Enhanced formulations for aerosol delivery

Abstract

Solutions for administering inhaled droplets from a droplet delivery device. The droplet delivery device includes compositions formulated with lower surface tensions to generate an aerosol with droplet sizes that provide an improved sensory experience for users.

Description

ENHANCED FORMULATIONS FOR AEROSOL DELIVERYCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 63 / 735,806 filed December 18, 2024, 63 / 702,131 filed October 1, 2024, 63 / 557, 937 filed February 26, 2024, and 63 / 626,835 filed January 30, 2024, which are all incorporated herein by reference in their entireties.BACKGROUND OF THE INVENTION

[0002] Embodiments of this disclosure generally relate to compositions and methods for administering low surface tension compositions via droplet delivery devices.

[0003] This application incorporates herein by reference in their entireties: U.S. Provisional Application Nos. 63 / 735,806, 63 / 557,937 63 / 605,917, 63 / 702,131, 63 / 701,564, and 63 / 626,83, PCT Application No. PCT / US24 / 58487, and U.S. Patent No. 11,793,945.BRIEF DESCRIPTION OF THE DRAWINGS

[0004] FIG. l is a cross-sectional schematic view of a push mode droplet delivery device including an ejector plate that is coupled with, but not fixed to, an electronic transducer to generate aerosol .

[0005] FIG. 2 is cross-sectional schematic view of a droplet delivery device with a container assembly holding liquid to be ejected, push mode ejector mechanism, and a filter in the ejection channel so that the aerosol with droplets moves through the filter.DETAILED DESCRIPTION

[0006] The surface tension of a solution affects the aerosol characteristics generated when the solution is actuated through our device. Previously, our standard solution has been >96% water with a surface tension of 68 mN / m2. In embodiments, a lower surface tension allows aerosol particles to be broken into smaller sizes when ejected through our device. This is particularly important when a lower surface tension solution is combined with inertial filtering to remove large droplets and / or a secondary component which mechanically breaks down droplets (i.e., vibrating plate).

[0007] In one embodiment, a low surface tension solution is used with the device. The lower surface tension solution allows aerosol to be ejected with smaller particle sizes than our standard solution. The hole size and / or hole geometry of the ejector plate through which the solution is ejected can be adjusted to optimize the ejection for the surface tension of the solution. For example, using a smaller hole size ejector plate will result in smaller particles. The lower surface tension solution should yield smaller particle sizes than our standard solution when using the same hole size. This may allow the use of larger hole size ejector plates, increasing the amount of solution delivered without increasing the particle size of the aerosol.

[0008] In a preferred embodiment, a formulation with a surface tension of between 40 and 50 mN / m2is used.

[0009] In another embodiment, a formulation with a surface tension of between 28 and 40 mN / m2is used.

[0010] In another embodiment, a formulation with a surface tension of between 50 and 68 mN / m2is used.

[0011] In a preferred embodiment, a formulation at the higher end of surface tension range can inhibit the leaking of solution through the ejector plate depending on the hole size used.

[0012] In a preferred embodiment, the solution contains one or more chemicals that provide a cooling sensation to the user (i.e., “cooling agents”). The cooling agent could consist of one or more of the following, alone or in combination: menthol; WS-23 (N- 2,3-Trimethyl-2- isopropyl butanamide); WS-3 (N-Ethyl-p-methane-3-carboxamide); commint oil; peppermint oil; spearmint oil; propylene glycol; glycerol

[0013] In one embodiment, a low surface tension solution is used in combination with a filter (100) that is placed in the ejection channel (80). An example includes the container assembly (20) shown in FIG. 2, wherein the filter is placed in the mouthpiece (10). The filter captures or breaks up larger aerosol particles. The filter in combination with a low surface tension solution allows for an aerosol composed of very fine particles to be delivered to the user. It is believed that the lower surface tension of the liquid helps the droplets break up upon impact. This can be upon impact of an inertial filter, upon impact of a foam filter, or upon impact of another filter. See such further disclosures in reference to U.S. Provisional Application Nos. 63 / 557,937, 63 / 605,917 and 63 / 701,564 and U.S. Pat. Pub. No. 2022 / 0008669, all of which are incorporated herein by reference.

