Liquid nicotine formulation

Abstract

To provide liquid nicotine formulation and a cartridge for use in an aerosol-generating system, and the aerosol-generating system.SOLUTION: There is provided a liquid nicotine formulation comprising: one or more water-miscible solvents; one or more water-immiscible solvents having a water solubility at 20°C of about 100 mg / mL or less; and one or more water-soluble organic acids, wherein the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or more. There is provided a liquid nicotine formulation comprising: one or more water-miscible solvents; one or more water-immiscible solvents having a partition coefficient (log P) at 20°C of about 0.05 or more; and one or more water-soluble organic acids, wherein the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or more. There is provided a cartridge that accommodates the liquid nicotine formulation. There is provided an aerosol-generating system comprising the liquid nicotine formulation and an atomiser configured to generate an aerosol from the liquid nicotine formulation.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a liquid nicotine formulation for use in an aerosol generation system. The present invention also relates to a cartridge for an aerosol generation system containing a liquid nicotine formulation, and to an aerosol generation system comprising a liquid nicotine formulation and an atomizer configured to generate an aerosol from the liquid nicotine formulation. [Background technology]

[0002] Aerosol generation systems for delivering nicotine to a user are known that include an atomizer configured to generate an inhalable aerosol from a liquid nicotine formulation. Some known aerosol generation systems include a thermal atomizer, such as an electric heater, configured to heat and vaporize the liquid nicotine formulation to generate an aerosol. Other known aerosol generation systems include a non-thermal atomizer configured to generate an aerosol from the liquid nicotine formulation, for example using impinging jet, ultrasonic, or vibrating mesh technology.

[0003] In such aerosol generation systems, efficient pulmonary delivery of the inhalable aerosol generated from a liquid nicotine formulation is considered to be an important criterion for user preference and satisfaction. A typical liquid nicotine formulation for use in an aerosol generation system contains glycerin, propylene glycol, and water as solvents. Summary of the Invention [Problem to be solved by the invention]

[0004] It would be desirable to provide a liquid nicotine formulation for use in an aerosol generation system enabling the generation of an aerosol that provides a user with improved nicotine satisfaction compared to such typical liquid nicotine formulations. In particular, it would be desirable to provide a liquid nicotine formulation for use in an aerosol generation system enabling the generation of an aerosol that provides a user with nicotine satisfaction similar to that of tobacco smoke generated by the combustion of a conventional cigarette. [Means for solving the problem]

[0005] According to a first aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0006] According to a first aspect of the invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0007] According to a first aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0008] According to a second aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0009] According to a second aspect of the invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0010] According to a second aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0011] As used herein in connection with the present invention, the term "liquid nicotine formulation" refers to a liquid formulation comprising nicotine.

[0012] As used herein in connection with the present invention, the term "nicotine" refers to nicotine, nicotine base, or nicotine salt. In embodiments where the liquid nicotine formulation comprises nicotine base or nicotine salt, the amount of nicotine recited herein is the amount of free base nicotine or the amount of protonated nicotine, respectively.

[0013] As used herein in connection with the present invention, the term "water-miscible solvent" refers to a compound, other than water or an organic acid, that is liquid at 20° C. and that will mix with water in all proportions to form a homogeneous solution.

[0014] As used herein in connection with the present invention, the term "water-soluble organic acid" refers to an organic acid that has a water solubility of about 500 mg / mL or greater at 20°C.

[0015] Unless otherwise stated, the water solubility values ​​listed herein are the water solubilities measured based on the preliminary test of OECD (1995), Test No. 105: Water Solubility, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264069589-en. In the stepwise procedure, increasing volumes of distilled water are added to 0.1 g of sample (solid substances must be crushed) in a 10 mL glass stoppered graduated cylinder at 20°C. However, if the substance is an acid, the sample is added to the distilled water in the first step. After each addition of a certain amount of water, the mixture is shaken for 10 minutes and the sample is visually checked for any undissolved parts. If the sample or part of the sample remains undissolved after the addition of 10 mL of water, the experiment is continued in the 100 mL graduated cylinder. Approximate solubilities are provided in Table 1 below, below, in the volume of water below which complete dissolution of the sample occurs.

[0016] If the solubility is low, it may take a long time to dissolve the substance, which should be allowed to take at least 24 hours. If after 24 hours the substance is still not dissolved, the graduated cylinder is placed in an ultrasonic bath at 40°C for 15 minutes and allowed to take another 24 hours (maximum 96 hours). If the substance is still not dissolved, it is considered to be below the solubility limit or not soluble. [Table 1] Table 1

[0017] As used herein in relation to the first aspect of the invention, the term "water-immiscible solvent" refers to a compound that is liquid at 20°C and has a water solubility of about 100 mg / mL or less at 20°C.

[0018] As used herein in relation to the second aspect of the invention, the term "water-immiscible solvent" refers to a compound that is liquid at 20°C and has a partition coefficient (log P) of about 0.05 or greater at 20°C.

[0019] Unless otherwise stated, the partition coefficient (log P) values ​​listed herein are the octanol / water partition coefficients (log P OW ), which is based on OECD (1995), Test No. 107: Partition coefficient (n-octanol / water): Shake flask method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264069626-en (log P in the range of -2 to 4) OW values), OECD (2004), Test No. 117: Partition coefficient (n-octanol / water), HPLC method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264069824-en (log P values ​​in the range 0–6) OW values), and OECD (2006), Test No. 123: Partition coefficient (1-octanol / water): slow stirring method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264015845-en (log P values ​​in the range up to 8.2 OW The value is measured according to the

[0020] The inclusion of a combination of one or more water-miscible solvents, one or more water-immiscible solvents, and one or more water-soluble organic acids in a liquid nicotine formulation according to the invention advantageously allows for the generation of an inhalable aerosol that provides the user with improved nicotine satisfaction compared to typical liquid nicotine formulations. Specifically, as discussed further below, the inclusion of a combination of one or more water-miscible solvents, one or more water-immiscible solvents, and one or more water-soluble organic acids in a liquid nicotine formulation according to the invention advantageously allows for the generation of an inhalable aerosol that has improved nicotine retention characteristics compared to typical liquid nicotine formulations.

[0021] Tobacco smoke generated by the combustion of conventional cigarettes contains thousands of different smoke components. Surprisingly, it has been found that the inclusion of a combination of one or more water-miscible solvents, one or more water-immiscible solvents, and one or more water-soluble organic acids in a liquid nicotine formulation according to the present invention advantageously allows for the generation of an inhalable aerosol having nicotine retention properties similar to those of tobacco smoke generated by the combustion of conventional cigarettes.

[0022] Unless otherwise stated, the weight percentages of the components of the liquid nicotine formulations listed herein are based on the total weight of the liquid nicotine formulation.

[0023] The liquid nicotine formulation may contain natural or synthetic nicotine.

[0024] The liquid nicotine formulation may have a nicotine content of about 0.5 weight percent or greater.

[0025] It is preferred that the liquid nicotine formulation have a nicotine content of about 1 weight percent or greater. More preferred that the liquid nicotine formulation have a nicotine content of about 1.5 weight percent or greater.

[0026] The liquid nicotine formulation may have a nicotine content of about 10 percent by weight or less.The liquid nicotine formulation may have a nicotine content of about 8 percent by weight or less.

