the device and contact the one or more vibrating surfaces to reduce the droplet sizes of droplets in the stream and ultimately pull the aerosolized stream of reduced-size droplets into the user’s pulmonary system.

[0008] In one embodiment, an ejector, comprising a piezoelectric transducer and an ejection plate, aerosolizes liquid in which larger droplets impinge on a vibrating plate. Having less inertia, the smaller droplets will flow around the vibrating plate. The vibrating plate breaks up the larger droplets into smaller droplets. The total aerosol ejection consists of smaller droplets. The vibrating plate can be placed at varying distances from the ejector (e.g., 5mm, 10mm, 15mm, etc.)

[0009] In one embodiment, the vibrating impingement surface is a plate that is a piezoelectric transducer. [0010] In another embodiment, the vibrating impingement surface is a plate that is a surface acoustic wave (SAW) device.

[0011] In one embodiment, there is a current limiting circuit connected to the vibrating impingement surface, such as an impingement plate, to ensure the current does not spike, i.e., when there is no liquid on the plate.

[0012] In another embodiment, the vibrating impingement surface is driven with a duty cycle. This can be used to keep the heating, power, and current low.

[0013] In another embodiment, the vibrating impingement surface and ejector are driven at separate times.

[0014] In another embodiment the vibrating impingement surface is smaller or larger in diameter and/or thickness.

[0015] In another embodiment, there is a second vibrating impingement surface to break up any additional large droplets after an earlier impingement reduction stage into smaller droplets.

[0016] In another embodiment, the second vibrating surface is a cylindrical vibrator (this could also be the primary vibrating plate), such as a piezo tube or piezo cylinder that is hollow like a tube. The aerosol from the ejector (and potentially from any upstream impingement member droplet size reduction stage) flows through the tube, and any larger droplets are broken up by the vibrating tube walls when they fall out.

[0017] In another embodiment, there is a series of vibrating impingement surfaces to continuously break up the droplets into smaller and smaller droplets as multi-stage droplet size reduction process and corresponding device.

[0018] In one embodiment, there is a static plate with small apertures/holes before a second vibrating plate. This plate with small holes increases the velocity of the droplets, causing them to impact on the second plate.

[0019] In one embodiment, a vibrating impingement surface is perpendicular (90^o) to the aerosol flow path.

[0020] In another embodiment, the vibrating impingement surface is positioned at an acute angle to the direction of the aerosol path, i.e., such as including 75°. 60°, 45°. 30°, 15°, 10°’ (impinging the aerosol stream at less than 90°’ but more than 0⁰⁾. In another embodiment the vibrating impingement surface is positioned at an obtuse angle to the aerosol path, i.e., 95°, 100°, 110°, 130°, 145°, 160° (such as impinging the aerosol stream at more than 90°- but less than 180 ^o).

[0021] In one embodiment, push mode is used as the ejector. [0022] In another embodiment, a ring piezoelectric transducer is used as the ejector.

[0023] In another embodiment, some other form of ejector is used.

[0024] In another embodiment, the ejector is propellent based.

[0025] In another embodiment, a jet nebulizer is used as the ejector.

[0026] In another embodiment, the ej ector comprises a primary⁷ vibrating plate to which liquid is placed on top to vibrate off. The liquid is placed on top by wicks, microfluidic pumps, tesla valves or anything thereof.

[0027] In one embodiment, the ejector includes an ejector plate made from a polymer (e.g., polyimide, FEP, polysulfone, etc.) or a metal (e.g., nickel palladium, etc.).

[0028] In one embodiment, the vibrating impingement surface has a frequency of 20kHz to 20MHz.

[0029] In one embodiment, the ejector and vibrating surface are parallel with the airflow (100) while the vibrating impingement surface is perpendicular to the aerosol flow path. [0030] In another embodiment, the ejector and vibrating impingement surface are perpendicular with the airflow (100) and also perpendicular to the aerosol flow path.

[0031] In one embodiment, the airflow (100) surrounds the ejector, flowing with the ejection path.

[0032] In another embodiment, the airflow (100) comes in from one location and flows across the ejector and vibrating impingement surface.

[0033] In another embodiment, the airflow (100) flows around the ejector and vibrating impingement surface(s) is at an angle to the ejector, i.e., 75°, 60°, 45°, 30°, 15°, 10°.

[0034] In another embodiment, a jet aerosolizer sprays onto a vibrating surface that is perpendicular or at an angle to the spray.

[0035] In another embodiment, the vibrating impingement surface is laminated by a plastic that could be hydrophobic or hydrophilic.

[0036] In another embodiment, the vibrating impingement surface is coated with a hydrophobic coating.

[0037] In another embodiment, the vibrating impingement surface is coated with a hydrophilic coating.

[0038] In another embodiment, there is a Peltier device on the vibrating impingement surface to act as a cooling system.

[0039] In another embodiment, the vibrating impingement surface is laminated and submerged in a fluid to act as a cooling system. [0040] In another embodiment, the vibrating impingement surface is not rigid, like lower modulus.

[0041] In another embodiment, the vibrating impingement surface is suspended.

[0042] In another embodiment, the vibrating impingement surface can be square, circular, ring shaped, or any polygon to create different eigenmodes.