[0014] In one embodiment, a low amount of heat is applied to the aerosol. Theoretically, this helps to break down larger particles in the aerosol. The heat applied to the aerosol is low enough to avoid the creation of excessive thermal byproducts from the solution. U.S. Patent No. 11,793,945 entitled “DROPLET DELIVERY DEVICE WITH PUSH EJECTION,” is incorporated herein by reference in its entirety, and describes methods of applying heat to the aerosol. In further embodiments, solutions described herein may be provided with or without heating in devices and with push ejection technology as described in U.S. Patent No. 11,793,945.

[0015] In one embodiment, a low surface tension solution is used in combination with the application of a low amount of heat. The low surface tension solution creates smaller particles than our standard solution when ejected. The application of heat then further reduces the particle size of the aerosol delivered to the user.

[0016] In a preferred embodiment, the aerosol is heated to between 70 and 80°C.

[0017] In another embodiment, the aerosol is heated to between 60 and 70°C.

[0018] In another embodiment, the aerosol is heated to between 50 and 60°C,

[0019] In another embodiment, the aerosol is heated to between 40 and 50°C.

[0020] In certain embodiments, compositions disclosed herein may be used with a "push mode" droplet delivery device, an example of which is shown in FIG. 1, that preferably does not include a heating requirement that could result in undesirable byproducts and comprises: a container assembly (20) with a mouthpiece (10); a reservoir (30) disposed within or in fluid communication with the container assembly to supply a volume of fluid of the composition, an ejector bracket (40) in fluid communication with the reservoir, the ejector bracket including an ejector plate (50) with a membrane (60) operably coupled to an electronic transducer (70) (such as an ultrasonic transducer preferably including piezoelectric material) with the membrane between the transducer and the ejector plate, wherein the ejector plate includes a plurality of openings formed through the ejector plate's thickness, and wherein the transducer is coupled to a power source and is operable to oscillate the membrane and / or ejector plate and generate an ejected stream of droplets of composition through the ejector plate, and an ejection channel (80) within the container assembly conFIG.d to direct the ejected stream of droplets from the ejector plate to the outlet. This is referred to as "push mode" ejection and devices in embodiments of the push mode invention may be referred to as push mode devices. A non-limiting example of such a deviceis described in U.S. Patent No. 1 1,793,945 the disclosures of which are each incorporated herein by reference in their entirety.

[0021] Effective delivery of droplets deep into the lung airways require droplets that are less than about 5-6 microns in diameter, specifically droplets with mass mean aerodynamic diameters (MMAD) that are less than about 5 microns. However, for certain agents and uses, droplets about 1 pm or smaller for quick adsorption in the deep lung may be desirable, e.g., it may be desired to utilize droplets less than 4 pm, less than 3.2 pm, less than 3 pm, less than 2 pm, and less than 1 pm for the delivery nicotine to the deep lungs. The mass mean aerodynamic diameter is defined as the diameter at which 50% of the droplets by mass are larger and 50% are smaller. In certain aspects of the disclosure, in order to deposit in the alveolar airways, droplets in this size range must have momentum that is sufficiently high to permit ejection out of the droplet delivery device, but sufficiently low to overcome deposition onto the tongue (soft palate) or pharynx.

[0022] In certain embodiments, methods for generating an ejected stream of droplets from a fluid composition comprising nicotine for delivery to the respiratory system of user are provided. In certain embodiments, the ejected stream of droplets is generated in a controllable and defined droplet size range. By way of example, the droplet size range includes at least about 50%, at least about 60%, at least about 70%, at least about 85%, at least about 90%, between about 50% and about 90%, between about 60% and about 90%, between about 70% and about 90%, etc., of the ejected droplets are in the respirable range of below about 5 pm, below about 4 pm, below about 3.7 pm, below about 3.5 pm, below about 3.2 pm, below about 3.0 pm, below about 2 pm, between about 0.7 pm and about 4 pm, between about 0.7 pm and about 3.2 pm, between about 0.7 pm and about 3 pm, between about 0.7 pm and about 2.5 pm, between about 0.7 pm and about 2.0 pm, between about 0.7 pm and about 1.5 pm, between about 0.7 pm and about 1.0 pm, etc.

