Electrically heated aerosol delivery system

Abstract

The present invention relates to an electrically heated aerosol delivery system for delivering aerosolized medicament particles to a user and comprising a cartridge and a device configured to receive the cartridge. The cartridge comprises a first compartment containing a source of a delivery enhancing compound, a second compartment containing a source of a medicament, a vaporizer for heating the medicament, and a transfer element for transferring the medicament from the second compartment to the vaporizer. The cartridge can further comprise an aerosol forming chamber in fluid communication with the first and second compartments. The device comprises an outer housing, a power source, temperature control means for controlling the temperature of the first compartment of the cartridge, and an electronic circuit configured to control the power from the power source to the temperature control means. The electronic circuit is configured to maintain the first compartment of the cartridge at a temperature between about 30°C and about 50°C. In use, the medicament reacts with the delivery enhancing compound in the gas phase to form aerosolized medicament-containing particles.

Description

[0001] This application is a divisional application of Chinese patent application No. PCT / EP2014 / 060225, Chinese application No. 201480025197.2, filed on May 19, 2014, entitled "Electrically Heated Aerosol Delivery System". Technical Field

[0002] This invention relates to a cartridge for an aerosol delivery system and a device configured to receive said cartridge. The invention also relates to an aerosol delivery system comprising a device and a cartridge for delivering aerosolized pharmaceutical agents such as nicotine salt particles to a user, and particularly to a smoking device for delivering aerosolized nicotine salt particles to a user. The invention further relates to a method for delivering aerosolized pharmaceutical agents such as nicotine salt particles to a user. Background Technology

[0003] So-called "electronic cigarettes," which evaporate liquid nicotine formulations to form an aerosol for inhalation by a user, and other electrically operated smoking systems are known in the art. For example, WO 2009 / 132793 A1 discloses an electrically heated smoking system comprising a housing and a replaceable mouthpiece, wherein the housing includes a power source and circuitry. The mouthpiece includes a liquid reservoir, a capillary wick having a first end extending into the liquid reservoir to contact the liquid therein, and a heating element for heating a second end of the capillary wick. In use, the liquid is transferred from the liquid reservoir to the heating element via capillary action in the wick. The liquid at the second end of the wick is evaporated by the heating element. The liquid preferably contains a tobacco-containing material comprising volatile tobacco flavor compounds that are released from the liquid upon heating.

[0004] Commercially available electronic cigarettes typically require significant power to generate an aerosol with the appropriate particle size for delivery to the user.

[0005] WO 2008 / 121610 A1 and WO 2011 / 034723 A1 disclose apparatus and methods for delivering nicotine or other pharmaceutical agents to a subject, wherein pyruvate reacts with nicotine or other pharmaceutical agents in the gas phase to form an aerosol of nicotine or pharmaceutical pyruvate particles. At room temperature, both pyruvate and nicotine are sufficiently volatile to form corresponding vapors, which react with each other to form nicotine pyruvate particles. However, at a given temperature, pyruvate has a higher vapor pressure than nicotine. As a result, the efficiency of the gas-phase reaction between pyruvate and nicotine is highly dependent on ambient temperature, which may adversely lead to inconsistent nicotine delivery to the user.

[0006] There is a need for an aerosol delivery system that operates with reduced power consumption compared to commercially available electronic cigarettes. There is also a need for an aerosol delivery system that allows for more consistent delivery of nicotine or other medications per puff compared to known devices used for delivering aerosolized nicotine salt particles. Summary of the Invention

[0007] According to the present invention, a cylinder is provided, comprising: a first compartment containing a source of a volatile delivery-enhancing compound; a second compartment containing a source of a pharmaceutical agent; an evaporator for heating the pharmaceutical agent; and a transfer element for transferring the pharmaceutical agent from the second compartment to the evaporator.

[0008] As further discussed below, the use of the cartridge according to the invention in an aerosol delivery system advantageously allows for more consistent drug delivery than in known devices for delivering aerosolized nicotine or pharmaceutical salt particles. That is, the drug delivery per aspiration during use of the cartridge according to the invention in an aerosol delivery system is more consistent than in known devices for delivering aerosolized nicotine or pharmaceutical salt particles. Furthermore, the drug delivery per aspiration during use of the cartridge according to the invention in an aerosol delivery system is more constant than in known devices for delivering aerosolized nicotine or pharmaceutical salt particles.

[0009] As used herein, the term "volatile" refers to a delivery-enhancing compound with a vapor pressure of at least about 20 Pa. Unless otherwise stated, all vapor pressures mentioned herein are vapor pressures at 25°C as measured according to ASTM E1194-07.

[0010] Preferably, the vapor pressure of the volatile delivery-enhancing compound at 25°C is at least about 50 Pa, more preferably at least about 75 Pa, and most preferably at least 100 Pa.

[0011] Preferably, the vapor pressure of the volatile delivery enhancement compound at 25°C is less than or equal to about 400 Pa, more preferably less than or equal to about 300 Pa, even more preferably less than or equal to about 275 Pa, and most preferably less than or equal to about 250 Pa.

[0012] In some embodiments, the vapor pressure of the volatile delivery enhancement compound at 25°C may be between about 20 Pa and about 400 Pa, more preferably between about 20 Pa and about 300 Pa, even more preferably between about 20 Pa and about 275 Pa, and most preferably between about 20 Pa and about 250 Pa.

[0013] In other embodiments, the vapor pressure of the volatile delivery-enhancing compound at 25°C may be between about 50 Pa and about 400 Pa, more preferably between about 50 Pa and about 300 Pa, even more preferably between about 50 Pa and about 275 Pa, and most preferably between about 50 Pa and about 250 Pa.