[0043] In another embodiment, the vibrating impingement surface is vibrated by a ring piezoelectric material.

[0044] In another embodiment, a gel, paste, or metal part is in contact with the vibrating impingement surface to pull heat away.

[0045] In another embodiment, an ejector plate produces large droplets (e.g., > 5 pm, > 10 pm, > 20 pm, > 30 pm, > 50, > 60 pm and other droplet sizes considered above the respirable range). In embodiments, multi-stage reduction of large droplets from a first stage ejection followed by contact with an impingement with one or more vibrating impingement elements to reduce the large droplets to smaller droplet sizes that preferably result in smaller droplet sizes of less than or equal to 5 pm, and more preferably less than 3 pm (and potentially to less than 2 pm) for the droplets to reach deeper into the pulmonary system since such droplet sizes are within respirable range size, requires less power than push mode, ring mode and other known droplet ejection mechanisms. Further, the improved small size of droplets achieved by multi-stage reduction of the invention can help avoid caustic or unpleasant feelings of an inhaled aerosolized liquid droplets having larger sizes, including ni cotine-containing, alcohol- containing or certain pharmaceutical/therapeutic compositions.

[0046] In another embodiment, the vibrating impingement surface is bonded to another fixed plate to limit the vibrations, heat, and the like.

[0047] In one embodiment, the walls of a vibrating impingement tube have a hydrophobic or hydrophilic treatment.

[0048] In one embodiment, an impingement tube curves after a vibrating impingement surface to provide a static inertial filter.

[0049] In one embodiment, the vibrating impingement surface, is an impingement plate or an impingement transducer with a horn having a contact face, and does not include apertures. In such embodiments, an aerosol stream ejected from an ejector element, such as a ring mode or push mode ejector, contact the impingement surface with larger size droplets that are broken down into smaller size droplets, whereby the smaller size droplets flow around the impingement surface. In alternative embodiments the impingement surface does not vibrate. [0050] In one embodiment, a vibrating impingement plate includes apertures (like a mesh or ejector plate with holes) to allow droplets having a sufficiently small size to go through the vibrating impingement plate. In alternative embodiments the impingement plate does not vibrate, but still “filters” the aerosol stream by smaller droplet sizes that are able to pass through the apertures.

[0051] In one embodiment, a vibrating impingement surface is connected to the piezo that causes the primary ejection. The vibrating impingement surface is not a piezo and does not have its own piezo in this embodiment. This means only one piezo is used to create both vibrations. The vibrating impingement surface would be connected via a rod, or some other mechanism.

[0052] In one embodiment, the vibrating impingement surface is a cone without a top. The aerosol flows through the cone and out the hole at the end. The droplets bump into the edge as it exits thereby decreasing the droplet sizes.

[0053] In another embodiment, the vibrating impingement surface is a dome or cup or hemisphere or high intensity focused ultrasound (HIFU) or some other part of a sphere. The partial sphere may or may not have a hole at its apex.

[0054] In one embodiment, the impingement surface is not vibrating but rather just heated. The heater is controlled electronically to keep it below a temperature that would result in undesirable degradation (such as resulting in toxic or unhealthy chemical components or residue) of compositions being aerosolized for administered treatments. It will be appreciated that the temperature to be monitored and controlled for avoiding such degradation will depend on the type of composition. In some embodiments the temperature of the heatable impingement plate will be maintained below around 80 degrees Celsius, or below around 70 degrees Celsius, or below around 60 degrees Celsius, or below around 50 degrees Celsius. It will be appreciated that the temperature can be controlled via a temperature sensor and controlling the power and electrical resistance of the impingement surface to stay below the target temperature that would result in degradation. The large droplets would impinge on the plate and then evaporate off leaving no residual. The smaller droplets flow around the surface. [0055] In one embodiment, instead of a vibrating impingement surface, speaker(s) or ultrasound generator(s) is placed around the ejector tilted inwards. The ultrasound generator(s) would point at a point in the aerosol path. These would vibrate and create waves in the air. The waves in the air bombard the aerosol causing the droplets to break up into smaller droplets.

[0056] In another embodiment, an ultrasound generator is used to help guide the droplets using the waves through the air. [0057] In another embodiment, the vibrating impingement surface is connected to a knob on the exterior of the device. The user can control the vibrating impingement surface distance from the ejector. Smaller droplets will impinge on the plate when it is closer to the ejector causing a lower MMAD. The further the plate is from the ejector, the larger the MMAD of the aerosol. Higher MMAD provides more throat feel, smaller MMAD provides less throat feel.

[0058] In one embodiment the vibrating impingement surface is a piezo fan. A thin foil is attached to the side of a piezo and the piezo causes the foil to flap back and forth like a fan or flag.

BRIEF DESCRIPTION OF THE DRAWINGS

[0059] FIG. 1 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a downstream vibrating impingement member (10) with a horn positioned perpendicular to the aerosol stream of a droplet delivery device according to one embodiment of the present invention.

[0060] FIG. 2 illustrates a cross-sectional side plan view of a vibrating ejection member

(4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a downstream perpendicularly -positioned vibrating impingement plate

(5) of a droplet delivery device according to one embodiment of the present invention.