[0027] It is preferred that the liquid nicotine formulation have a nicotine content of about 5 weight percent or less. More preferred that the liquid nicotine formulation have a nicotine content of about 3 weight percent or less.

[0028] The liquid nicotine formulation may have a nicotine content of about 0.5 weight percent to about 10 weight percent. For example, the liquid nicotine formulation may have a nicotine content of about 0.5 weight percent to about 8 weight percent, about 0.5 weight percent to about 5 weight percent, or about 0.5 weight percent to about 3 weight percent.

[0029] It is preferred that the liquid nicotine formulation has a nicotine content of about 1 weight percent to about 10 weight percent. For example, the liquid nicotine formulation may have a nicotine content of about 1 weight percent to about 8 weight percent, about 1 weight percent to about 5 weight percent, or about 1 weight percent to about 3 weight percent.

[0030] More preferably, the liquid nicotine formulation has a nicotine content of about 1.5 weight percent to about 10 weight percent. For example, the liquid nicotine formulation may have a nicotine content of about 1.5 weight percent to about 8 weight percent, about 1.5 weight percent to about 5 weight percent, or about 1.5 weight percent to about 3 weight percent.

[0031] The liquid nicotine formulation comprises one or more water-miscible solvents, which may advantageously serve to dissolve and stabilize the polar and ionic components of the liquid nicotine formulation.

[0032] It is preferred that the liquid nicotine formulation has a water-miscible solvent content of about 5 weight percent or more. It is more preferred that the liquid nicotine formulation has a water-miscible solvent content of about 10 weight percent or more. For example, the liquid nicotine formulation may have a water-miscible solvent content of about 15 weight percent or more, about 20 weight percent or more, or about 25 weight percent or more.

[0033] The liquid nicotine formulation may have a water-miscible solvent content of about 80 percent by weight or less, or about 75 percent by weight or less.

[0034] It is preferred that the liquid nicotine formulation has a water-miscible solvent content of about 70 weight percent or less. More preferably, the liquid nicotine formulation has a water-miscible solvent content of about 60 weight percent or less. For example, the liquid nicotine formulation may have a water-miscible solvent content of about 50 weight percent or less or about 40 weight percent or less.

[0035] It is preferred that the liquid nicotine formulation has a water-miscible solvent content of about 5 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a water-miscible solvent content of about 5 weight percent to about 60 weight percent, about 5 weight percent to about 50 weight percent, or about 5 weight percent to about 40 weight percent.

[0036] More preferably, the liquid nicotine formulation has a water-miscible solvent content of about 10 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a water-miscible solvent content of about 10 weight percent to about 60 weight percent, about 10 weight percent to about 50 weight percent, or about 10 weight percent to about 40 weight percent.

[0037] The liquid nicotine formulation may have a water-miscible solvent content of about 15 weight percent to about 70 weight percent, about 15 weight percent to about 60 weight percent, about 15 weight percent to about 50 weight percent, or about 15 weight percent to about 40 weight percent.

[0038] The liquid nicotine formulation may have a water-miscible solvent content of about 20 percent to about 70 percent by weight, about 20 percent to about 60 percent by weight, about 20 percent to about 50 percent by weight, or about 20 percent to about 40 percent by weight.

[0039] The liquid nicotine formulation may have a water-miscible solvent content of about 25 percent to about 70 percent by weight, about 25 percent to about 60 percent by weight, about 25 percent to about 50 percent by weight, or about 25 percent to about 40 percent by weight.

[0040] Preferably, the one or more water-miscible solvents are one or more water-miscible polyhydric alcohols.

[0041] As used herein in connection with the present invention, the term "water-miscible polyhydric alcohol" refers to a polyhydric alcohol that is liquid at 20° C. and that will mix with water in all proportions to form a homogeneous solution.

[0042] According to a preferred embodiment of the first aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising one or more water-miscible polyalcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0043] According to a preferred embodiment of the first aspect of the present invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising one or more water-miscible polyalcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0044] According to a preferred embodiment of the first aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising one or more water-miscible polyalcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0045] According to a preferred embodiment of the second aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0046] According to a preferred embodiment of the second aspect of the present invention, there is also provided a cartridge for use in an aerosol generating system, the cartridge containing a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0047] According to a preferred embodiment of the second aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0048] It is preferred that the liquid nicotine formulation has a water-miscible polyhydric alcohol content of about 5 weight percent or more.It is more preferred that the liquid nicotine formulation has a water-miscible polyhydric alcohol content of about 10 weight percent or more.For example, the liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 15 weight percent or more, about 20 weight percent or more, or about 25 weight percent or more.

[0049] The liquid nicotine formulation may have a water-miscible polyalcohol content of about 80 percent by weight or less, or about 75 percent by weight or less.

[0050] It is preferred that the liquid nicotine formulation has a water-miscible polyhydric alcohol content of about 70 weight percent or less. More preferably, the liquid nicotine formulation has a water-miscible polyhydric alcohol content of about 60 weight percent or less. For example, the liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 50 weight percent or less or about 40 weight percent or less.

[0051] It is preferred that the liquid nicotine formulation has a water-miscible polyhydric alcohol content of about 5 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 5 weight percent to about 60 weight percent, about 5 weight percent to about 50 weight percent, or about 5 weight percent to about 40 weight percent.

[0052] More preferably, the liquid nicotine formulation has a water-miscible polyhydric alcohol content of about 10 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 10 weight percent to about 60 weight percent, about 10 weight percent to about 50 weight percent, or about 10 weight percent to about 40 weight percent.

[0053] The liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 15 weight percent to about 70 weight percent, about 15 weight percent to about 60 weight percent, about 15 weight percent to about 50 weight percent, or about 15 weight percent to about 40 weight percent.

[0054] The liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 20 percent to about 70 percent by weight, about 20 percent to about 60 percent by weight, about 20 percent to about 50 percent by weight, or about 20 percent to about 40 percent by weight.

[0055] The liquid nicotine formulation may have a water-miscible polyhydric alcohol content of about 25 percent to about 70 percent by weight, about 25 percent to about 60 percent by weight, about 25 percent to about 50 percent by weight, or about 25 percent to about 40 percent by weight.

[0056] Preferably, the one or more water-miscible polyhydric alcohols are selected from the group consisting of 1,3-butanediol, glycerin, propylene glycol, and triethylene glycol.

[0057] More preferably, the one or more water-miscible polyhydric alcohols are selected from the group consisting of glycerin and propylene glycol.

[0058] Most preferably, the one or more water-miscible polyhydric alcohols are selected from the group consisting of vegetable glycerin and propylene glycol.

[0059] According to a preferred embodiment of the first aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0060] According to a preferred embodiment of the first aspect of the present invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0061] According to a preferred embodiment of the first aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0062] According to a preferred embodiment of the second aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0063] According to a preferred embodiment of the second aspect of the present invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0064] According to a preferred embodiment of the second aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0065] It is preferred that the liquid nicotine formulation has a combined glycerin and propylene glycol content of about 5 weight percent or more.It is more preferred that the liquid nicotine formulation has a combined glycerin and propylene glycol content of about 10 weight percent or more.For example, the liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 15 weight percent or more, about 20 weight percent or more, or about 25 weight percent or more.