[0014] In other embodiments, the vapor pressure of the volatile delivery-enhancing compound at 25°C may be between about 75 Pa and about 400 Pa, more preferably between about 75 Pa and about 300 Pa, even more preferably between about 75 Pa and about 275 Pa, and most preferably between about 75 Pa and about 250 Pa.

[0015] In other embodiments, the vapor pressure of the volatile delivery enhancement compound at 25°C may be between about 100 Pa and about 400 Pa, more preferably between about 100 Pa and about 300 Pa, even more preferably between about 100 Pa and about 275 Pa, and most preferably between about 100 Pa and about 250 Pa.

[0016] A volatile delivery-enhancing compound may consist of a single compound. Alternatively, a volatile delivery-enhancing compound may consist of two or more different compounds.

[0017] When the volatile delivery-enhancing compound comprises two or more different compounds, the combination of the two or more different compounds has a vapor pressure of at least about 20 Pa at 25°C.

[0018] Preferably, the volatile delivery-enhancing compound is a volatile liquid.

[0019] Volatile delivery-enhancing compounds may comprise a mixture of two or more different liquid compounds.

[0020] Volatile delivery-enhancing compounds may comprise an aqueous solution of one or more compounds. Alternatively, volatile delivery-enhancing compounds may comprise a non-aqueous solution of one or more compounds.

[0021] Volatile delivery enhancers may contain two or more different volatile compounds. For example, a volatile delivery enhancer may contain a mixture of two or more different volatile liquid compounds.

[0022] Alternatively, the volatile delivery enhancer compound may comprise one or more non-volatile compounds and one or more volatile compounds. For example, the volatile delivery enhancer compound may comprise a solution of one or more non-volatile compounds in a volatile solvent, or a mixture of one or more non-volatile liquid compounds and one or more volatile liquid compounds.

[0023] In one embodiment, the volatile delivery-enhancing compound comprises an acid. The volatile delivery-enhancing compound may comprise an organic acid or an inorganic acid. Preferably, the volatile delivery-enhancing compound comprises an organic acid, more preferably a carboxylic acid, and most preferably an α-keto acid or a 2-oxoacid.

[0024] In a preferred embodiment, the volatile delivery-enhancing compound in the first compartment comprises an acid selected from 3-methyl-2-oxovalerate, pyruvate, 2-oxovalerate, 4-methyl-2-oxovalerate, 3-methyl-2-oxobutyric acid, 2-oxooctanoic acid, and combinations thereof. In a particularly preferred embodiment, the first compartment contains pyruvate.

[0025] In one embodiment, the volatile delivery-enhancing compound comprises ammonium chloride.

[0026] In a preferred embodiment, the volatile delivery-enhancing compound source comprises an adsorption element and a volatile delivery-enhancing compound adsorbed on the adsorption element.

[0027] As used herein, "adsorption" refers to the adsorption of a volatile delivery-enhancing compound onto the surface of an adsorption element, or into the adsorption element, or both. Preferably, the volatile delivery-enhancing compound is adsorbed onto the adsorption element.

[0028] The adsorption element can be formed from any suitable material or combination of materials. For example, the adsorption element may comprise one or more of glass, stainless steel, aluminum, polyethylene (PE), polypropylene, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), and BAREX®.

[0029] In a preferred embodiment, the adsorption element is a porous adsorption element.

[0030] For example, the adsorption element may be a porous adsorption element comprising one or more materials selected from porous plastic materials, porous polymer fibers and porous glass fibers.

[0031] The adsorption element is preferably chemically inert to enhance the delivery of volatile compounds.

[0032] The adsorption element can have any suitable size and shape.

[0033] In a preferred embodiment, the adsorption element is a generally cylindrical plug. In a particularly preferred embodiment, the adsorption element is a generally cylindrical porous plug.

[0034] In another preferred embodiment, the adsorption element is a generally cylindrical hollow tube. In another particularly preferred embodiment, the adsorption element is a generally cylindrical porous hollow tube.

[0035] The size, shape, and composition of the adsorption element can be selected to allow the desired amount of volatile delivery enhanced compound adsorption onto the adsorption element.

[0036] In a preferred embodiment, a volatile delivery-enhancing compound is adsorbed onto the adsorption element in a range of about 20 µl to about 200 µl, more preferably between about 40 µl and about 150 µl, and most preferably between about 50 µl and about 100 µl.

[0037] Adsorption elements advantageously serve as reservoirs for volatile delivery-enhancing compounds.

[0038] The adsorption element may be configured to deliver a volatile delivery-enhancing compound from the first compartment into the air being drawn into the intake passage. For example, the adsorption element may include a capillary material to deliver the volatile delivery-enhancing compound from the first compartment into the air being drawn into the intake passage via capillary action. In some embodiments, the adsorption element may include a capillary wick to deliver the volatile delivery-enhancing compound from the first compartment into the air being drawn into the intake passage via capillary action.

[0039] The use of volatile delivery-enhancing compounds advantageously allows aerosol delivery systems comprising the cartridge according to the invention to operate with reduced power consumption compared to commercially available e-cigarettes. The power consumption of the aerosol delivery system of the invention can be reduced by decreasing the power required to vaporize the drug, as the volatile delivery-enhancing compounds will increase the delivery rate of the drug to the user. In contrast, in commercially available e-cigarettes, additional power is required to vaporize the nicotine formulation to generate smaller aerosol particles in order to increase the delivery rate of nicotine to the user. By reducing the power required to generate an aerosol suitable for delivery to the user, the operating temperature of the aerosol delivery system comprising the cartridge according to the invention can also be advantageously reduced.