[0061] FIG. 3 illustrates a cross-sectional side plan view of a vibrating ejection member

(4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a downstream perpendicularly -positioned vibrating impingement plate

(5) that is larger than the impingement plate shown in FIG. 2 to direct airflow (100) and aerosol stream outward toward the walls of the airflow channel of a droplet delivery device according to one embodiment of the present invention.

[0062] FIG. 4 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a downstream angled-positioned vibrating impingement plate (5) of a droplet delivery device according to one embodiment of the present invention.

[0063] FIG. 5 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a downstream first vibrating impingement plate (5), followed by a static plate with apertures (7) that permit passage of droplets that have a size that can pass through the apertures and a second vibrating impingement plate (5) of a droplet delivery device according to one embodiment of the present invention.

[0064] FIG. 6 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a vibrating impingement plate (5) having apertures that permit smaller size droplets to pass through such apertures, followed by a cylindrical vibrating member (6) (hollow like a tube) that permits passage of droplets passing there through whereby large droplets passing into the cylindrical vibrating member impinge on the inner walls of the cylindrical member in a droplet delivery device according to one embodiment of the present invention.

[0065] FIG. 7 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a vibrating impingement member (10) with a hom positioned at an angle to the aerosol stream of a droplet delivery device, and with airflow (100) in an angular direction between the vibrating ejection member and vibrating impingement member, according to one embodiment of the present invention.

[0066] FIG. 8 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) that is a wall of an airflow channel (13) to direct an aerosol stream (200) across the airflow channel to a vibrating impingement member (10) coupled to a wall of the airflow chamber of a droplet delivery device, and with airflow (100) in a perpendicular direction relative to the aerosol stream direction betw een the vibrating ejection member and vibrating impingement member, according to one embodiment of the present invention.

[0067] FIG. 9 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection along a wall of an airflow channel (13) to direct an aerosol stream (200) across the airflow channel to a vibrating impingement plate (5) coupled along a wall of the airflow chamber of a droplet delivery' device, and with airflow (100) in a perpendicular direction relative to the aerosol stream direction between the election plate and vibrating impingement plate, according to one embodiment of the present invention.

[0068] FIG. 10 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection to direct an aerosol stream (200) to a vibrating impingement plate (5) positioned at an angle to the aerosol stream of a droplet delivery device, and with airflow (100) in an angular direction between the vibrating ejection plate and vibrating impingement plate, according to one embodiment of the present invention.

[0069] FIG. 11 illustrates a cross-sectional side plan view of a vibrating ejection member (4) coupled to a membrane (3) and ejector plate (2) using push mode ejection positioned to direct an aerosol stream (200) to a vibrating impingement member (10) centrally positioned with an impingement face situated perpendicular to the direction of the aerosol stream produced from the ejector plate, wherein airflow (100) in vents are also illustrated in the droplet delivery' device, according to one embodiment of the present invention.

[0070] FIG. 12A illustrates a cross-sectional side plan view of a droplet delivery' device including a vibrating impingement plate (5), such as a vibrating plate or a non-vibrating plate with heating, and airflow (100) is via a single airflow path in one embodiment of the invention. [0071] FIG. 12B illustrates a cross-sectional side plan view of a droplet delivery device including a vibrating impingement plate (5), such as a vibrating plate or a non-vibrating plate with heating, and airflow (100) is via a single airflow path in one embodiment of the invention. [0072] FIG. 13 is a schematic diagram of a droplet delivery’ device including a vibrating plate that does not vibrate on its own but is connected, via a rod or similar attachment and support structure (8), to the vibrating member (such as a transducer or piezo element) that is driving the ejector in one embodiment of the invention.

[0073] FIG. 14 illustrates a cross-sectional side plan view of a droplet delivery device including a cone-shaped piezoelectric transducer (14) for the airflow channel (13) in one embodiment of the invention.

[0074] FIG. 15 illustrates a cross-sectional side plan view of a droplet delivery⁷ device including a tube-shaped piezoelectric transducer for the airflow channel (13) in one embodiment of the invention.

[0075] FIG. 16A illustrates a cross-sectional side plan view of a droplet delivery device including an impingement structure being hemisphere, cup, dome, and the like (16) structure that may include high intensity’ focused ultrasound (HIFU) to reduce droplet size from droplets produced by an ejector plate (2) in one embodiment of the invention.

[0076] FIG. 16B is an illustration of a droplet delivery device in an alternative embodiment of FIG. 16A wherein the impingement structure includes a hole (17) at the apex in one embodiment of the invention.

[0077] FIG. 17 is a cross-sectional side plan view of a droplet delivery device with ultrasound generators or speakers (15) providing droplet size reduction in an embodiment of the invention. [0078] FIG. 18 is a photographic image showing droplets impinged on an impingement plate prior to plate vibration (larger droplet show) in an embodiment of the present invention. [0079] FIG. 19 is a photographic image showing aerosolization of droplets from the impingement plate prior during vibration (aerosol (200) shown in circled area) in an embodiment of the present invention.

[0080] FIG. 20 is a schematic diagram of a droplet delivery device including a passive vibrating plate (9) that does not vibrate on its own but is connected, via a rod or similar attachment and support structure (8), to the vibrating ejection member (4) (such as a transducer or piezo element) that is driving the ejector plate (2) in one embodiment of the invention.