[0023] In certain aspects, the droplet delivery device is capable of delivering a defined volume of fluid (fixed dose) in the form of an ejected stream of droplets having a small average ejected diameter such that an adequate and repeatable high percentage of the droplets are delivered into the desired location within the airways, e.g., the alveolar airways of the user during use. In certain embodiments, the average droplet diameters may range from about 0.7 pm to about 5 pm, about 0.7 pm to about 4.7 pm, about 0.7 pm to about 4 pm, about 0.7 pm to about 3.2 pm, about 0.7 pm to about 2.5 pm, about 0.7 pm to about 1.3 pm, etc. In certain embodiments, the average droplet diameters may be less than about 4 microns, less than about 3 .2 microns, less than about3 microns, less than about 2 microns, less than about 1.5 microns, less than about 1 micron, etc. In certain embodiments, the average droplet diameters may range from about 1 pm to about 2 pm (e.g., about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0 pm). In certain embodiments, the average droplet diameters may range from about 3 pm to about 4 pm (e.g., about 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0 pm). In certain embodiments, the average droplet diameters may range from about 0.5 pm to about 1 pm (e.g., about 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 pm).

[0024] The average droplet diameters delivered by the droplet delivery device in fluid communication with a solution described in the present disclosure may be optimized based on clinical or sensory need or consumer preference. For example, average droplet sizes of less than or about 1 pm may limit irritation in the throat or mouth and so may be preferable.

[0025] In another embodiment, a push mode device has better stability to the flavor profiles than heated devices. The flavors do not change using the push mode device since there is no heating and the ejection does not chemically change the flavor ingredients. Whereas, in heated electronic nicotine devices, the atomizer (heating element) changes temperatures over time. This change in temperature causes the flavors to change over time due to variations in the heating. This is due to the thermal degradation of the flavor products that change as the temperature changes.

[0026] In another embodiment, the flavor profile of solutions delivered via a push mode device stays truer to the original flavor as the main ingredient is water. Propylene glycol and glycerol, which are the main ingredients in traditional vape solutions, affect the intended flavor due to these chemicals having their own unique flavor properties.

[0027] In one embodiment, a vibrating plate is placed in the aerosol path such that larger particles in the aerosol impact onto the plate. The plate uses vibration to break up the droplets that impact on it, creating a finer mist. See “MULTI-STAGE DROPLET REDUCTION DELIVERY DEVICE” application (U.S. Prov. App. No. 63 / 626,843 filed January 30, 2024 incorporated herein by reference) for details on the vibrating plate.

[0028] In one embodiment, a low surface tension solution is used in combination with a vibrating plate. The low surface tension solution creates smaller particles than our standard solution when ejected. The vibrating plate then further reduces the particle size of the aerosol delivered to the user.

[0029] In one embodiment, a solution with a viscosity at 25°C from 0.8000 to 3.000 mm2 / s is used. This solution can have an influence on the particles size of the droplets. As viscosity goesdown then the particle could also go down. This also is in combination of the surface tension of a solution.

[0030] In another embodiment, with a push mode ejection device, such as the device seen in FIG. 1, a solution with a viscosity at 25°C from 0.8000 to 3.000 mm2 / s is used. This solution can have an influence on the particles size of the droplets. As viscosity goes down then the particle could also go down. This also is in combination of the surface tension of a solution.

[0031] A test was done to compare the aerosol characteristics produced by a push mode device when using several different solutions. The aerosol particle size was measured with a Dekati Electrical Low Pressure Impactor (ELPI). The test was performed as follows:

[0032] Prime 2 x 3 = 6 shots, measure the mass ejection for reference.

[0033] First time ELPI 3; measure MMAD from ELPI. Record the mass ejection as well.

[0034] Table 1 includes the surface tensions of the solutions used in the test:

[0035] Table 1

[0036] Table 2 contains the particle sizes and mass ejections collected during each step of the test. The Dx(10), Dx(50), and Dx(90) values found in Table 2 are averages from three shots. Table 2 contains MMAD values from three individual shots on the ELPI, as well as the average of the three shots. The residue percentage found in Table 2 is the amount of solution deposited in the aerosol path; this is solution that was ejected but did not exit the mouthpiece.