[0040] Thus, the present invention allows for the provision of a cost-effective, compact, and easy-to-use aerosol delivery system. Furthermore, compared to commercially available electronic cigarettes, the pharmacokinetic rate of the drug can be advantageously improved by using an acid or ammonium chloride as a delivery-enhancing compound in the cartridge according to the invention.

[0041] In a preferred embodiment, the cartridge further includes an aerosol forming chamber in fluid communication with the first and second compartments. In use, the pharmaceutical agent reacts with a volatile delivery-enhancing compound in the aerosol forming chamber in the gas phase to form atomized pharmaceutical-containing particles.

[0042] Preferably, the cylinder further includes at least one air inlet upstream of the first compartment and at least one air outlet downstream of the aerosol forming chamber, the at least one air inlet and the at least one air outlet being arranged to define an airflow path extending from the at least one air inlet via the first compartment, the evaporator and the aerosol forming chamber to the at least one air outlet.

[0043] As used herein, the terms “upstream” and “downstream” are used to describe the relative position of a component or part of a cylinder, aerosol delivery device, and aerosol delivery system according to the invention with respect to the direction in which air is drawn through the cylinder, aerosol delivery device, and aerosol delivery system during their use.

[0044] As used in this article, the term "air inlet" is used to describe the passage of air through one or more holes in its intake tube.

[0045] As used in this article, the term "air outlet" is used to describe one or more holes through which air can be drawn from the cylinder.

[0046] In a preferred embodiment, the at least one air inlet includes a plurality of perforations provided in the outer casing of the cylinder. Preferably, the perforations extend circumferentially around the outer casing.

[0047] Preferably, the melting point of the agent is below about 150 degrees Celsius.

[0048] Optionally or additionally, preferably, the boiling point of the agent is below about 300 degrees Celsius.

[0049] In some preferred embodiments, the agent comprises one or more aliphatic or aromatic, saturated or unsaturated nitrogen-containing bases (nitrogen-containing basic compounds), wherein the nitrogen atom is present in a heterocyclic or acyclic chain (substitution).

[0050] The pharmaceutical preparation may contain one or more compounds selected from the following: nicotine; 7-hydroxyphenoxyacetylcholine; arecoline; atropine; bupropion; norephedrine (D-norpseudonym); chlorpheniramine; debucaine; dimethionine; dimethyltryptamine; diphenhydramine; ephedrine hydrochloride; maltine; hyoscyamine; isoarecoline; levofenol; lobeline; pinene; phenoxyacetylcholine; muscatine; procaine; pseudoephedrine; pyramine; raloctylcholine; ritodrine; scopolamine; cytisine; and ticlopidine; tobacco smoke components such as 1,2,3,4-tetrahydroisoquinoline, pseudoephedrine, neonicotinoids, cotinine, mesmin, nicotine, nicotine, and nornicotinoids; and anti-asthmatic drugs such as orsinol, propranolol, and terbutaline. Antianginal drugs, such as nicorandil, oxenolol, and verapamil; antiarrhythmic drugs, such as lidocaine; nicotinic agonists, such as scutellarin, 5-(2R)-acetidylmethoxy)-2-chloropyridine (ABT-594), and (S)-3-methyl-5-(l-methyl-2-pyrrolidinyl)isoxazole (ABT-594). 418) and (±)-2-(3-pyridyl)-l-azabicyclo[2.2.2]octane (RJR-2429); nicotinic antagonists, such as methyllycacotinine and mecaramine; acetylcholinesterase inhibitors, such as galantamine, pyridostigmine, physostigmine and tacrine; and MAO-inhibitors, such as methoxy-N,N-dimethyltryptamine, 5-methoxy-α-methyltryptamine, α-methyltryptamine, isopropylchlorohydrazine, isopropylnicotinamide, isozolidine, linezolid, moclobemide, N,N-dimethyltryptamine, phenethylhydrazine, phenethylamine, toloxacin, transphenylcyclopropylamine and tryptamine.

[0051] The preferred source of the drug is nicotine.

[0052] The reagent source may include an adsorption element and a reagent adsorbed on the adsorption element.

[0053] The second compartment may contain an adsorption element thereon on which a reagent is adsorbed. More preferably, the second compartment contains a porous adsorption element thereon on which a reagent is adsorbed. The porous adsorption element may contain one or more porous materials selected from porous plastic materials, porous polymer fibers, and porous glass fibers. The one or more porous materials may or may not be capillary materials and are preferably inert to the reagent. Particularly preferred porous materials will depend on the physical properties of the reagent. The one or more porous materials may have any suitable porosity for use with different reagents having different physical properties.

[0054] Introducing an adsorption element with the drug adsorbed on it into the second compartment can advantageously reduce the risk of drug leakage from the cylinder.

[0055] Furthermore, by selecting adsorption elements with suitable properties, the introduction of adsorption elements can allow for improved control of drug release.

[0056] In a preferred embodiment, the first compartment of the cartridge contains a volatile delivery-enhancing compound source, while the second compartment contains a nicotine source. The nicotine source may contain one or more of nicotine, nicotine base, nicotine salt (such as nicotine-HCl, nicotine-bitartrate, or nicotine-distartrate), or nicotine derivatives.

[0057] Nicotine sources can include natural nicotine or synthetic nicotine.

[0058] Nicotine sources may include pure nicotine, a solution of nicotine in water or a non-aqueous solvent, or a liquid tobacco extract.

[0059] Nicotine sources may also include electrolyte-forming compounds. These compounds may be selected from alkali metal hydroxides, alkali metal oxides, alkali metal salts, alkaline earth metal oxides, alkaline earth metal hydroxides, and combinations thereof.