[0081] FIG. 21 is a schematic diagram of a droplet delivery device including a passive vibrating plate (9) that does not vibrate on its own and is connected to a secondary vibrating member (1 1) via a rod or similar attachment (8) and support structure (such as a transducer or piezo element), while the secondary vibrating member does not drive the ejector in one embodiment of the invention.

[0082] FIG. 22 - 24 are examples of using an embodiment of the multi-stage droplet reduction device. The figures show droplet size data for an embodiment. Each figure show s data tested ten times. FIG. 22 and Table 2 are data collected from adding a vibrating plate operating at 2.4 MHz. FIG 23 and Table 3 shows data collected from adding a heated plate operating at 80 °C. FIG. 24 and Table 4 shows data collected from adding a heated plate operating at 60 °C.

[0083] FIG. 25 - 28 are graphs modeling the life-time of droplets at different temperatures. The x-axis of the graphs is the base diameter of a hemisphere droplet sitting on the surface of a heated plate. Four temperatures of heated plates were modeled: 40 °C. 60 °C, 60 °C, and 80 °C. The calculations assume 50% humidity and a 90-degree contact angle on the droplet. FIG 25 is a graph of droplet lifetime vs base diameter for plates heated to 40 °C and 60 °C for droplets sizes 1 to 20 pm. FIG 26 is a graph of droplet lifetime vs base diameter for plates heated to 40 °C and 60 °C for droplets sizes 1 to 100 pm. FIG 27 is a graph of droplet lifetime vs base diameter for plates heated to 80 °C and 100 °C for droplets sizes 1 to 20 pm. FIG 28 is a graph of droplet lifetime vs base diameter for plates heated to 80 °C and 100 °C for droplets sizes 1 to 100 pm.

DETAILED DESCRIPTION

[0084] With reference to FIGS. 1-21, the following table sets forth reference numerals for depicted elements:

[0085] Embodiments of the invention include a droplet delivery device that includes an ejector plate (2) that produces an aerosol (200) with larger droplets in a first ejection stage. Ejection with an ejector plate may utilize ring mode ejection and components, push mode ejection and components, and other known aerosol and nebulizer ejection mechanisms known in the art. Within an airflow channel (13), that leads to an inhalation outlet, such as a mouthpiece exit (1) or nosepiece outlet, of the droplet delivery device, an impingement surface is positioned perpendicular to or at an angle to (i.e. not parallel to (not 0° or 180°) the aerosol flow path from the ejector plate shown in FIG. 4). In some embodiments, the aerosol flow path from the ejector path at the first ejection stage may be in the same direction as the airflow path. In other embodiments, the aerosol flow path from the ejector plate at the first ejection stage may be in a different direction from the airflow path.

[0086] In embodiments of the invention, the impingement surface preferably vibrates, such as either by a power actuator or transducer known from push mode (FIG. 1) and ring mode ejection technologies, including such actuator or transducer being coupled to the impingement surface. In embodiments the actuator or transducer that vibrates an impingement surface is in addition to an ejector plate actuator, including each separate actuator providing different frequencies of oscillation to the respective ejection plate and impingement surface. In other embodiments a single shared actuator could be coupled to both an impingement surface and to an ejector plate (2) to cause vibration of both (FIG. 13 and FIG. 20).

[0087] In further embodiments, the impingement surface, such as a vibrating impingement plate (5), comprises piezoelectric material that vibrates when powered, preferably by one or more batteries of the droplet delivery device, FIG. 2.

[0088] In another embodiment, the impingement surface is roughly the same diameter as the ejected stream of droplets, FIG. 2.

[0089] In a different embodiment, the impingement surface is larger than the ejected stream of droplets as seen in FIG. 3.

[0090] In some embodiments, the impingement surface may comprise one or more of the following:

• Piezoelectric disc

• Vibrating member with a hom surface face of an actuator/transducer

• A piezoelectric cone (14) with both ends of the cone open (FIG. 14)

• Piezoelectric tube (6) (FIG. 15)

• Piezoelectric disc with wicking material connected

• A piezoelectric hemisphere, cup. dome, or HIFU (16) (FIG. 16A)

• A piezoelectric hemisphere, cup, dome, or HIFU (16) with ahole (17) at the apex (FIG. 16B).

• Laminated piezoelectric disc

• A metal plate/thin film metal/thin film plastic bonded to the piezoelectric disc

• Coated piezoelectric disc (hydrophilic, hydrophobic)

• Surface acoustic wave (SAW) device

• A plate or film that is vibrated by a piezoelectric transducer, (including separate piezo or the same piezo that creates the aerosol)

• Ring mode as the vibrating plate (further description below)

• Vibrating plate (any of above) with aperture/holes (further description below)

• Multiple plates where any vibrating plate can be any of the above. There can be static plates (7) with holes in them (2um to 10mm in diameter) before any of the vibrating plates. This will increase the velocity of the droplets giving them more momentum causing smaller droplets to smash into the vibrating plate. The plate with holes also increases inhalation resistance. • Multiple plates where the first vibrating plate is a plate, and the second one is a piezoelectric tube (6) as seen in FIG. 6.

[0091] In some embodiments, an impingement surface may not include apertures. In further embodiments an impingement surface may not vibrate and be “static’’ with or without apertures (7).