[0037] Table 2. Particle size and mass ejection results from described device using various solutions:

[0038] In the above testing, a push mode device was used with a 1.8 pm hole size ejector. This device had a filter (100) in the mouthpiece (10), as seen in FIG. 2. The filter consisted of a piece of polyurethane open-cell foam dubbed “UFP80” (pore size = 80 ppi). This piece of foam was 3mm thick.

[0039] Physical properties and aerosol particle characteristics.

[0040] There are several different physical properties that influence our water-based formulations. Surface tension, viscosity, and density. In order to understand how a liquid droplet works we need to discuss the basic principles of the forces at work.

[0041] Surface tension is caused by strong intermolecular attractive forces which are referred to as cohesive forces. Cohesive force in liquid molecules are attracted to each other in all directions. However, at the surface of the liquid there are fewer molecules to be attracted to, this results in a stronger attraction (inward net force) to the molecules neighboring and below, which gives rise to surface tension. This surface layer creates a barrier from the outside atmosphere and the liquid. Water has the greatest surface tension of any liquid, other than liquid mercury. The high surface tension of water causes the surface to contract and to resist being stretched and / or broken.

[0042] Surface tension can be decreased in a couple of different ways. One way to decrease surface tension of a liquid is Increasing temperature. Adding chemicals that disrupt hydrogen bonding, Van der Waal forces, and other intermolecular forces will also decrease surface tension

[0043] In some embodiments, a droplet delivery device that does not heat the aerosols is used to deliver the formulations described in the present disclosure. The aerosol emissions in the device are ejected through means that do not increase the temperatures much over ambient temperature.

[0044] In some embodiments, compositions herein are composed of water at a concentration of about 80% (w / w) to about 95% (w / w). In some aspects, the compositions herein may comprise about 60% (w / w) to about 80% (w / w).

[0045] In some embodiments, compositions herein are composed of nicotine at a concentration of 0% (w / w) to 5% (w / w). In some aspects, the composition does not include any nicotine in the formulation.

[0046] In some embodiments, compositions herein may comprise of L-lactic acid at a concentration of 0% (w / w) to about 5% (w / w). In some aspects, the composition does not include any L-lactic acid.

[0047] In some embodiments, compositions herein may comprise of propylene glycol at a concentration of 0% (w / w) to about 15% (w / w). Propylene glycol is used as a solubilization agent as well as an excipient. These formulation composition aspects allow for the adjustments to the viscosity and surface tension of the water-based solutions in order to optimize the aerosol characteristics for the desired droplet diameter and mass ejection.

[0048] In some embodiments, compositions herein may comprise of ethanol at a concentration of 0% (w / w) to about 10% (w / w). Ethanol is used as a solubilization again as well as an excipient. These formulation composition aspects allow for the adjustments to the viscosity and surface tension of the water-based solutions in order to optimize the aerosol characteristics for the desired droplet diameter and mass ejection.

[0049] In some embodiments, compositions herein may comprise of L-menthol. The concentration of L-menthol can range from 0.1% (w / w) to about 1.0% (w / w). In order to create a soluble solution with L-menthol in water, ethanol and propylene glycol are needed. For a water and / or water-nicotine based solution, propylene glycol needs to be between 5% (w / w) to about 15% (w / w) and ethanol needs to be between 1% (w / w) and about 10% (w / w). For an L-menthol solution at a concentration of 0.8% (w / w) or lower, the minimum amount of ethanol is 2.5 % (w / w), and the minimum amount of propylene glycol is 10% (w / w). For L-menthol solutions at a concentration of above 0.8% (w / w), ethanol needs to be between 2.5% (w / w) to 10% (w / w) with 10% (w / w) propylene glycol.

[0050] In some embodiments, compositions herein may comprise of WS-23 (2- isopropyl- N, 2, 3 -trimethylbutyramide) in the concentration of 0.1% (w / w) to about 0.5% (w / w). In order to use WS-23 in a water based formulation ethanol concentration of 2.5% (w / w) to about 10% (w / w) are needed. In addition, propylene glycol at a concentration of 10% (w / w) is also needed.