[0060] For example, nicotine sources may include electrolyte-forming compounds selected from potassium hydroxide, sodium hydroxide, lithium oxide, barium oxide, potassium chloride, sodium chloride, sodium carbonate, sodium citrate, ammonium sulfate, and combinations thereof.

[0061] In some embodiments, the nicotine source may comprise an aqueous solution of nicotine, nicotine base, nicotine salt, or nicotine derivative and an electrolyte forming compound.

[0062] Optionally or additionally, the nicotine source may also contain other components, including but not limited to natural flavorings, artificial flavorings, and antioxidants. Preferably, the second compartment contains a liquid pharmaceutical source. Preferably, the second compartment is configured to hold between about 50 microliters and about 150 microliters of liquid pharmaceutical, more preferably about 100 microliters of liquid pharmaceutical.

[0063] The liquid agent has a boiling point suitable for use in an aerosol delivery system as described herein: if the boiling point is too high, the evaporator will not be able to evaporate the liquid agent. The liquid agent also has physical properties that allow the agent to be transferred from the second compartment to the evaporator by the transfer element. Preferably, the liquid agent has physical properties, including viscosity, that allow the liquid agent to be transferred from the second compartment to the evaporator via capillary action through the transfer element.

[0064] The evaporator is preferably located downstream of the first compartment so that the air drawn in through the cylinder passes through the first compartment before passing through the evaporator.

[0065] The evaporator preferably includes an electrically operated heater that can be connected to a power source. The heater preferably includes at least one heating element configured to heat the agent to form a vapor containing the agent. The heater may include a single heating element. Alternatively, the heater may include more than one heating element, such as two, three, four, five, six, or more heating elements. The one or more heating elements may be suitably arranged to most efficiently evaporate the agent. The cylinder preferably includes electrical contacts configured to couple to a power source in the aerosol delivery device to provide power to the at least one heating element.

[0066] The at least one heating element preferably comprises a resistive material. Suitable resistive materials include, but are not limited to: semiconductors such as doped ceramics, electrically "conductive" ceramics (e.g., molybdenum disilicide), carbon, graphite, metals, metal alloys, and composite materials made of ceramic and metallic materials. Such composite materials may comprise doped or undoped ceramics. Examples of suitable doped ceramics include doped silicon carbide. Examples of suitable metals include titanium, zirconium, tantalum, and metals from the platinum group. Examples of suitable metal alloys include stainless steel, alloys containing nickel, cobalt, chromium, aluminum, titanium, zirconium, hafnium, niobium, molybdenum, tantalum, tungsten, tin, gallium, manganese, and iron, and superalloys based on nickel, iron, cobalt, stainless steel, titanium, and iron-manganese-aluminum based alloys. In composite materials, the resistive material may optionally be embedded in, encapsulated by, or covered by an insulating material, or vice versa, depending on the energy transfer kinetics and desired external physicochemical properties. Examples of suitable composite heating elements are disclosed in US 5,498,855, WO 03 / 095688 A2 and US 5,514,630.

[0067] The at least one heating element may be in any suitable form. For example, the at least one heating element may be in the form of a heating blade, as described in US 5,388,594, US 5,591,368, and US 5,505,214. Alternatively, the at least one heating element may be in the form of a housing or substrate with different conductive portions, as described in EP 1 128 741 A1, or in the form of a resistive metal tube, as described in WO 2007 / 066374 A1. Alternatively, the at least one heating element may be a disc (end) heater or a combination of a disc heater and a heating needle or rod. Alternatively, the at least one heating element may be in the form of a metal etched foil insulated between two layers of inert material. In such embodiments, the inert material may comprise Kapton®, all-polyimide, or mica foil. Alternatively, the at least one heating element may be in the form of a sheet of material that can be wound around an evaporator. The sheet may be made of any suitable material, such as an iron-aluminum based alloy, an iron-manganese-aluminum based alloy, or a titanium alloy. The sheet can be rectangular or patterned, and when wound around the evaporator, the patterned shape can form a coil-like structure. Other alternatives include heating wires or filaments, such as Ni-Cr, platinum, tungsten, or alloy wires, as described in EP 1736 065 A1, or heating plates.

[0068] In a preferred embodiment, the at least one heating element comprises a coil of wire wrapped around the evaporator. In this embodiment, the wire is preferably a metal wire. Even more preferably, the wire is a metal alloy wire. The heating element may completely or partially surround the evaporator.

[0069] In an alternative embodiment, the evaporator may include an atomizer comprising the at least one heating element. In addition to the heating element, the atomizer may also include one or more electromechanical components, such as piezoelectric elements. Alternatively or additionally, the atomizer may also include elements utilizing electrostatic, electromagnetic, or pneumatic effects.

[0070] The transfer element may contain a porous material. The transfer element may have a first portion extending into the second compartment and a second portion adjacent to the evaporator.

[0071] Preferably, the transfer element comprises capillary material to transfer the reagent from the second compartment to the evaporator via capillary action. The capillary material may be a capillary wick having a first portion extending into the second compartment and a second portion adjacent to the evaporator. In use, the reagent is transferred from the second compartment to the evaporator via capillary action in the capillary wick. When the evaporator is started, the reagent in the second portion of the capillary wick evaporates to form a reagent-containing vapor.

[0072] Preferably, the evaporator is configured to heat the pharmaceutical agent in the second portion of the capillary to a temperature between about 60°C and about 150°C. More preferably, the evaporator is configured to heat the pharmaceutical agent in the second portion of the capillary to a temperature between about 65°C and about 120°C. Even more preferably, the evaporator is configured to heat the pharmaceutical agent in the second portion of the capillary to a temperature between about 70°C and about 100°C to form a pharmaceutically containing vapor.