[0066] The liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 80 percent by weight or less, or about 75 percent by weight or less.

[0067] It is preferred that the liquid nicotine formulation has a combined glycerin and propylene glycol content of about 70 weight percent or less.More preferably, the liquid nicotine formulation has a combined glycerin and propylene glycol content of about 60 weight percent or less.For example, the liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 50 weight percent or less or about 40 weight percent or less.

[0068] It is preferred that the liquid nicotine formulation has a combined glycerin and propylene glycol content of about 5 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 5 weight percent to about 60 weight percent, about 5 weight percent to about 50 weight percent, or about 5 weight percent to about 40 weight percent.

[0069] More preferably, the liquid nicotine formulation has a combined glycerin and propylene glycol content of about 10 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 10 weight percent to about 60 weight percent, about 10 weight percent to about 50 weight percent, or about 10 weight percent to about 40 weight percent.

[0070] The liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 15 weight percent to about 70 weight percent, about 15 weight percent to about 60 weight percent, about 15 weight percent to about 50 weight percent, or about 15 weight percent to about 40 weight percent.

[0071] The liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 20 weight percent to about 70 weight percent, about 20 weight percent to about 60 weight percent, about 20 weight percent to about 50 weight percent, or about 20 weight percent to about 40 weight percent.

[0072] The liquid nicotine formulation may have a combined glycerin and propylene glycol content of about 25 weight percent to about 70 weight percent, about 25 weight percent to about 60 weight percent, about 25 weight percent to about 50 weight percent, or about 25 weight percent to about 40 weight percent.

[0073] It is preferred that the liquid nicotine formulation have a glycerin content of about 5 weight percent or greater.

[0074] More preferably, the liquid nicotine formulation has a glycerin content of about 6 weight percent or more. For example, the liquid nicotine formulation may have a glycerin content of about 7 weight percent or more or about 8 weight percent or more.

[0075] The liquid nicotine formulation may have a glycerin content of about 80 percent by weight or less, or about 75 percent by weight or less.

[0076] It is preferred that the liquid nicotine formulation has a glycerin content of about 70 weight percent or less. It is more preferred that the liquid nicotine formulation has a glycerin content of about 60 weight percent or less. For example, the liquid nicotine formulation may have a glycerin content of about 50 weight percent or less or about 40 weight percent or less.

[0077] It is preferred that the liquid nicotine formulation has a glycerin content of about 5 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a glycerin content of about 5 weight percent to about 60 weight percent, about 5 weight percent to about 50 weight percent, or about 5 weight percent to about 40 weight percent.

[0078] More preferably, the liquid nicotine formulation has a glycerin content of about 6 weight percent to about 70 weight percent. For example, the liquid nicotine formulation may have a glycerin content of about 6 weight percent to about 60 weight percent, about 6 weight percent to about 50 weight percent, or about 6 weight percent to about 40 weight percent.

[0079] The liquid nicotine formulation may have a glycerin content of about 7 percent to about 70 percent by weight, about 7 percent to about 60 percent by weight, about 7 percent to about 50 percent by weight, or about 7 percent to about 40 percent by weight.

[0080] The liquid nicotine formulation may have a glycerin content of about 8 percent to about 70 percent by weight, about 8 percent to about 60 percent by weight, about 8 percent to about 50 percent by weight, or about 8 percent to about 40 percent by weight.

[0081] Preferably, the liquid nicotine formulation comprises water and one or more water-miscible solvents.

[0082] According to a preferred embodiment of the first aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0083] According to a preferred embodiment of the first aspect of the present invention, there is also provided a cartridge for use in an aerosol generating system, the cartridge containing a liquid nicotine formulation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0084] According to a preferred embodiment of the first aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility at 20° C. of about 100 mg / mL or less, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0085] According to a preferred embodiment of the second aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0086] According to a preferred embodiment of the second aspect of the present invention, there is also provided a cartridge for use in an aerosol generating system, the cartridge containing a liquid nicotine formulation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0087] According to a preferred embodiment of the second aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0088] In combination, water and one or more water-miscible solvents can advantageously help to dissolve and stabilize the polar and ionic components of the liquid nicotine formulation.

[0089] The liquid nicotine formulation may have a water content of about 5 percent by weight or greater.

[0090] It is preferred that the liquid nicotine formulation has a water content of about 10 weight percent or more. It is more preferred that the liquid nicotine formulation has a water content of about 15 weight percent or more. It is most preferred that the liquid nicotine formulation has a water content of about 20 weight percent or more. For example, the liquid nicotine formulation may have a water content of about 25 weight percent or more, about 30 weight percent or more, or about 35 weight percent or more.

[0091] It is preferred that the liquid nicotine formulation has a water content of about 90 weight percent or less. It is more preferred that the liquid nicotine formulation has a water content of about 85 weight percent or less. For example, the liquid nicotine formulation may have a water content of about 80 weight percent or less, about 75 weight percent or less, about 70 weight percent or less, or about 65 weight percent or less.

[0092] The liquid nicotine formulation may have a water content of about 5 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 5 weight percent to about 85 weight percent, about 5 weight percent to about 80 weight percent, about 5 weight percent to about 75 weight percent, about 5 weight percent to about 70 weight percent, or about 5 weight percent to about 65 weight percent.

[0093] It is preferred that the liquid nicotine formulation has a water content of about 10 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 10 weight percent to about 85 weight percent, about 10 weight percent to about 80 weight percent, about 10 weight percent to about 75 weight percent, about 10 weight percent to about 70 weight percent, or about 10 weight percent to about 65 weight percent.

[0094] It is more preferred that the liquid nicotine formulation has a water content of about 15 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 15 weight percent to about 85 weight percent, about 15 weight percent to about 80 weight percent, about 15 weight percent to about 75 weight percent, about 15 weight percent to about 70 weight percent, or about 15 weight percent to about 65 weight percent.

[0095] Most preferably, the liquid nicotine formulation has a water content of about 20 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 20 weight percent to about 85 weight percent, about 20 weight percent to about 80 weight percent, about 20 weight percent to about 75 weight percent, about 20 weight percent to about 70 weight percent, or about 20 weight percent to about 65 weight percent.

[0096] The liquid nicotine formulation may have a water content of about 25 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 25 weight percent to about 85 weight percent, about 25 weight percent to about 80 weight percent, about 25 weight percent to about 75 weight percent, about 25 weight percent to about 70 weight percent, or about 25 weight percent to about 65 weight percent.

[0097] The liquid nicotine formulation may have a water content of about 30 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 30 weight percent to about 85 weight percent, about 30 weight percent to about 80 weight percent, about 30 weight percent to about 75 weight percent, about 30 weight percent to about 70 weight percent, or about 30 weight percent to about 65 weight percent.

[0098] The liquid nicotine formulation may have a water content of about 35 weight percent to about 90 weight percent. For example, the liquid nicotine formulation may have a water content of about 35 weight percent to about 85 weight percent, about 35 weight percent to about 80 weight percent, about 35 weight percent to about 75 weight percent, about 35 weight percent to about 70 weight percent, or about 35 weight percent to about 65 weight percent.

[0099] The liquid nicotine formulation may have a combined water and water-miscible solvent content of about 50 weight percent or more, about 55 weight percent or more, about 60 weight percent or more, about 65 weight percent or more, or about 70 weight percent or more.