[0092] Impingement members or plates may include hydrophobic or hydrophilic coatings depending on the liquid composition to be aerosolized and the intended use of such composition. Liquid compositions used with the multi-stage droplet size reduction embodiments of the invention may include any therapeutic and non-therapeutic substances preferably for inhalation by a user, including nicotine compositions, cannabis-derived substances, medicaments and pharmaceuticals, genetics substances, microorganisms, vaccines, biologies, and other compositions described in patent and patent application disclosures incorporated herein by reference. In other embodiments, compositions may be of any t pe having utility in a variety of applications and may be delivered with pressurized gas (including air) in combination with reduced-size droplets produced by techniques and components described herein - such as substances that are not necessarily inhaled but might be administered to objects or other matter, including foodstuffs, paints, scented aerosol, fogging effects, pesticides, conducting aerosol chemical reactions, and other applications benefitting from small droplets in aerosol production.

[0093] In some embodiments, a pump may be provided in a droplet delivery device that sprays on to a vibrating ejection member (4) that is not push mode or ring mode to create an initial aerosol stream (200) with larger droplets that will impinge on one or more subsequent impingement surfaces to reduce the droplet size.

[0094] Droplet delivery devices of the invention may be provided with different distances between an ejector plate (2) and an impingement surface whereby smaller droplets are generated when an impingement surface is closer to an ejector plate and larger droplets result when the impingement and ej ector plates are further apart. In some embodiments, a user may adjust the distance of an impingement surface with respect to an ejector plate to control and change the droplet size that exits, including as inhaled, the outlet for the airflow channel (13) and droplet delivery device. Where a distance-adjustable impingement surface is provided relative to an ejector plate, a user might move the two closer to achieve smaller droplets (such as reducing irritation of the emitted droplets if they have a larger size) or might increase the distance between the ejector plate and impingement surface to obtain a certain feeling from larger droplets. It may also be desirable to have smaller or larger droplet sizes to control how deep an aerosol may flow into the pulmonary system, to control concentration of substances delivered to a user, and for other commercial or industrial reasons that depend on the desired results of application of the aerosol droplets from the droplet delivery device.

[0095] In some embodiments, a user may inhale differently or change the size of the airflow channel (13) outlet to increase or decrease the inhalation strength so as to create different droplet sizes and sensations.

[0096] Additionally, vibrating pieces or speakers (15) can be used to generate ultrasound frequencies. These frequencies can be aimed at the aerosol stream (200) with a goal of breaking droplets apart into smaller droplets. An example of this can be seen in FIG. 17.

[0097] Because a vibrating impingement surface may produce heat that could cause malfunction of the device or deleterious effect on compositions that are aerosolized, in some embodiments, coatings that resist heat or help cool the impingement surface may be applied. Additionally, or alternatively a temperature sensor or current monitor can be coupled to the impingement surface to limit current/stop current/or otherwise alter operation of the device to cool down the impingement surface before it gets too hot or draws too much cunent.

[0098] In some embodiments the vibrating impingement surface could also be kept below a temperature that would result in undesirable degradation (such as resulting in toxic or unhealthy chemical components or residue) of compositions being aerosolized for administered treatments. It will be appreciated that the temperature to be monitored and controlled for avoiding such degradation will depend on the type of composition. In some embodiments the temperature of the vibrating impingement surface will be maintained below around 80 degrees Celsius, or below around 70 degrees Celsius, or below around 60 degrees Celsius, or below around 50 degrees Celsius. It will be appreciated that the temperature can be controlled via a temperature sensor and controlling the power and thereby the vibration speed (including off/on vibration operation) of the impingement surface to stay below the target temperature that would result in degradation.

[0099] In some embodiments of the invention, an initial ejection stage of aerosol has an average droplet size of about 60 Microns (larger droplets) and impingement of the initial aerosol with larger droplets reduces the droplet size to an average of 4 Microns (smaller droplets). Accordingly, embodiments of the invention result in a smaller percentage of midsize and larger droplets using multi-stage droplet size reduction whereby impingement provides one or more additional stages beyond the initial aerosol stage to subsequently generate increasingly smaller droplets in the aerosol stream (200) to exit the airflow channel (13) of the droplet delivery device. [00100] One of the benefits of the multi-stage droplet size reduction is that where an ejector plate (2) has larger holes in a first ejection stage, as compared to the smaller hole size of ring mode and push mode ejection plates that require more power to create smaller droplet sizes through those smaller holes in single stage ejection from ejector to the droplet delivery device outlet, droplet devices of the invention can use much less power on the front end (because not as much power is needed for droplets to generate from larger holes) and then less comparative power is needed to power one or more impingement members in the droplet size reducing stages. It will be appreciated that by using less power to create desirable smaller droplets, there is benefit to the environment, devices are less expensive to manufacture where smaller batteries are needed, devices may carry longer battery life and number of uses before a battery needs to be recharged or replaced, and other costs and environmental benefits. In further embodiments, the ability to provide larger holes in an ejector plate of a multi-stage droplet size reduction-type delivery device may also reduce the amount of shear that otherwise is expected to affect the droplets, including encapsulated droplets like liposomes.