[0073] The capillary wick can be a linear capillary wick having a first free end extending into the second compartment and a second free end adjacent to the evaporator. Alternatively, the capillary wick can be a coiled capillary wick. In such embodiments, the first portion of the capillary wick extending into the evaporator and the second portion of the capillary wick adjacent to the evaporator can be either the free end of the capillary wick or a coiled portion of the capillary wick. For example, the capillary wick can be a U-shaped capillary wick, wherein the curved portion of the U-shaped capillary wick extends into the second compartment and the free end of the U-shaped capillary wick is adjacent to the evaporator. Alternatively, the capillary wick can be a U-shaped capillary wick, wherein the free end of the U-shaped capillary wick extends into the second compartment and the curved portion of the U-shaped capillary wick is adjacent to the evaporator. It should be understood that any other suitable capillary wick shape may also be used.

[0074] The capillary wick can have a fibrous or sponge-like structure. For example, the capillary wick can contain multiple fibers or threads, which are typically arranged longitudinally along the cylinder, or the capillary wick can contain a sponge-like material formed into a rod shape along the longitudinal direction of the cylinder. The wick's structure forms multiple small pores or tubes through which the agent can be transported from the second compartment to the evaporator via capillary action. The capillary wick can contain any suitable material or combination of materials. Examples of suitable materials include ceramic-based or graphite-based materials in fibrous or sintered powder form. The capillary wick can have any suitable capillary action and porosity for use with agents having different physical properties such as density, viscosity, surface tension, and vapor pressure.

[0075] A porous material can be disposed between the capillary wick and the evaporator. The porous material can be any suitable material that allows the reagent to permeate and migrate from the capillary wick to the evaporator. The porous material is preferably inert to the reagent. The porous material may or may not be a capillary material. The porous material may contain hydrophilic materials to improve reagent distribution and spreading. This can contribute to the formation of a consistent vapor. Particularly preferred materials will depend on the physical properties of the reagent. The porous material can have any suitable porosity to be used with reagents having different physical properties. Preferably, the capillary wick is in contact with the porous material, as this will provide good reagent transfer.

[0076] The at least one heating element can heat the agent at the second end of the capillary wick by means of conduction. The heating element can at least partially contact the second end of the capillary wick. Alternatively, heat from the heating element can be conducted to the agent at the second end of the capillary wick by means of a heat conduction element. Alternatively, during use, the at least one heating element can transfer heat to the surrounding air drawn through the cylinder, which in turn heats the agent at the second end of the capillary wick by convection. The surrounding air can be heated before passing through the second end of the capillary wick. Alternatively, the surrounding air can be drawn through the second end of the wick and then heated, as described in WO 2007 / 078273 A1.

[0077] A first compartment containing a volatile delivery-enhancing compound may be circumferentially disposed around at least a portion of a second compartment. In such an embodiment, the first compartment may be defined by the outer wall of the second compartment and the outer shell of the cylinder. Alternatively, the first and second compartments may be arranged sequentially along the longitudinal direction of the cylinder, with the first compartment upstream of the second compartment. In such an embodiment, the first and second compartments may be adjacent to each other or may be separated along the longitudinal direction of the cylinder.

[0078] Preferably, the first compartment is substantially sealed before the first use of the cartridge. For example, the first compartment may include one or more seals that can be punctured or otherwise opened upon the first use of the cartridge.

[0079] As described above, the volatile delivery-enhancing compound interacts with the pharmaceutical agent in the gas phase to form pharmaceutical-containing particles. When the volatile delivery-enhancing compound is an acid and the pharmaceutical agent source is a nicotine source, the acid will interact with nicotine in the gas phase to form nicotine salt particles. Preferably, the median aerodynamic diameter of the nicotine salt particles is less than about 6 micrometers. The median aerodynamic diameter of the nicotine salt particles may be less than about 1 micrometer. Preferably, the median aerodynamic diameter of the nicotine salt particles is between about 0.5 micrometers and about 5 micrometers.

[0080] The cartridge may further include a third compartment. Preferably, the third compartment is downstream of the second compartment. When the cartridge includes an aerosol forming chamber, the third compartment is preferably downstream of the aerosol forming chamber. The third compartment may include a fragrance source. Optionally or additionally, the third compartment may include a filter material capable of removing at least a portion of any unreacted volatile delivery-enhancing compounds mixed with aerosolized drug-containing particles inhaled through the third compartment. The filter material may include an adsorbent, such as activated carbon. As will be understood, any number of additional compartments may be provided as needed. For example, the cartridge may include a third compartment containing filter material and a fourth compartment containing a fragrance source downstream of the third compartment.

[0081] Preferably, the cartridge comprises an opaque outer shell. This advantageously reduces the risk of degradation of volatile delivery-enhancing compounds and agents due to light exposure.

[0082] According to another aspect of the invention, an apparatus configured to receive a cylinder as described herein is provided. The apparatus includes: a housing; a power source; a temperature control device for controlling the temperature of a first compartment of the cylinder; and electronic circuitry configured to control power from the power source to the control device; wherein the electronic circuitry is configured to maintain the first compartment of the cylinder at a temperature between approximately 30°C and approximately 50°C.

[0083] In a preferred embodiment, the control measures include a heater to heat the first compartment of the cylinder.

[0084] Such a device, when used in combination with the cartridge according to the invention, advantageously allows for more consistent aerosol generation and drug delivery with each draw. By constructing the device to maintain the first compartment of the cartridge at a temperature between about 30°C and about 50°C, the effects of environmental conditions on aerosol generation and drug delivery with each draw can be mitigated.