[0100] It is preferred that the liquid nicotine formulation has a combined water and water-miscible solvent content of about 75 weight percent or more. More preferred that the liquid nicotine formulation has a combined water and water-miscible solvent content of about 80 weight percent or more. For example, the liquid nicotine formulation may have a combined water and water-miscible solvent content of about 85 weight percent or more.

[0101] More preferably, the liquid nicotine formulation comprises water and one or more water-miscible polyhydric alcohols.

[0102] According to a more preferred embodiment of the first aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising water, one or more water-miscible polyalcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0103] According to a more preferred embodiment of the first aspect of the present invention, there is also provided a cartridge for use in an aerosol generating system, the cartridge containing a liquid nicotine formulation comprising water, one or more water-miscible polyalcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0104] According to a more preferred embodiment of the first aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising water, one or more water-miscible polyalcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0105] According to a more preferred embodiment of the second aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising water, one or more water-miscible polyalcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0106] According to a more preferred embodiment of the second aspect of the present invention, there is also provided a cartridge for use in an aerosol generating system, the cartridge containing a liquid nicotine formulation comprising water, one or more water-miscible polyalcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0107] According to a more preferred embodiment of the second aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0108] In embodiments where the liquid nicotine formulation comprises water and one or more water-miscible polyalcohols, the liquid nicotine formulation may have a combined water and water-miscible polyalcohol content of about 50 weight percent or more, about 55 weight percent or more, about 60 weight percent or more, about 65 weight percent or more, or about 70 weight percent or more.

[0109] In embodiments in which the liquid nicotine formulation comprises water and one or more water-miscible polyhydric alcohols, it is preferred that the liquid nicotine formulation has a combined water and water-miscible polyhydric alcohol content of about 75 weight percent or more. More preferred is that the liquid nicotine formulation has a combined water and water-miscible polyhydric alcohol content of about 80 weight percent or more. For example, the liquid nicotine formulation may have a combined water and water-miscible polyhydric alcohol content of about 85 weight percent or more.

[0110] Most preferably, the liquid nicotine formulation comprises water and one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol.

[0111] According to a more preferred embodiment of the first aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0112] According to a more preferred embodiment of the first aspect of the present invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids.

[0113] According to a more preferred embodiment of the first aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0114] According to a more preferred embodiment of the second aspect of the present invention, there is provided a liquid nicotine formulation for use in an aerosol generating system, the liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0115] According to a more preferred embodiment of the second aspect of the present invention, there is also provided a cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids.

[0116] According to a more preferred embodiment of the second aspect of the present invention, there is further provided an aerosol generation system comprising a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C., and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0117] In embodiments in which the liquid nicotine formulation comprises water and one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, the liquid nicotine formulation may have a combined water, glycerin, and propylene glycol content of about 50 weight percent or more, about 55 weight percent or more, about 60 weight percent or more, about 65 weight percent or more, or about 70 weight percent or more.

[0118] In embodiments in which the liquid nicotine formulation comprises water and one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, it is preferred that the liquid nicotine formulation has a combined water, glycerin and propylene glycol content of about 75 weight percent or more. More preferred is that the liquid nicotine formulation has a combined water, glycerin and propylene glycol content of about 80 weight percent or more. For example, the liquid nicotine formulation may have a combined water, glycerin and propylene glycol content of about 85 weight percent or more.

[0119] The liquid nicotine formulation comprises one or more water-immiscible solvents, which may advantageously serve to dissolve and stabilize non-polar components of the liquid nicotine formulation.

[0120] One or more water-immiscible solvents, when used in an aerosol generation system, can reduce the hygroscopicity of the aerosol generated from the liquid nicotine formulation, which can advantageously reduce or prevent an increase in particle or droplet size of the aerosol when inhaled by a user as a result of water adsorption in the respiratory tract.

[0121] When used in an aerosol generating system, liquid nicotine formulations generate aerosols that include two-phase particles or droplets that include a water-miscible phase and a water-immiscible phase.This can advantageously reduce nicotine adsorption in the upper airway and enhance pulmonary nicotine delivery and retention.Without wishing to be bound by theory, it is believed that the improvement in pulmonary nicotine delivery and retention is due to the coating or encapsulation of the water-miscible phase by the water-immiscible phase.This is believed to reduce nicotine evaporation and adsorption in the upper airway.

[0122] It is preferred that the liquid nicotine formulation has a water-immiscible solvent content of about 1 weight percent or more. It is more preferred that the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or more. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 4 weight percent or more, about 6 weight percent or more, or about 8 weight percent or more.

[0123] The liquid nicotine formulation may have a water-immiscible solvent content of about 40 percent by weight or less.

[0124] It is preferred that the liquid nicotine formulation has a water-immiscible solvent content of about 35 weight percent or less. It is more preferred that the liquid nicotine formulation has a water-immiscible solvent content of about 30 weight percent or less. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 25 weight percent or less, about 20 weight percent or less, or about 15 weight percent or less.

[0125] The liquid nicotine formulation may have a water-immiscible solvent content of about 1 weight percent to about 40 weight percent. It is preferred that the liquid nicotine formulation has a water-immiscible solvent content of about 1 weight percent to about 35 weight percent. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 1 weight percent to about 30 weight percent, about 1 weight percent to about 25 weight percent, about 1 weight percent to about 20 weight percent, or about 1 weight percent to about 15 weight percent.

[0126] The liquid nicotine formulation may have a water-immiscible solvent content of about 2 weight percent to about 40 weight percent. More preferably, the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent to about 35 weight percent. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 2 weight percent to about 30 weight percent, about 2 weight percent to about 25 weight percent, about 2 weight percent to about 20 weight percent, or about 2 weight percent to about 15 weight percent.

[0127] The liquid nicotine formulation may have a water-immiscible solvent content of about 4 weight percent to about 40 weight percent or about 4 weight percent to about 35 weight percent. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 4 weight percent to about 30 weight percent, about 4 weight percent to about 25 weight percent, about 4 weight percent to about 20 weight percent, or about 4 weight percent to about 15 weight percent.

[0128] The liquid nicotine formulation may have a water-immiscible solvent content of about 6 weight percent to about 40 weight percent or about 6 weight percent to about 35 weight percent. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 6 weight percent to about 30 weight percent, about 6 weight percent to about 25 weight percent, about 6 weight percent to about 20 weight percent, or about 6 weight percent to about 15 weight percent.

[0129] The liquid nicotine formulation may have a water-immiscible solvent content of about 8 weight percent to about 40 weight percent or about 8 weight percent to about 35 weight percent. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 8 weight percent to about 30 weight percent, about 8 weight percent to about 25 weight percent, about 8 weight percent to about 20 weight percent, or about 8 weight percent to about 15 weight percent.

[0130] Preferably, the one or more water-immiscible solvents comprise one or more partially water-soluble solvents.

[0131] As used herein in relation to the first aspect of the invention, the term "partially water-soluble solvent" refers to a compound that is liquid at 20° C. and has a water solubility of about 20 mg / mL to about 100 mg / mL at 20° C.