[00101] In some embodiments, a vibrating impingement member (10) or plate (5) could be attached to the ejector plate (2) or plate so that both members vibrate while using the same battery power that might otherwise have driven only an ejector plate in single stage aerosol generation, as seen in FIG. 13 and FIG. 20.

[00102] In some embodiments the diameter, or other sizing of an impingement surface in an airflow channel (13), may be changed for different droplet delivery devices to create different airflow (100) around the impingement surface (including where an impingement surface has no apertures) or through the impingement surface if it has aperture. The airflow direction and velocity may be changed by changing the sizing of the impingement surface positioned in the airflow channel. In some embodiments, an adjusting camera shutter-type member that includes an aperture that can be opened and closed may be provided between an ejector plate (2) and impingement surface. Such shutter-type member could be closed to allow the initial aerosol from ejector to build up and then it could be opened after a preferably amount of time to related the aerosol stream (200) through the aperture to hit the impingement surface and allow airflow (100) for smaller droplets to be produced and pulled out of the device from the airflow channel. In some embodiments the shutter-type member could be partially opened and closed (i.e. changing the diameter to shutter aperture) to change the droplet size of the aerosol stream from the droplet delivery device.

[00103] In embodiments of the invention, inertial filtering from the multi-stage reduction of droplet size also helps avoid liquid build up in the device and on the ejector and is self-cleaning since the accumulation of liquid on a vibrating impingement surface is discouraged where the vibration immediately breaks down any such liquid and larger droplet sizes into smaller droplet sizes that can be carried out of the device with the airflow (100) or can contact the ejector plate (2) to be aerosolized again and be broken down by the impingement surface.

[00104] In one embodiment of the invention, multiple impingement surfaces can each have smaller and smaller apertures, i.e. a multi step down of impingement meshes, so that droplet sizes must be increasingly smaller to pass through each subsequent mesh aperture size and finally exit the droplet device only at a preferred very small droplet size dictated by the last impingement mesh. An example of this is seen in FIG. 5.

[00105] In another embodiment of the invention, a ring mode vibrating plate may be provided as a vibrating impingement surface. In one embodiment, an ejector plate (2) with hole sizes anywhere from 2-30 um, and preferably having 5-10-um holes, is held taut by a piezoelectric anulus and acts as the impingement surface.

[00106] In another embodiment of the invention, multiple vibrating members/homs could be provided in the handheld portion of a droplet delivery device to separately couple to the ejector plate (2) and to one or more impingement members, as seen in FIG 21. More specifically, a first vibrating ejection member (4) could be coupled to vibrate the ejector plate and a second vibrating member (11) could be coupled, such as by a rod (8) or similar coupling element capable of being vibrated by the second vibrating member, to an impingement surface as an alternative to providing a vibrating member that uses piezoelectric material or a powered piezoelectric plate. The second vibrating member will be appreciated as transferring the vibration along the rod or similar coupling mechanism to vibrate the impingement surface (or plate). In some instances, the rod or coupling mechanism between the second transducer and the impingement member could include a membrane (3), coating or be compromised of nontoxic materials. In further embodiments, multiple additional vibrating members/homs with respective coupling mechanisms could be provided if multiple other impingement surfaces are provided downstream in the droplet delivery device. In still further embodiments, an additional vibrating member/hom could be coupled to vibrate a plurality of impingement members or plates.

[00107] In various embodiments, droplet delivery devices of the invention may include different types of batteries. For example, lithium iron phosphate could be used as a safer alternative than a lithium ion. In some embodiment, the lower voltage and lower driving time for multi-stage droplet size reduction will allow use of a battery that is smaller than a cunent batery size of 45.5mm x 16.5 mm x 3.5 mm that is used in embodiments of ring and push mode with single stage droplet generation.

[00108] In embodiments, airflow (100) through an airflow channel (13) entering through an airflow inlet (12) of a droplet deliver}' device using multi-stage droplet size reduction could be:

• In parallel with the ejection aerosol path (200), with inlet airflow (100) around the ejector (FIG. 1 - FIG .6)

• Perpendicular to the ejection aerosol path (200), like a tube (6) with two open ends (FIG. 8, FIG. 9, and FIG. 12 A)

• Perpendicular to the ejection aerosol path (200). where only the mouthpiece is open

• At an angle to the ejection aerosol path (200) with the ejection aerosol stream being perpendicular or angled to an impingement surface, such as vibrating impingement plate (5) (FIG. 7 and FIG. 10).

[00109] These embodiments can include any impingement surface, not limited to, but as an example include a vibrating impingement member (10) as an impingement surface with the airflow (100) at an angle to the ejection as seen in FIG. 7. A vibrating impingement member as an impingement surface with the airflow perpendicular to the aerosol stream (200) as seen in FIG. 8. A vibrating impingement plate (5), or a heated plate, perpendicular to the aerosol stream as seen in FIG. 9. A vibrating impingement plate (5), or heated plate, at an angle to the airflow' that is also at an angle to the aerosol stream as seen in FIG. 10.

[00110] Additionally, the airflow' can come in at multiple points, or airflow' inlets (12), and exit to the mouthpiece (1). This can be seen in FIG. 11 with a vibrating impingement member (10) as the impingement plate or FIG. 12B with a vibrating impingement plate (5) or heated plate.