[0085] Optionally or additionally, the device may include a heater to heat the ambient air to a temperature between about 30°C and about 50°C before it is drawn into the first compartment of the cylinder.

[0086] According to another aspect of the invention, an aerosol delivery system is provided. The aerosol delivery system includes: a device as described herein, cooperating with a cartridge as described herein. The device or cartridge includes a first compartment containing a volatile delivery-enhancing compound. The device or cartridge includes a second compartment containing a drug source. The device or cartridge includes an evaporator for heating the drug. The device or cartridge further includes a transfer element for transferring the drug from the second compartment to the evaporator. The device or cartridge further includes an aerosol-forming chamber in fluid communication with the first and second compartments. In use, the drug reacts with the volatile delivery-enhancing compound in the aerosol-forming chamber in the gas phase to form atomized drug-containing particles.

[0087] Preferably, the device or cylinder further includes a nozzle in fluid communication with the aerosol forming chamber. Preferably, the nozzle is part of the cylinder.

[0088] The nozzle can contain any suitable material or combination of materials. Examples of suitable materials include thermoplastic materials suitable for food or pharmaceutical applications, such as polypropylene, polyetheretherketone (PEEK), and polyethylene.

[0089] Preferably, the cartridge is non-refillable. Therefore, the cartridge should be replaced when the medicine in the second compartment is depleted.

[0090] In some embodiments, the device and the cylinder may be disposable.

[0091] Advantageously, when changing the cartridge, all components of the device that may come into contact with volatile delivery-enhancing compounds or agents are replaced. This avoids any cross-contamination between different nozzles and different cartridges in the device, such as cartridges containing different volatile delivery-enhancing compounds or agents.

[0092] This design advantageously protects the agent in the second compartment from exposure to oxygen (since oxygen typically cannot enter the second compartment via the capillary wick or other transfer elements) and, in some embodiments, from exposure to light, thereby significantly reducing the risk of agent degradation. Consequently, a high level of hygiene can be maintained. Furthermore, the risk of the evaporator becoming clogged with the agent can be advantageously and significantly reduced by replacing the cartridge at appropriate intervals.

[0093] In a preferred embodiment, the evaporator includes an electrically operated heater that can be connected to a power source in the device. When the device and the cartridge are connected, the heater in the cartridge is electrically connected to a power source via a circuit arranged to provide power to the heater in the cartridge. In one embodiment, power is provided to the heater in the cartridge when the user activates the switch. In this embodiment, power is then provided to the heater in the cartridge substantially continuously for a fixed period of time. Preferably, the power source has sufficient power to provide power to the heater in the cartridge for at least about 4 minutes, preferably at least about 5 minutes, and more preferably about 6 minutes. The average duration of a single smoking session has been found to be approximately 6 minutes.

[0094] Preferably, the power source contains sufficient power to allow the user to take approximately 200 to approximately 500 puffs.

[0095] In an alternative embodiment, power is supplied to the heater in the cartridge only when the user takes a puff. Preferably, the circuitry includes a sensor to detect an airflow indicating that the user has taken a puff. The sensor may be an electromechanical device. Alternatively, the sensor may be any of the following: a mechanical device, an optical device, an opto-mechanical device, and a microelectromechanical system (MEMS) based sensor. In such an embodiment, the electronic circuitry is preferably arranged to provide a pulse of current to the heater in the cartridge when the sensor detects that the user has taken a puff. Preferably, the time period of the current pulse is preset according to the amount of nicotine formulation to be evaporated. For this purpose, the electronic circuitry is preferably programmable.

[0096] Alternatively, the electronic circuitry may include a manually operable switch to allow the user to initiate a puff. In such an embodiment, the time period of the current pulses sent to the heater in the cartridge when the user manually operates the switch is preferably preset according to the amount of nicotine formulation to be evaporated. For this purpose, the electronic circuitry is preferably programmable.

[0097] Preferably, the power source includes a battery contained in the device. The power source may be a lithium-ion battery or a variant thereof, such as a lithium-ion polymer battery. Alternatively, the power source may be a nickel-metal hydride battery, a nickel-cadmium battery, or a fuel cell.

[0098] The power source may include circuitry that can be charged by an external charging component. In this case, it is preferable that the circuitry provides power for a predetermined number of pumps while already charged, after which the circuitry must be reconnected to the external charging component. Examples of suitable circuitry include one or more capacitors or rechargeable batteries.

[0099] Preferably, the device and the cylinder are arranged to lock together in a releasable manner when connected.

[0100] The housing of the device may be formed from any suitable material or combination of materials. Examples of suitable materials include, but are not limited to, metals, alloys, plastics, or composite materials containing one or more of these materials. Preferably, the housing is lightweight and non-brittle.

[0101] Aerosol delivery systems and devices are preferably portable. Aerosol delivery systems may have a size and shape comparable to conventional smoking products such as cigars or cigarettes.

[0102] According to another aspect of the invention, a method is provided for delivering aerosolized drug-containing particles to a user. The method includes: controlling the temperature of a volatile delivery-enhancing compound to between about 30°C and about 50°C to form a vapor containing the delivery-enhancing compound; heating a drug source to a temperature between about 70°C and about 100°C to form a drug-containing vapor; and contacting the vapor containing the delivery-enhancing compound with the drug-containing vapor to form aerosolized drug-containing particles.

[0103] In a preferred embodiment, the step of controlling the temperature of the delivery enhancement compound may include heating the delivery enhancement compound.