[0132] As used herein in relation to the second aspect of the invention, the term "partially water soluble solvent" refers to a compound that is liquid at 20°C and has a partition coefficient (log P) at 20°C of from about 0.05 to about 0.5.

[0133] One or more of the partially water-soluble solvents may have a maximum carbon chain length of less than or equal to 12. For example, one or more of the partially water-soluble solvents may have a maximum carbon chain length of less than or equal to 10.

[0134] Suitable partially water soluble solvents include, but are not limited to, polysorbate 80, triethyl citrate, and triacetin.

[0135] It is preferred that the liquid nicotine formulation has a partial water-soluble solvent content of about 0.5 weight percent or more. It is more preferred that the liquid nicotine formulation has a partial water-soluble solvent content of about 1 weight percent or more. For example, the liquid nicotine formulation may have a partial water-soluble solvent content of about 2 weight percent or more, about 4 weight percent or more, about 6 weight percent or more, about 7 weight percent or more, or about 8 weight percent or more.

[0136] It is preferred that the liquid nicotine formulation has a partial water-soluble solvent content of about 30 weight percent or less. For example, the liquid nicotine formulation may have a partial water-soluble water-immiscible solvent content of about 25 weight percent or less, about 20 weight percent or less, or about 15 weight percent or less.

[0137] It is preferred that the liquid nicotine formulation have a partial water-soluble, water-immiscible solvent content of about 0.5 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water-soluble solvent content of about 0.5 weight percent to about 25 weight percent, about 0.5 weight percent to about 20 weight percent, or about 0.5 weight percent to about 15 weight percent.

[0138] More preferably, the liquid nicotine formulation has a partial water-soluble solvent content of about 1 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water-soluble solvent content of about 1 weight percent to about 25 weight percent, about 1 weight percent to about 20 weight percent, or about 1 weight percent to about 15 weight percent.

[0139] The liquid nicotine formulation may have a partial water soluble solvent content of about 2 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water soluble solvent content of about 2 weight percent to about 25 weight percent, about 2 weight percent to about 20 weight percent, or about 2 weight percent to about 15 weight percent.

[0140] The liquid nicotine formulation may have a partial water soluble solvent content of about 4 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water soluble solvent content of about 4 weight percent to about 25 weight percent, about 4 weight percent to about 20 weight percent, or about 4 weight percent to about 15 weight percent.

[0141] The liquid nicotine formulation may have a partial water soluble solvent content of about 6 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water soluble solvent content of about 6 weight percent to about 25 weight percent, about 6 weight percent to about 20 weight percent, or about 6 weight percent to about 15 weight percent.

[0142] The liquid nicotine formulation may have a partial water soluble solvent content of about 7 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water soluble solvent content of about 7 weight percent to about 25 weight percent, about 7 weight percent to about 20 weight percent, or about 7 weight percent to about 15 weight percent.

[0143] The liquid nicotine formulation may have a partial water soluble solvent content of about 8 weight percent to about 30 weight percent. For example, the liquid nicotine formulation may have a partial water soluble solvent content of about 8 weight percent to about 25 weight percent, about 8 weight percent to about 20 weight percent, or about 8 weight percent to about 15 weight percent.

[0144] The ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be about 0.75 or greater.

[0145] That is, the weight percent partial water soluble solvent content of the liquid nicotine formulation may be at least about 0.75 times the weight percent nicotine content of the liquid nicotine formulation.

[0146] It is preferred that the ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation is greater than or equal to about 1. For example, the ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be greater than or equal to about 1.25, greater than or equal to about 1.5, or greater than or equal to about 1.75.

[0147] The ratio of the weight percent of the partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be about 20 or less.

[0148] That is, the weight percent partial water soluble solvent content of the liquid nicotine formulation may be no more than about 20 times the weight percent nicotine content of the liquid nicotine formulation.

[0149] It is preferred that the ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation is about 18 or less. For example, the ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be about 16 or less, about 14 or less, or about 12 or less.

[0150] The ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be from about 0.75 to about 20, from about 0.75 to about 18, from about 0.75 to about 16, from about 0.75 to about 14, or from about 0.75 to about 12.

[0151] It is preferred that the ratio of the weight percent partially water-soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation is from about 1 to about 20, from about 1 to about 18, from about 1 to about 16, from about 1 to about 14, or from about 1 to about 12.

[0152] The ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be from about 1.25 to about 20, from about 1.25 to about 18, from about 1.25 to about 16, from about 1.25 to about 14, or from about 1.25 to about 12.

[0153] The ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be from about 1.5 to about 20, from about 1.5 to about 18, from about 1.5 to about 16, from about 1.5 to about 14, or from about 1.5 to about 12.

[0154] The ratio of the weight percent partial water soluble solvent content to the weight percent nicotine content of the liquid nicotine formulation may be from about 1.75 to about 20, from about 1.75 to about 18, from about 1.75 to about 16, from about 1.75 to about 14, or from about 1.75 to about 12.

[0155] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be about 0.06 or greater.

[0156] That is, the weight percent partial water-soluble solvent content of the liquid nicotine formulation may be at least about 0.06 times the weight percent water-miscible solvent content of the liquid nicotine formulation.

[0157] It is preferred that the ratio of the weight percent water-miscible solvent content to the weight percent partial water-soluble solvent content of the liquid nicotine formulation is about 0.08 or greater. For example, the ratio of the weight percent partial water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be about 0.1 or greater, about 0.12 or greater, or about 0.14 or greater.

[0158] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be about 1.2 or less.

[0159] That is, the weight percent partial water-soluble solvent content of the liquid nicotine formulation may be less than or equal to about 1.2 times the weight percent water-miscible solvent content of the liquid nicotine formulation.

[0160] It is preferred that the ratio of the weight percent water-miscible solvent content to the weight percent partial water-soluble solvent content of the liquid nicotine formulation is not greater than about 1. For example, the ratio of the weight percent partial water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be not greater than about 0.8, not greater than about 0.6, or not greater than about 0.4.

[0161] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be from about 0.06 to about 1.2, from about 0.06 to about 1, from about 0.06 to about 0.8, from about 0.06 to about 0.6, or from about 0.06 to about 0.4.

[0162] It is preferred that the ratio of the weight percent of the partially water-soluble solvent content of the liquid nicotine formulation to the weight percent of the water-miscible solvent content is from about 0.08 to about 1.2, from about 0.08 to about 1, from about 0.08 to about 0.8, from about 0.08 to about 0.6, or from about 0.08 to about 0.4.

[0163] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be from about 0.1 to about 1.2, from about 0.1 to about 1, from about 0.1 to about 0.8, from about 0.1 to about 0.6, or from about 0.1 to about 0.4.

[0164] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be from about 0.12 to about 1.2, from about 0.12 to about 1, from about 0.12 to about 0.8, from about 0.1 to about 0.6, or from about 0.12 to about 0.4.

[0165] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-miscible solvent content of the liquid nicotine formulation may be from about 0.14 to about 1.2, from about 0.14 to about 1, from about 0.14 to about 0.8, from about 0.14 to about 0.6, or from about 0.14 to about 0.4.

[0166] The ratio of the weight percent partial water soluble solvent content to the weight percent water content of the liquid nicotine formulation may be about 0.025 or greater.

[0167] That is, the weight percent partial water soluble solvent content of the liquid nicotine formulation may be at least about 0.02 times the weight percent water content of the liquid nicotine formulation.