[00111] In some embodiments of the invention, a collection plate could be provided in combination with an impingement surface and/or an ejector plate to wick accumulations of liquid back into a liquid reservoir that supplies the liquid for aerosolization. In further embodiments, a ring mode-based impingement plate could be combined with this wicking function so that the ring mode impingement plate vibrates and can both wick liquid through the holes back into a reservoir or similar liquid supply holding mechanism while also vibrating some accumulated liquid off of the impingement plate.

[00112] In embodiments, composition formulations preferable for use in multi-stage droplet size reduction include compositions with liquid having lower cohesive forces and with lower surface tension such as ethanol. Lower surface tension liquids preferable for use in embodiments of the invention can be pharmaceuticals or nicotine/cannabanoids. including as described in disclosures incorporated herein by reference.

EXAMPLE 1

[00113] In certain testing of two-stage droplet size reduction, initial composition formulations were developed to cover a wide range of surface tensions with a 3-point testing experiment (high/medium/low).

[00114] Surface tensions range from the highest at ~72 mN/m with pure water (excluding mercury) down to ~16 mN/m with diethyl ether. Surface tension is a property⁷ of the surface of a liquid that allow s it to resist an external force, this property is dependent on the cohesive forces between the liquid molecules. The cohesive forces are based on weak molecular interaction between the liquid molecules, these forces include but not limited to: dipole-dipole attraction, hydrogen bonding, Van der Waals forces (London dispersion attraction), and can also include ionic bonding.

[00115] If a chemical is added to a solution that disrupts these interactions, then the surface tension will decrease. The severity⁷ of this disruption is proportional to the decrease in surface tension. Chemicals that greatly decrease surface tension include but not limited to: surfactants, detergents, polar head hydrocarbons (e.g. lipids, fatty⁷ acids), alcohols and aromatic rings (e.g. benzoic acid).

[00116] Formulations that were used and preliminary data (Table 1) are as follows:

[00117] Albuterol: 1.205% (w/w) albuterol sulfate, 0.05% (w/w⁷) EDTA disodium salt dihydrate, and pH adjusted to 4.0 with hydrochloric acid.

[00118] Nicotine: 5% (w/w) free base nicotine, 0.94% (w/w) benzoic acid, 3.54% (w/w) lactic acid, 10% (w/w) glycerin

[00119] Cannabidiol (CBD): 5% (w/w) CBD, 5% (w/w) glycerin, 25% (w/w) propylene glycol, 35.75% (w/w) ethanol.

[00120] Preliminary⁷ data:

Table 1 [00121] As shown in Table 1, a useful way of representing the volume size distributions is with DxlO, Dx50 and Dx90 values. These are defined as threshold values, where 10%, 50% and 90% of drop sizes in the system are smaller or equal to them, respectively.

[00122] EXAMPLE 2

[00123] In FIGS. 22 - 24, data is presented for three iterations of the “Viking”, i.e., droplet size reduction alternative designs. FIG. 22 and Table 3 shows a data set collected from a vibrating impingement plate (5) being operated at 2.4 MHz. FIG 23 and Table 4 shows a data set collected from a heated plate (no vibration) with a constant temperature of 80 °C. FIG 24 and Table 5 show s a data set collected from a heated impingement plate (no vibration) with a constant temperature of 60 °C. The three data sets were all collected with the same ejector, positioned at a distance of 8 mm from the vibrated or heated plate. A single airflow inlet (12) was used for the testing setup. Each data set presented in the figures was collected by shooting the device 10 times into the Malvern with a flow⁷ rate of 2 SLM. The DxlO, Dx50, Dx90, and average DML values shown in Table 2 are each an average from the 10 shots. The residue percentage was collected once after the 10 shots were completed.

[00124] Table 2

[00125] Table 3: The below table contains the Dx(10), Dx(50), and the Dx(90) for ten shots of a device with a vibrating impingement plate (5) being operated at 2.4 MHz. The data below corresponds to the graph in FIG. 22.

[00126] Table 4: The below table contains the Dx(10), Dx(50), and the Dx(90) for ten shots of a device with a heated plate with a constant temperature of 80 °C. The data below corresponds to the graph in FIG. 23.

[00127] Table 5: The below table contains the Dx(10), Dx(50), and the Dx(90) for ten shots of a device with a heated plate with a constant temperature of 60 °C. The data below corresponds to the graph in FIG. 24.

EXAMPLE 3

[00128] Modeling outlining the evaporation of droplets with a heated impingement plate is provided in Example 3. FIG 25 - 28 shows images outlining the amount of time it takes for certain droplet sizes to evaporate off of a heated impingement plate. The x-axis of the graphs is the base diameter of a hemisphere droplet sitting on the surface of a heated impingement plate. Four temperatures of heated impingement plates were modeled: 40 °C, 60 °C, 60 °C, and 80 °C. The calculations assume 50% humidity and a 90-degree contact angle on the droplet. FIG 25 is a graph of droplet lifetime vs base diameter for plates heated to 40 °C and 60 °C for droplets sizes 1 to 20 pm. FIG 26 is a graph of droplet lifetime vs base diameter for plates heated to 40 °C and 60 °C for droplets sizes 1 to 100 pm. FIG 27 is a graph of droplet lifetime vs base diameter for plates heated to 80 °C and 100 °C for droplets sizes 1 to 20 pm. FIG 28 is a graph of droplet lifetime vs base diameter for plates heated to 80 °C and 100 °C for droplets sizes 1 to 100 pm.