[0051] In some embodiments, compositions herein may comprise of concentrated fruit extracts in the concentration of 0.1% (w / w) to about 5% (w / w).

[0052] In another embodiment, compositions herein comprised of concentrated fruit extract could require additional excipients in order to get the fruit extract into water- based solutions. Ethanol in the concentration of 1% (w / w) to 10% (w / w) might be needed.

[0053] In another embodiment, compositions herein comprised of concentrated fruit extract could require additional excipients in order to get the fruit extract into water- based solutions. Propylene glycol in the concentration of 1% (w / w) to about 15% (w / w) might be needed.

[0054] In another embodiment, compositions herein comprised of concentrated fruit extract could require additional excipients in order to get the fruit extract into water- based solutions. Ethanol in the concentration of 1% (w / w) to 10% (w / w), in addition to propylene glycol in the concentration of 1% (w / w) to about 15%, (w / w) might be needed.

[0055] In some embodiments, compositions herein may comprise of cyclodextrin at a concentration of 0.1% (w / w) to about 5% (w / w). Cyclodextrin is used as a solubilizing agent.

[0056] In another embodiment, cyclodextrin can be used by itself, or it can be use with ethanol at a concentration of 1% (w / w) to about 10% (w / w).

[0057] In another embodiment, cyclodextrin can be used with propylene glycol in a concentration of 1% (w / w) to about 15% (w / w).

[0058] In another embodiment, cyclodextrin can be used with both ethanol and propylene glycol.

[0059] In some embodiments, compositions herein comprise of flavoring chemicals in the concentration of 0.001% (w / w) to about 5% (w / w).

[0060] In another embodiment flavoring chemicals can be used by themselves, or can be used with ethanol at a concentration of 1% (w / w) to about 10% (w / w).

[0061] In another embodiment, flavoring chemicals can be used with propylene glycol in a concentration of 1% (w / w) to about 15% (w / w).

[0062] In another embodiment, flavoring chemicals can be used with cyclodextrin in a concentration of 1% (w / w) to about 5% (w / w).

[0063] In another embodiment, flavoring chemicals can be used with both ethanol and propylene glycol and / or cyclodextrin.

[0064] In some embodiments, a solution containing no nicotine is used in fluid communication with a droplet delivery device as part of a smoking cessation and / or nicotine cessation therapy. With this solution, the user is able to maintain the “hand to mouth” action associated with smoking or vape / e-cigarette use, without nicotine content. This may make it easier for some to reduce and eventually eliminate their inhaled nicotine use or cigarette smoking. The droplet delivery device may be connected to a mobile app that includes tracking and motivational features.

[0065] In certain embodiments, the methods and formulations of the disclosure may be used to treat various diseases, disorders and conditions, promote or regulate various physiologicalactivities, and combinations thereof, by delivering a fluid composition comprising nicotine to the respiratory system of a user. In this regard, the methods of the disclosure may be used to deliver nicotine locally to the respiratory system, and / or systemically to the body. In some embodiments, the methods and formulations of the disclosure may be used as part of a smoking cessation, nicotine cessation, and / or nicotine reduction therapy.

[0066] In some embodiments, the methods and formulations of the disclosure may be used in a product which requires a prescription from a doctor.

[0067] In some embodiments, the methods and formulations of the disclosure may be used in an over-the-counter product.

[0068] In some embodiments, the methods and formulations of the disclosure may be used in a consumer product.

[0069] The element numbers are provided in Table 3 for convenient reference with respect to the descriptions and FIG.s provided herein.Table 3. Element numbers

[0070] While described with reference to specific embodiments herein, the invention is intended to extend in scope to the full extent of the disclosure.COMPARATIVE EXAMPLE

[0071] Study Overview: A study was performed to compare the amounts of select compounds in the emissions of several inhaled nicotine products. The compounds of interest included nicotine, 3 alcohol sugars (di ethylene glycol, ethylene glycol, and propylene glycol), 14heavy metals (chromium, iron, nickel, copper, zinc, arsenic, cadmium, tin, silver, lead, beryllium, cobalt, selenium, and vanadium) and 10 organic compounds (acetaldehyde, acrolein, butyraldehyde, crotonaldehyde, diacetyl, formaldehyde, furfural, pentanedione, acrylonitrile, and benzene).