[0168] It is preferred that the ratio of the weight percent partial water soluble solvent content of the liquid nicotine formulation to the weight percent water content of the liquid nicotine formulation is about 0.03 or greater. For example, the ratio of the weight percent partial water soluble solvent content of the liquid nicotine formulation to the weight percent water content of the liquid nicotine formulation may be about 0.05 or greater, about 0.075 or greater, or about 0.1 or greater.

[0169] The ratio of the weight percent partial water soluble solvent content to the weight percent water content of the liquid nicotine formulation may be about 5 or less.

[0170] That is, the weight percent partial water soluble solvent content of the liquid nicotine formulation may be no more than about 5 times the weight percent water content of the liquid nicotine formulation.

[0171] It is preferred that the ratio of the weight percent partial water soluble solvent content of the liquid nicotine formulation to the weight percent water content is about 1 or less. For example, the ratio of the weight percent partial water soluble solvent content of the liquid nicotine formulation to the weight percent water content of the liquid nicotine formulation may be about 0.8 or less, about 0.6 or less, or about 0.4 or less.

[0172] The ratio of the weight percent partially water-soluble solvent content of the liquid nicotine formulation to the weight percent water content may be from about 0.02 to about 1.2, from about 0.02 to about 1, from about 0.02 to about 0.8, from about 0.02 to about 0.6, or from about 0.02 to about 0.4.

[0173] It is preferred that the ratio of the weight percent of the partially water-soluble solvent content of the liquid nicotine formulation to the weight percent of the water content is about 0.03 to about 1.2, about 0.03 to about 1, about 0.03 to about 0.8, about 0.03 to about 0.6, or about 0.03 to about 0.4.

[0174] The ratio of the weight percent partially water-soluble solvent content of the liquid nicotine formulation to the weight percent water content may be from about 0.05 to about 1.2, from about 0.05 to about 1, from about 0.05 to about 0.8, from about 0.05 to about 0.6, or from about 0.05 to about 0.4.

[0175] The ratio of the weight percent partial water soluble solvent content to the weight percent water content of the liquid nicotine formulation may be from about 0.75 to about 1.2, from about 0.75 to about 1, from about 0.75 to about 0.8, from about 0.75 to about 0.6, or from about 0.75 to about 0.4.

[0176] The ratio of the weight percent partially water-soluble solvent content of the liquid nicotine formulation to the weight percent water content may be from about 0.1 to about 1.2, from about 0.1 to about 1, from about 0.1 to about 0.8, from about 0.1 to about 0.6, or from about 0.1 to about 0.4.

[0177] Preferably, the one or more water immiscible solvents comprise one or more water insoluble solvents.

[0178] As used herein in relation to the first aspect of the invention, the term "water-insoluble solvent" refers to a compound that is liquid at 20°C and has a water solubility of about 5 mg / mL or less at 20°C.

[0179] As used herein in relation to the second aspect of the invention, the term "water-insoluble solvent" refers to a compound that is liquid at 20°C and has a partition coefficient (log P) of greater than about 5 at 20°C.

[0180] The one or more water-insoluble solvents may have a maximum carbon chain length of 30 or less. For example, the one or more water-insoluble solvents may have a maximum carbon chain length of 20 or less, 18 or less, 16 or less, 14 or less, or 12 or less.

[0181] Suitable water insoluble solvents include, but are not limited to, oleic acid and MIGLYOL® (a mixture of decanoyl and octanoyl glycerides).

[0182] It is preferred that the liquid nicotine formulation has a water-insoluble solvent content of about 0.5 weight percent or more.It is more preferred that the liquid nicotine formulation has a water-insoluble solvent content of about 1 weight percent or more.For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 2 weight percent or more, about 3 weight percent or more, about 4 weight percent or more, or about 6 weight percent or more.

[0183] The liquid nicotine formulation may have a water-insoluble solvent content of about 30 percent by weight or less.

[0184] It is preferred that the liquid nicotine formulation has a water-insoluble solvent content of about 25 weight percent or less. For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 20 weight percent or less, about 15 weight percent or less, or about 10 weight percent or less.

[0185] It is preferred that the liquid nicotine formulation has a water-insoluble solvent content of about 0.5 weight percent to about 25 weight percent. For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 0.5 weight percent to about 20 weight percent, about 0.5 weight percent to about 15 weight percent, or about 0.5 weight percent to about 10 weight percent.

[0186] It is more preferred that the liquid nicotine formulation has a water-insoluble solvent content of about 1 weight percent to about 25 weight percent. For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 1 weight percent to about 20 weight percent, about 1 weight percent to about 15 weight percent, or about 1 weight percent to about 10 weight percent.

[0187] The liquid nicotine formulation may have a water-insoluble solvent content of about 2 weight percent to about 25 weight percent. For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 2 weight percent to about 20 weight percent, about 2 weight percent to about 15 weight percent, or about 2 weight percent to about 10 weight percent.

[0188] The liquid nicotine formulation may have a water-insoluble solvent content of about 3 weight percent to about 25 weight percent. For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 3 weight percent to about 20 weight percent, about 3 weight percent to about 15 weight percent, or about 3 weight percent to about 10 weight percent.

[0189] The liquid nicotine formulation may have a water-insoluble solvent content of about 4 weight percent to about 25 weight percent. For example, the liquid nicotine formulation may have a water-insoluble solvent content of about 4 weight percent to about 20 weight percent, about 4 weight percent to about 15 weight percent, or about 4 weight percent to about 10 weight percent.

[0190] More preferably, the one or more water immiscible solvents include one or more partially water soluble solvents and one or more water insoluble solvents.

[0191] The ratio of the weight percent partially water-soluble solvent content to the weight percent water-insoluble solvent content of the liquid nicotine formulation may be about 0.2 or greater.

[0192] That is, the weight percent partial water-soluble solvent content of the liquid nicotine formulation may be at least about 0.2 times the weight percent water-insoluble solvent content of the liquid nicotine formulation.

[0193] It is preferred that the ratio of the weight percent partial water-soluble solvent content of the liquid nicotine formulation to the weight percent water-insoluble solvent content of the liquid nicotine formulation is about 0.4 or greater. For example, the ratio of the weight percent partial water-soluble solvent content of the liquid nicotine formulation to the weight percent water-insoluble solvent content of the liquid nicotine formulation may be about 0.6 or greater, about 0.8 or greater, or about 1 or greater.

[0194] The ratio of the weight percent partial water soluble solvent content to the weight percent water insoluble solvent content of the liquid nicotine formulation may be about 35 or less.

[0195] That is, the weight percent partial water-soluble solvent content of the liquid nicotine formulation may be 35 times or less than the weight percent water-insoluble solvent content of the liquid nicotine formulation.

[0196] It is preferred that the ratio of the weight percent partial water soluble solvent content of the liquid nicotine formulation to the weight percent water insoluble solvent content of the liquid nicotine formulation is about 30 or less. For example, the ratio of the weight percent partial water soluble solvent content of the liquid nicotine formulation to the weight percent water insoluble solvent content of the liquid nicotine formulation may be about 25 or less, about 20 or less, or about 15 or less.