EXAMPLE 4

[00129] An example of using a vibrating impingement plate as a vibrating impingement surface. FIG. 18 shows droplets impinged on the vibrating impingement plate before vibration has occurred. FIG. 19 shows aerosolization of the impinged droplets during vibration of the vibrating impingement plate.

[00130] Various embodiments of the invention have been described. It will, however, be evident that various modifications and changes may be made thereto, and additional embodiments may be implemented, without departing from the broader scope of the invention as set forth by the disclosure. This specification is to be regarded in an illustrative rather than a restrictive sense.

Claims

What is Claimed:

1. An aerosol delivery’ device comprising: an ejector configured to receive liquid composition and produce ejected aerosol in an airflow direction to an outlet configured to interface a mouth or nose; and a vibrating impingement element positioned non-parallel to the airflow direction of the ejected aerosol and between the ejector and the outlet.

2. The aerosol delivery device of claim 1 , further comprising one or more additional vibrating impingement elements between the ejector and the outlet.

3. The aerosol delivery device of claim 1, wherein the liquid composition includes a therapeutic agent.

4. The aerosol delivery device of claim 1, wherein the liquid composition includes a non-therapeutic agent.

5. The aerosol delivery’ device of claim 1, wherein the ejector includes a plurality’ of apertures.

6. The aerosol delivery device of claim 1, wherein the vibrating impingement element includes a piezoelectric material.

7. The aerosol delivery’ device of claim 1, wherein the ejector is configured for “push mode” operation.

8. The aerosol delivery device of claim 1, wherein the ejector is configured for “ring mode” operation.

9. The aerosol delivery device of claim 1, wherein the vibrating impingement element includes a plurality of apertures.

10. The aerosol delivery device of claim 1, wherein the vibrating impingement element is free of an aperture.

11. An aerosol delivery' device comprising: an ejector configured to receive liquid composition and produce ejected aerosol in an airflow direction to an outlet configured to interface a mouth or nose; and a heated impingement element positioned non-parallel to the airflow direction of the ejected aerosol and between the ejector and the outlet.

12. The aerosol delivery device of claim 11 further comprising one or more additional heated impingement elements between the ejector and the outlet.

13. The aerosol delivery device of claim 11, wherein the liquid composition includes a therapeutic agent.

14. The aerosol delivery device of claim 1 1, wherein the liquid composition includes a non-therapeutic agent.

15. The aerosol delivery device of claim 11, wherein the ejector includes a plurality of apertures.

16. The aerosol delivery device of claim 11. wherein the heated impingement element includes a piezoelectric material.

17. The aerosol delivery device of claim 11, wherein the ejector is configured for “push mode” operation.

18. The aerosol delivery device of claim 11, wherein the ejector is configured for “ring mode” operation.

19. The aerosol delivery device of claim 11, wherein the heated impingement element includes a plurality of apertures.

20. The aerosol delivery device of claim 11, wherein the heated impingement element is free of an aperture.

21. An aerosol delivery device comprising: an ejector configured to receive liquid composition and produce ejected aerosol in an airflow direction to an outlet configured to interface a mouth or nose; and at least on heated impingement element and at least one vibrating impingement element are positioned non-parallel to the airflow direction of the ejected aerosol and between the ejector and the outlet.

22. The aerosol delivery device of claim 21, wherein the liquid composition includes a therapeutic agent.

23. The aerosol delivery device of claim 21, wherein the liquid composition includes a non-therapeutic agent.

24. The aerosol delivery device of claim 21, wherein the ejector includes a plurality of apertures.

25. The aerosol delivery device of claim 21, wherein at least one heated or vibrating impingement element includes a piezoelectric material.

26. The aerosol delivery device of claim 21, wherein the ejector is configured for “push mode” operation.

27. The aerosol delivery device of claim 21, wherein the ejector is configured for “ring mode” operation.

28. The aerosol delivery device of claim 21, wherein at least one heated or vibrating impingement element includes a plurality of apertures.

29. The aerosol delivery device of claim 21, wherein at least one heated or vibrating impingement element is free of an aperture.

30. An aerosol delivery device comprising: a vibrating ejector plate coupled to a supply of a liquid composition; and one or more vibrating or heated impingement elements dow nstream from the ejector plate positioned in an airflow channel between the vibrating ejector plate and an inhalation outlet of the airflow channel.

31. The aerosol delivery device of claim 30, wherein the liquid composition includes a therapeutic agent.

32. The aerosol delivery' device of claim 30, wherein the liquid composition includes a non-therapeutic agent.

33. The aerosol delivery device of claim 31. wherein the ejector plate includes a plurality of apertures.

34. The aerosol delivery device of claim 31, wherein at least one impingement element includes a piezoelectric material.

35. The aerosol delivery device of claim 31, wherein the ejector plate is configured for “push mode” operation.

36. The aerosol delivery device of claim 31, wherein the ejector plate is configured for “ring mode” operation.

37. The aerosol delivery device of claim 31, wherein at least one impingement element includes a plurality of apertures.

38. The aerosol delivery device of claim 31, wherein at least one impingement element if free of an aperture.