[0072] The products chosen for the study included a vape device (Vuse, R.J. Reynolds Vapor Company, Winston-Salem, NC, USA), a heat-not-burn device (IQOS, Philip Morris International, Stamford, CT, USA), and a non-heated push mode device (Bluesky, Pneuma Respiratory Inc., Boone, NC, USA). Bluesky and Vuse use a liquid solution containing nicotine to create aerosol. IQOS uses a tobacco stick, in which the tobacco is heated to a lower temperature than a regular cigarette to create a vapor. Vuse also heats the nicotine solution to create aerosol. The Bluesky device creates aerosol without the use of heat. Additionally, the Bluesky device is water based, with a solution that is 92% water. In contrast, the solution used in Vuse was 50:50 propylene glycol and glycerol respectively. Both Bluesky and Vuse used solutions with a 1.8% concentration of nicotine.

[0073] The devices used for this testing were all tobacco flavored. Three devices of the same style and flavor were tested for each product. The Vuse and IQOS devices were all purchased from vendors. The data recorded below is based on the average of the three devices for each product. The devices were ejected into fdter pads to collect the analytes. Once the analytes were collected, tests were run to determine the amount of nicotine, alcohol sugars, heavy metals, and organic compounds present. In the following data tables, the Bluesky device is labeled as “Pneuma Device”.

[0074] Methods: For aerosol analyses, vaping of the devices was carried out using SM450 20-port linear analytical smoking machines. Each e-cigarette device was placed into a holder and vaped according to the applicable analytical method(s) and collected on Cambridge filter pads, impingers, or other applicable media as required by the method. Each sample was vaped in replicates of three. Each replicate puff block consisted of fifty puffs. The vaping regime performed was one puff every thirty seconds with a three second duration and a volume of 55 mL collected using a "square" wave profile. Fully charged devices were used for testing.

[0075] For the combustible smoke analyses, smoking of the products was carried about using the SM450 20-port linear analytical smoking machines. Each product was placed into a holder and smoked according to the applicable analytical method(s) and collected on Cambridgefilter pads or impingers. Each product was smoked in replicates of three via the Canadian Intense (CINT) smoking regime, which is products smoked using a 55mL, two-second puff every 30 seconds using a bell curve. All of the ventilation holes were blocked using a piece of scotch tape. Five sticks per replicate was used for testing. Twelve puffs per stick was also used for testing for a total of sixty puffs per replicate. Fully charged devices were used for testing.

[0076] E-cigarette aerosol is collected on a 55-mm Cambridge filter pad (CFP) and an impinger containing 20 mL of ethanol. Once collection is complete, the filter pad is combined with the impinger contents and shaken for 20 minutes at 200 RPM. The final extract from each port is filtered and then combined with all other ports of the same brand to make one large composite. For the analysis, 1.0 mL of the composite is added to 10 mL of isopropyl alcohol (IP A), spiked with internal standard, and mixed. Extracts are analyzed by gas chromatography (GC) with flame ionization detection (FID) and thermal conductivity detection (TCD).

[0077] Nicotine and Alcohol Sugar Results: The following table shows the amount of nicotine and alcohol sugars collected from each sample, in milligrams per puff (mg / puff). The amount of nicotine fluctuates between different nicotine devices. Bluesky ejected 0.0686 mg / puff; Vuse ejected 0.0915 mg / puff; and IQOS was 0.0872 ug / puff Based on the amount of nicotine collected and the concentration of nicotine present in the solutions, we can compare the amount of total solution delivered per puff for the electronic nicotine delivery systems (ENDS) that contain a liquid solution (Vuse, Bluesky). Bluesky delivered 3.8 mg of total solution, and Vuse delivered 5.1 mg of total solution. From the nicotine data, Vuse delivered the most nicotine and total aerosol, followed by IQOS, and Bluesky.