[0197] The ratio of the weight percent partially water-soluble solvent content of the liquid nicotine formulation to the weight percent water-insoluble solvent content of the liquid nicotine formulation may be from about 0.2 to about 35, from about 0.2 to about 30, from about 0.2 to about 25, from about 0.2 to about 20, or from about 0.2 to about 15.

[0198] It is preferred that the ratio of the weight percent of the partially water-soluble solvent content of the liquid nicotine formulation to the weight percent of the water-insoluble solvent content is about 0.4 to about 35, about 0.4 to about 30, about 0.4 to about 25, about 0.4 to about 20, or about 0.4 to about 15.

[0199] The ratio of the weight percent partially water-soluble solvent content of the liquid nicotine formulation to the weight percent water-insoluble solvent content of the liquid nicotine formulation may be from about 0.6 to about 35, from about 0.6 to about 30, from about 0.6 to about 25, from about 0.6 to about 20, or from about 0.6 to about 15.

[0200] The ratio of the weight percent partially water-soluble solvent content of the liquid nicotine formulation to the weight percent water-insoluble solvent content of the liquid nicotine formulation may be from about 0.8 to about 35, from about 0.8 to about 30, from about 0.8 to about 25, from about 0.8 to about 20, or from about 0.8 to about 15.

[0201] The liquid nicotine formulation comprises one or more water-soluble organic acids, which may advantageously bind to the nicotine in the liquid nicotine formulation through the formation of one or more nicotine salts.

[0202] One or more nicotine salts may advantageously be dissolved and stabilized in one or more water-miscible solvents, which may advantageously reduce nicotine adsorption in the upper respiratory tract and enhance pulmonary nicotine delivery and retention.

[0203] In embodiments in which the liquid nicotine formulation comprises water and one or more water-miscible solvents, the one or more nicotine salts may advantageously be dissolved and stabilized in the water and one or more water-miscible solvents.

[0204] It is preferred that the liquid nicotine formulation comprises one or more water soluble carboxylic acids.

[0205] Suitable water soluble carboxylic acids include, but are not limited to, acetic acid, citric acid, lactic acid, levulinic acid, malic acid, malonic acid, and pyruvic acid.

[0206] More preferably, the liquid nicotine formulation comprises lactic acid.

[0207] It is preferred that the liquid nicotine formulation have a water soluble organic acid content of about 2 weight percent or greater. More preferably, the liquid nicotine formulation has a water soluble acid content of about 3 weight percent or greater.

[0208] It is preferred that the liquid nicotine formulation have a water soluble organic acid content of about 8 weight percent or less.More preferably, the liquid nicotine formulation has a water soluble organic acid content of about 6 weight percent or less.

[0209] It is preferred that the liquid nicotine formulation has a water-soluble organic acid content of about 2 weight percent to about 8 weight percent. For example, the liquid nicotine formulation may have a water-soluble organic acid content of about 2 weight percent to about 6 weight percent.

[0210] More preferably, the liquid nicotine formulation has a water-soluble organic acid content of about 3 weight percent to about 8 weight percent. For example, the liquid nicotine formulation may have a water-soluble organic acid content of about 2 weight percent to about 6 weight percent.

[0211] The liquid nicotine formulation may be a substantially caffeinated liquid nicotine formulation.

[0212] As used herein in connection with the present invention, the term "substantially decaffeinated liquid nicotine formulation" refers to a liquid nicotine formulation having a caffeine content of less than 0.5 weight percent. For example, the liquid nicotine formulation may have a caffeine content of less than about 0.4 weight percent, less than about 0.3 weight percent, or less than about 0.2 weight percent.

[0213] The liquid nicotine formulation may be a substantially caffeine-free liquid nicotine formulation.

[0214] As used herein in connection with the present invention, the term "substantially caffeine-free liquid nicotine formulation" refers to a liquid nicotine formulation having a caffeine content of less than about 0.1 percent by weight.

[0215] The liquid nicotine formulation may be a caffeine-free liquid nicotine formulation.

[0216] As used herein in connection with the present invention, the term "caffeine-free liquid nicotine formulation" refers to a liquid nicotine formulation having zero percent caffeine content by weight.

[0217] As used herein in connection with the present invention, the term "caffeine" refers to caffeine or a caffeine salt. When referring to a caffeine salt, the amount of caffeine recited herein is the amount of the caffeine cation.

[0218] The liquid nicotine formulation may include one or more solid emulsifiers.

[0219] As used herein in connection with the present invention, the term "solid emulsifier" refers to an emulsifier that is solid at 20° C. Suitable solid emulsifiers include, but are not limited to, 1-stearoyl-rac-glycerol, Kolliphor® P 188, sodium caseinate, sodium dodecanoate, and sodium docusate.

[0220] It is preferred that the liquid nicotine formulation have a solid emulsifier content of about 8 weight percent or less. More preferred that the liquid nicotine formulation have a solid emulsifier content of about 5 weight percent or less.

[0221] The liquid nicotine formulation may include one or more flavorants. Suitable flavorants include, but are not limited to, menthol.

[0222] It is preferred that the liquid nicotine formulation have a flavorant content of about 4 weight percent or less. More preferred that the liquid nicotine formulation have a flavorant content of about 3 weight percent or less.

[0223] According to the present invention there is provided a cartridge for use in an aerosol generating system, the cartridge containing a liquid nicotine formulation according to the present invention.

[0224] The cartridge may include an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0225] A cartridge containing a liquid nicotine formulation and an atomizer configured to generate an aerosol from the liquid nicotine formulation may be referred to as a "cartridge."

[0226] The atomizer may be a thermal atomizer.

[0227] As used herein in connection with the present invention, the term "thermal atomizer" refers to an atomizer configured to heat a liquid nicotine formulation to generate an aerosol.

[0228] The cartridge may include any suitable type of thermal atomizer.

[0229] The thermal atomizer may comprise a heater and a liquid transport element configured to transport the liquid nicotine formulation to the heater.

[0230] The liquid transport element may comprise a capillary wick.The heater may comprise a heater coil.

[0231] The thermal atomizer may comprise an electric heater, for example, the thermal atomizer may comprise an electric heater comprising a resistive or inductive heating element.

[0232] The atomizer may be a non-thermal atomizer.

[0233] As used herein in connection with the present invention, the term "non-thermal atomizer" refers to an atomizer configured to generate an aerosol from a liquid nicotine formulation by means other than heating.

[0234] The cartridge may include any suitable type of non-thermal atomizer.

[0235] For example, the non-thermal atomizer may be an impingement jet atomizer, an ultrasonic atomizer, or a vibrating mesh atomizer.

[0236] According to the present invention there is further provided an aerosol generation system comprising a liquid nicotine formulation according to the present invention and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0237] The atomizer may be a thermal atomizer.

[0238] The aerosol generating system may include any suitable type of thermal atomizer.

[0239] The thermal atomizer may comprise a heater and a liquid transport element configured to transport the liquid nicotine formulation to the heater.

[0240] The liquid transport element may comprise a capillary wick.The heater may comprise a heater coil.

[0241] The thermal atomizer may comprise an electric heater, for example, the thermal atomizer may comprise an electric heater comprising a resistive or inductive heating element.

[0242] The atomizer may be a non-thermal atomizer.

[0243] The aerosol generating system may comprise any suitable type of non-thermal atomizer.