[0104] As should be understood, several factors influence the formation of drug-containing particles. Generally, to control drug delivery, it is important to control the evaporation of the drug and the volatile delivery-enhancing compound. It is also important to control the relative amounts of the drug and the volatile delivery-enhancing compound. In a preferred embodiment where the volatile delivery-enhancing compound is an acid and the drug source is a nicotine source, the molar ratio of acid to nicotine in the aerosol forming chamber is approximately 1:1. For the equivalent power supplied to the evaporator, it has been found that using an acid or ammonium chloride as the delivery-enhancing compound approximately doubles the rate of nicotine delivery to the user.

[0105] The evaporation of the volatile delivery-enhancing compound is controlled by the concentration of the volatile delivery-enhancing compound in the first compartment and the exchange surface area of ​​the volatile delivery-enhancing compound in the first compartment. The evaporation of the volatile delivery-enhancing compound can be controlled by heating the first compartment of the cylinder or by heating the ambient air before it passes through the first compartment of the cylinder. In a preferred embodiment where the first compartment contains pyruvate, approximately 60 micrograms of pyruvate are preferably evaporated per puff.

[0106] The evaporation of the reagent can be controlled by the power supplied to the evaporator and by the nature of the transfer element used to transfer the reagent to the evaporator.

[0107] Preferably, the nicotine source is a nicotine source, and the power supplied to the vaporizer is between about 0.1W and about 0.2W to produce optimal nicotine delivery of about 100 micrograms per puff to the user. More preferably, the power supplied to the heater is between about 0.13W and about 0.14W.

[0108] In commercially available electronic cigarettes, the power supplied to the vaporizer is typically much higher; in some cases, measurements show a power consumption between approximately 3.7W and approximately 5W. The reduction in power consumption in the aerosol delivery system and device according to the invention is therefore significant compared to such electronic cigarettes. Furthermore, the operating temperature of the vaporizer in the aerosol delivery system and device according to the invention can be reduced to approximately 80°C to approximately 100°C, compared to approximately 200°C to approximately 300°C in commercially available electronic cigarettes.

[0109] To avoid ambiguity, the features described above with respect to one aspect of the invention are also applicable to other aspects of the invention. In particular, the features described above with respect to the cylinders, devices, and aerosol delivery systems according to the invention are also applicable, where appropriate, to the methods according to the invention, and vice versa. Attached Figure Description

[0110] Exemplary embodiments of the present invention are described below with reference to the accompanying drawings, in which:

[0111] Figures 1(a)-(d) illustrate embodiments of the aerosol delivery system according to the present invention; and

[0112] Figure 2 A detailed view of the outer shell of the cylinder according to an embodiment of the present invention is shown. Detailed Implementation

[0113] Figure 1(a) shows an aerosol delivery system 100 having the general size and shape of a conventional smoking product such as a cigar or cigarette. The aerosol delivery system 100 includes a device 102, a cartridge 104, and a mouthpiece 106. The mouthpiece 106 forms part of the cartridge 104. The cartridge 104 includes an air inlet 108 located upstream of the mouthpiece and an air outlet 110 at the mouthpiece tip of the mouthpiece 106. A switch 112 is provided on the device.

[0114] Figure 1(b) shows a cross-sectional view of the aerosol delivery system 100, illustrating further details of the device 102 and the cartridge 104. The cartridge 104 includes a first compartment 114 containing pyruvate and a second compartment 116 containing a liquid nicotine formulation. As shown in Figure 1(b), the first compartment 114 is circumferentially disposed around the second compartment 116 and is defined by the outer peripheral surface of the second compartment 116 and the inner peripheral surface of the outer shell 118 of the cartridge 104.

[0115] As shown in Figure 1(c), the first compartment 114 includes a porous plug on which pyruvate is adsorbed. The cylinder 104 also includes a capillary wick 122 having a first end within the second compartment 116 and a second end outside the second compartment. The capillary wick 122 is configured to deliver a liquid nicotine formulation from the second compartment 116 to an evaporator surrounding the second end of the capillary wick 122. The evaporator includes an electric heater. An aerosol forming chamber 124 is disposed downstream of the second compartment 116 in a nozzle 106. The nozzle 106 may include a third compartment (not shown) containing filter material.

[0116] The device 102 includes a power source 126 in the form of a rechargeable battery. The device 102 also includes electronic circuitry 128 configured to control the power supply from the power source 126 to the evaporator. The device 102 also includes a heater (not shown) configured to heat the first compartment 114 of the cylinder 104.

[0117] Figure 1(c) shows an aerosol delivery system 100 with its components separated. The aerosol delivery system 100 is configured such that the cartridge 104 is disposable and can be detached from and replaced by the device 102. A coupling 130 is provided to allow the cartridge 104 to be coupled to the device 102. The coupling 130 includes a male threaded portion on the device 102 and a female threaded portion on the cartridge 104. The coupling 130 also includes an electrical connector (not shown) that allows power to be supplied to the evaporator. Figure 1(d) shows an alternative view of the aerosol delivery system shown in Figure 1(c).

[0118] In use, the user inhales through the mouthpiece 106, drawing air into the cylinder 104 through the air inlet 108 in the housing 118, downstream through the cylinder 104, and then out through the air outlet 110 in the mouthpiece 106 into the user's mouth. Air enters the first compartment 114 and passes through a porous plug made of fibrous material 120 on which pyruvate is adsorbed, trapping pyruvate vapor. To achieve consistent pyruvate vapor generation, the first compartment is heated to approximately 40°C by a heater in the device. Alternatively, the heater may heat the air drawn into the cylinder 104 through the air inlet 108 in the housing 118 before it passes through the first compartment 114. The airflow exiting the first compartment 114 and subsequently passing through the evaporator is a pyruvate-containing airflow.