[0078] Alcohol sugars, ethylene glycol and propylene glycol, were also measured. Propylene glycol is approved for food products. However, ethylene glycol is toxic at high concentrations and is mainly used in industrial products. The only device that showed ethylene glycol present in the collected aerosol was the Vuse device. However, the ethylene glycol level was below the limit of quantitation (LOQ), so an accurate amount could be determined. Propylene glycol was found in all tested devices, including the IQOS tobacco product. The amounts found in each device in decreasing order are: Vuse with 1.98 mg / puff, Bluesky with 0.182 mg / puff, and finally IQOS with 0.0215 mg / puff.

[0079] Metal Results: Heavy metals can be introduced in ENDS products either through the nicotine solutions / tobacco substrates, from the devices heating / ej ection mechanisms, and / or though the liquid pathway in the device. The following data table shows the amounts of heavy metals present in the tested devices in nanograms per puff (ng / puff). The metals that were tested for are: chromium, iron, nickel, copper, zinc, arsenic, cadmium, tin, silver, lead, beryllium, cobalt, selenium, and vanadium. The heavy metals that were not detected in any of the 4 products are: beryllium, cadmium, cobalt, lead, and silver. Selenium was detected in all devices but was under the LOQ and could not be quantified. Vanadium was present in all the liquid-based ENDS but was under the LOQ and could not be quantified. The Bluesky device showed no other detectable heavy metals. The Vuse device showed quantifiable heavy metals which were: copper at 2.36 ng / puff, nickel at 2.73 ng / puff, and zinc at 23.6 ng / puff. The Vuse also had detectable chromium, iron, and tin, but all these metals were under the LOQ so the actual amount could not be determined. IQOS tests detected arsenic in the sample; however, it was under the LOQ and could not be quantified. Overall, the only quantifiable heavy metals that were present were from the Vuse device.

[0080] Organic Compound Results: Organic compounds that were tested were chosen based on carcinogens or potential carcinogens. The following data table shows the amounts of specific organic chemicals present in the tested devices. The organic compounds that were investigated are as follows: acetaldehyde, acrolein, butyraldehyde, crotonaldehyde, diacetyl, formaldehyde, furfural, pentanedione, acrylonitrile, and benzene. The Bluesky and Vuse devices contained no traces of butyraldehyde, crotonaldehyde, furfural, acrylonitrile, or benzene. Bluesky showed trace amounts of acetaldehyde and formaldehyde. However, the amounts were under the LOQ and could not be quantified. Bluesky had no traces of acrolein. Vuse showed 244 ng / puff of acetaldehyde, 85 ng / puff of acrolein, 41 ng / puff of diacetyl, and 381 ng / puff of formaldehyde. Vuse also showed trace amounts of pentanedione, but the levels were under the LOQ. IQOS testing showed quantifiable amounts of all tested organic compounds. The amounts of each chemical found for IQOS are as follows: 8210 ng / puff acetaldehyde, 693 ng / puff of acrolein, 1470 ng / puff of butyraldehyde, 168 ng / puff of crotonaldehyde, 2600 ng / puff of diacetyl, 410 ng / puff of formaldehyde, 1710 ng / puff of furfural, 641 ng / puff of pentanedione, 10 ng / puff acrylonitrile, and 23 ng / puff of benzene.

[0081] 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. A droplet delivery device having an electronically actuated ejector in fluid communication with a container including a solution with a surface tension from2 2 about 28 nM / m to about 68 mN / m .

2. The droplet delivery device of claim 1 further comprising a fluid path between the actuated ejector and an electronic actuator.

3. The droplet delivery device of claim 1 further comprising a membrane between an electronic actuator and the electronically actuated ejector.

4. A method of optimizing the production of droplets for inhalation comprising: providing a first solution to an electronically actuated ejector of a droplet delivery device and generating droplets; and providing a second solution with a lower surface tension than the first solution to the electronically actuated ejector of the droplet delivery device after determining the first solution does not generate sufficiently small droplets from the droplet delivery device.

5. The method of claim 4, wherein the second solution has a surface tension from about2 228 nM / m to about 68 mN / m .

6. A droplet delivery device having an electronically actuated ejector in fluid communication with a container including a solution with a viscosity in a range of2 2 from about 0.8000 mm / s to about 3.000 mm / s at a temperature of 25°C.