[0244] For example, the non-thermal atomizer may be an impingement jet atomizer, an ultrasonic atomizer, or a vibrating mesh atomizer.

[0245] The aerosol generation system may comprise a cartridge according to the invention containing a liquid nicotine formulation, and an aerosol generation device comprising a housing defining a device cavity configured to receive at least a portion of the cartridge.

[0246] The aerosol generation system may comprise a consumable cartridge according to the invention containing a liquid nicotine formulation, and a reusable aerosol generation device comprising a housing defining a device cavity configured to receive at least a portion of the cartridge.

[0247] The aerosol generating device may include a battery and control electronics.

[0248] The aerosol generation system may comprise a cartridge according to the invention containing a liquid nicotine formulation and an atomizer, and an aerosol generation device comprising a housing defining a device cavity configured to receive at least a portion of the cartridge.

[0249] The aerosol generation system may comprise a cartridge according to the invention containing a liquid nicotine formulation, and an aerosol generation device comprising a housing defining a device cavity configured to receive the cartridge and at least a portion of an atomizer.

[0250] For the avoidance of doubt, features described above with respect to one aspect of the invention may also be applied to other aspects of the invention. In particular, features described above with respect to a liquid nicotine formulation according to the invention may also, where appropriate, relate to a cartridge according to the invention and to an aerosol generating system according to the invention. In particular, features described above with respect to a cartridge according to the invention may also, where appropriate, relate to an aerosol generating system according to the invention and vice versa.

[0251] Embodiments of the present invention will now be described, by way of example only, with reference to the following examples.

[0252] Examples 1 to 3 Three liquid nicotine formulations according to the present invention (Examples 1, 2, and 3) were prepared having the compositions shown in Tables 2, 3, and 4. [Table 2] Table 2 [Table 3] Table 3 [Table 4] Table 4

[0253] Examples A to F Six liquid nicotine formulations according to the invention (Examples A, B, C, D, E, and F) were prepared having the compositions shown in Table 5. For comparison, two liquid nicotine formulations not according to the invention (Examples G and H) were also prepared having the compositions shown in Table 5.

[0254] The liquid nicotine formulations of Examples A to H were each loaded into a cartridge of a Solaris electronic cigarette. The nicotine retention rate of the aerosol generated when the cartridge in the Solaris electronic cigarette was used was measured according to Seeman, JI; Lipowicz, PJ; Piade, J.-J.; Poget, L.; Sanders, EB; Snyder, JP; Trowbridge, CG, On the Deposition of Volatiles and Semivolatiles from Cigarette Smoke Aerosols: Relative Rates of Transfer of Nicotine and Ammonia from Particles to the Gas Phase. Chemical Research in Toxicology Measurements were made using the denuder tube technique essentially as described in 2004,17,1020-1037, with the following modifications: the aerosol was pulled rather than pushed, a 55 mL puff was used instead of a 35 mL puff, the denuder used was a 30 m Tygon® tube, and the difference in nicotine yield was measured by comparing that collected on the Cambridge pad from the product with and without the Tygon® tube, rather than measuring that collected by the denuder and that collected by a Cambridge pad positioned after the denuder. For comparison, the nicotine retention of the smoke generated when a conventional cigarette (Example I) was burned was also measured. The results are shown in Table 5.

[0255] As shown in Table 5, aerosols generated from liquid nicotine formulations according to the invention (Examples A-F) provide greater than 40% nicotine retention. In contrast, aerosols generated from liquid formulations not according to the invention (Examples G and H) provide lower nicotine retention, less than 30%.

[0256] The nicotine retention properties of the aerosols generated from the liquid nicotine formulations according to the present invention (Examples A-F) are at least 13.5 times higher than a liquid formulation not according to the present invention (Example G) which does not contain either a water-immiscible solvent or a water-soluble organic acid having a water solubility of about 100 mg / mL or less at 20°C.

[0257] The nicotine retention characteristics of the aerosols generated from the liquid nicotine formulations according to the present invention (Examples A-F) are at least about 1.5 times higher than a liquid formulation not according to the present invention (Example H) that does not contain a water-immiscible solvent having a water solubility of about 100 mg / mL or less at 20°C.

[0258] The nicotine retention characteristics of the aerosol generated from liquid nicotine formulations according to the present invention (Examples A-F) that contain both a water-immiscible solvent having a water solubility of about 100 mg / mL or less at 20° C. and a water-soluble organic acid are similar to the nicotine retention characteristics of the smoke generated from a conventional cigarette (Example I). [Table 5]

Claims

1. 1. A liquid nicotine formulation for use in an aerosol generating system, comprising: one or more water-miscible solvents; one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20° C.; one or more water-soluble organic acids, A liquid nicotine formulation, wherein the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or greater.

2. 2. The liquid nicotine formulation of claim 1, wherein the one or more water-immiscible solvents comprise one or more partially water-soluble solvents having a water solubility of about 20 mg / mL to about 100 mg / mL at 20°C.

3. 3. The liquid nicotine formulation of claim 1 or 2, wherein the one or more water-immiscible solvents comprise one or more water-insoluble solvents having a water solubility of about 5 mg / mL or less at 20°C.

4. 1. A liquid nicotine formulation for use in an aerosol generating system, comprising: one or more water-miscible solvents; one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or greater at 20° C.; one or more water-soluble organic acids, A liquid nicotine formulation, wherein the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or greater.

5. 5. The liquid nicotine formulation of claim 4, wherein the one or more water-immiscible solvents comprise one or more partially water-soluble solvents having a partition coefficient (log P) at 20° C. of about 0.05 to about 0.

5.

6. 6. The liquid nicotine formulation of claim 4 or 5, wherein the one or more water-immiscible solvents comprise one or more water-insoluble solvents having a partition coefficient (log P) at 20° C. of greater than about 5.

7. The liquid nicotine formulation of any one of claims 1 to 6, wherein the liquid nicotine formulation comprises water.

8. 9. The liquid nicotine formulation of any one of claims 1 to 8, wherein the one or more water-miscible solvents are one or more water-miscible polyhydric alcohols.

9. 9. The liquid nicotine formulation of any one of claims 1 to 8, wherein the one or more water-miscible solvents are one or more water-miscible polyhydric alcohols selected from the group consisting of 1,3-butanediol, glycerin, propylene glycol, and triethylene glycol.

10. 10. The liquid nicotine formulation of any one of claims 1 to 9, wherein the one or more water-immiscible solvents are selected from the group consisting of oleic acid, MIGLYOL®, triacetin, and triethyl citrate.

11. 11. The liquid nicotine formulation of any one of claims 1 to 10, having a water-soluble organic acid content of about 2 weight percent or greater.

12. 12. The liquid nicotine formulation of any one of claims 1 to 11, wherein the one or more water-soluble organic acids are selected from the group consisting of acetic acid, lactic acid, levulinic acid, and pyruvic acid.

13. A cartridge for use in an aerosol generation system, the cartridge containing a liquid nicotine formulation according to any one of claims 1 to 12.

14. 14. The cartridge of claim 13, comprising an atomizer configured to generate an aerosol from the liquid nicotine formulation.

15. 1. An aerosol generation system comprising: A liquid nicotine formulation according to any one of claims 1 to 12, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

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