[0119] A suction detection sensor (not shown) is provided in communication with electronic circuitry 28. When a suction is detected, the electronic circuitry activates the vaporizer to evaporate the liquid nicotine formulation. A stream of air containing pyruvate and the evaporated nicotine formulation are drawn downstream into the aerosol forming chamber 124. The pyruvate and nicotine interact in the gas phase within the aerosol forming chamber 124 to form nicotine salt particles with a median aerodynamic particle size between approximately 0.5 micrometers and approximately 5 micrometers. The atomized nicotine salt particles are drawn out of the suction cartridge 104 through the air outlet 110 in the mouthpiece 106 and into the user's mouth. The aerosol delivery system 100 is configured to deliver approximately 100 micrograms of nicotine to the user per puff. The electronic circuitry is configured to provide approximately 0.14 W of power to the vaporizer for each puff.

[0120] Any unreacted pyruvate can be removed from the nicotine salt particulate aerosol through the filter material in the third compartment of nozzle 106.

[0121] The first compartment 116 is configured to hold approximately 150 microliters of pyruvate, and the second compartment is configured to hold approximately 100 microliters of liquid nicotine. The power source 126 provides sufficient power to allow approximately 200 to 500 puffs before recharging is required. The volumes of the first and second compartments are sufficient to allow another 200 to 500 puffs before cartridge replacement is needed. Each puff releases approximately 100 micrograms of nicotine and approximately 60 micrograms of pyruvate. To optimize the interaction between nicotine and pyruvate, a molar ratio of approximately 1:1 is preferred.

[0122] Figure 2 A detailed view of cylinder 200 is shown, which includes a first compartment and a second compartment; the configuration shown is an alternative embodiment to those shown in Figures 1(a)-(d). For simplicity, the outer shell of the cylinder has been... Figure 2 Omitted. Figure 2An airflow path through the cylinder is also shown. As can be seen, the cylinder 200 includes a first compartment 202 that circumferentially surrounds a portion of a second compartment 116. The second end of the capillary wick 204 is constrained by an electric heater 206. The electric heater 206 is in the form of a long filament wound around the capillary wick 204. Arrow 208 shows the airflow path from the air inlet through the first compartment 202 and through the capillary wick 204. An electrical contact 210 is provided to connect the electric heater 206 to a power source (not shown) in the device.

[0123] Examples of discontinuous heating of nicotine

[0124] To avoid nicotine loss between puffs and to simulate the puff detection system, the standard Health Canada smoking method is adopted (puff volume 55ml, puff duration 2 seconds, time interval between puffs 30 seconds) and the signal from the PDSP pump is used during the 2-second puff to drive the nicotine heating / evaporation via the power supply unit.

[0125] In the following experiment, preparation Figure 1b The aerosol delivery system is shown in the figure. A cartridge comprising a capillary wick and a heating wire was filled with pure nicotine, while a porous plug (Porex XMF-0507) saturated with 150 µl of pyruvate was positioned upstream of the inhalation flow. Five 30-puff smoking trials were conducted using a heating power gradually increasing from 0 to 0.2 W. Deliveries from the 30-puff groups were collected on Cambridge filters, and nicotine and pyruvate were analyzed. The results are shown in the table below:

[0126] Since the pyruvate stopper was not heated (maintained at a laboratory temperature of 22°C), pyruvate delivery was relatively constant, while nicotine delivery increased with increasing heating power. In the setup of this experiment, the optimal equimolar ratio of nicotine was obtained when heated between 0.1 W and 0.15 W.

[0127] This experiment confirms that very low power heating requirements (compared to conventional e-cigarettes) provide the necessary amount of ingredients to be delivered to the consumer within the aerosol forming chamber.

Claims

1. A cylinder, the cylinder comprising: A first compartment containing a source of volatile delivery-enhancing compounds; The second compartment contains the drug source; An evaporator for heating the pharmaceutical agent; and For transferring the agent from the second compartment to the evaporator The transfer element.

2. The cylinder according to claim 1, wherein the cylinder further comprises an aerosol forming chamber in fluid communication with the first compartment and the second compartment.

3. The cylinder of claim 2, further comprising at least one air inlet upstream of the first compartment and at least one air outlet downstream of the aerosol forming chamber, the at least one air inlet and the at least one air outlet being arranged to define an airflow path extending from the at least one air inlet via the first compartment, the evaporator and the aerosol forming chamber to the at least one air outlet.

4. The cylinder according to claim 1, 2 or 3, wherein the transfer element comprises capillary material to transfer the agent from the second compartment to the evaporator by capillary action.

5. The cylinder according to claim 4, wherein the capillary material is a capillary core having a first portion extending into the second compartment and a second portion adjacent to the evaporator.

6. The tube according to any one of the preceding claims, wherein the second compartment includes an adsorption element thereon on which the agent is adsorbed.

7. The cartridge according to any one of the preceding claims, wherein the pharmaceutical agent comprises pure nicotine, a nicotine solution, or a liquid tobacco extract.

8. The tube according to any one of the preceding claims, wherein the first compartment includes an adsorption element to which the volatile delivery enhancement compound is adsorbed.

9. The cartridge according to any one of the preceding claims, wherein the volatile delivery-enhancing compound comprises an acid selected from 3-methyl-2-oxovalerate, pyruvate, 2-oxovalerate, 4-methyl-2-oxovalerate, 3-methyl-2-oxobutyric acid, 2-oxooctanoic acid, and combinations thereof.

10. The cylinder according to any one of the preceding claims, wherein the evaporator includes an electrically operated heater that can be connected to a power source.

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