7. A method of optimizing the production of droplets for inhalation comprising: providing a first solution to an electronically actuated ejector of a droplet delivery device and generating droplets; and providing a second solution with a lower viscosity than the first solution to the electronically actuated ejector of the droplet delivery device after determining the first solution does not generate sufficiently small droplets from the droplet delivery device.

8. The method of claim 7, wherein the second solution has a viscosity in a range of from2 2 about 0.8000 mm / s to about 3.000 mm / s at a temperature of 25°C.

9. A droplet delivery device having an electronically actuated ejector in fluid communication with a container including a formulation comprising a minimum of 80% water in combination with one or more of propylene glycol, glycerol, nicotine, lactic acid, and a flavoring component.

10. The droplet device of claim 9, wherein the electronically actuated ejector is configured to create droplets with diameters under 10 pm when ejected by the droplet delivery device.

11. The droplet delivery device of claim 10, further comprising a fluid path between the actuated ejector and an electronic actuator.

12. The droplet delivery device of claim 10, further comprising a membrane between an electronic actuator and the electronically actuated ejector.

13. The droplet delivery device of claim 9, further comprising a fluid path between the actuated ejector and an electronic actuator.

14. The droplet delivery device of claim 9, further comprising a membrane between an electronic actuator and the electronically actuated ejector.

15. A droplet delivery device comprising a mouthpiece and configured to electronically eject aerosol without incorporation of an electronic heating component that heats above ambient temperature.

16. A droplet delivery device of claim 15, further comprising a formulation comprised of 80% to 95% (w / w) of water.

17. A droplet delivery device of claim 15, further comprising a formulation comprised of 60% to 80% (w / w) of water.

18. The droplet delivery device of claim 16, wherein the formulation includes 0% to 5% (w / w) nicotine salt.

19. The droplet delivery device of claim 17, wherein the formulation includes 0% to 5% (w / w) nicotine salt.

20. The droplet delivery device of claim 18, wherein the formulation includes 0% to 5% (w / w) L- lactic acid to form the nicotine salt.

21. The droplet delivery device of claim 19, wherein the formulation includes 0% to 5% (w / w) L- lactic acid to form the nicotine salt22. The droplet delivery device of claim 20, wherein the formulation includes 0% to 15% propylene glycol23. The droplet delivery device of claim 21, wherein the formulation includes 0% to 15% propylene glycol24. The droplet delivery device of claim 20, wherein the formulation includes 0% to 10% ethanol25. The droplet delivery device of claim 21, wherein the formulation includes 0% to 10 % ethanol26. The droplet delivery device of claim 24, wherein the formulation includes 0.1% to 1.0% L- menthol27. The droplet delivery device of claim 25, wherein the formulation includes 0.1% to 1.0% L- menthol28. The droplet delivery device of claim 26, wherein the formulation includes 0.01% to 0.5% WS-23 (2-isopropyl-N,2,3-trimethylbutyramide)29. The droplet delivery device of claim 27, wherein the formulation includes 0.01% to 0.5% WS-23 (2-isopropyl-N,2,3-trimethylbutyramide)30. The droplet delivery device of claim 22, wherein the formulation includes 0.1% to 5% concentrated fruit extract31. The droplet delivery device of claim 23, wherein the formulation includes 0.1% to 5% concentrated fruit extract32. The droplet delivery device of claim 26, wherein the formulation includes 0.1% to 5% concentrated fruit extract33. The droplet delivery device of claim 27, wherein the formulation includes 0.1% to 5% concentrated fruit extract34. The droplet delivery device of claim 28, wherein the formulation includes 0.1% to 5% concentrated fruit extract35. The droplet delivery device of claim 29, wherein the formulation includes 0.1% to 5% concentrated fruit extract36. The droplet delivery device of claim 24, wherein the formulation includes 0.1% to 5% cyclodextrin37. The droplet delivery device of claim 25, wherein the formulation includes 0.1% to 5% cyclodextrin38. The droplet delivery device of claim 24, wherein the formulation includes 0.001% to 5% flavoring chemicals.

39. The droplet delivery device of claim 25, wherein the formulation includes 0.001% to 5% flavoring chemicals.