Nicotine liquid formulations and methods for aerosol devices

Abstract

The present invention provides a method for generating an inhalable aerosol containing nicotine for delivery to a user. [Solution] A nicotine liquid formulation comprising nicotine, an acid, and a bioacceptable liquid carrier, wherein an amount of the nicotine liquid formulation is heated using a cryoelectronic vaporizer, i.e., an e-cigarette, thereby generating an inhalable aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and at least about 90% of the nicotine in the amount is present in the aerosol.

Description

Technical Field

[0001] <Cross-reference> This application claims the benefit of U.S. Provisional Patent Application No. 61 / 912,507, filed on December 5, 2013, the entire disclosure of which is incorporated herein by reference.

[0002] Summary of the Invention In some aspects, provided herein is a method of generating an inhalable aerosol containing nicotine for delivery to a user, the method comprising using a low-temperature electron volatilization device, i.e., an electronic cigarette, comprising a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine, an acid, and a biologically acceptable liquid carrier, and the step of using the electronic cigarette comprises supplying an amount of the nicotine liquid formulation to the heater, the heater forming an aerosol by heating the amount of the nicotine liquid formulation, at least about 50% of the acid in the amount being in the aerosol, and at least about 90% of the nicotine in the amount being in the aerosol.

[0003] In some embodiments, the amount comprises about 4 μL of the nicotine liquid formulation. In some embodiments, the amount comprises about 4.5 mg of the nicotine liquid formulation. In some embodiments, the concentration of the nicotine ranges from about 0.5% (w / w) to about 20% (w / w). In some embodiments, the molar ratio of the acid to the nicotine ranges from about 0.25:1 to about 4:1. In some embodiments, the acid comprises one or more acidic functional groups, and the molar ratio of the acidic functional groups to the nicotine ranges from about 0.25:1 to about 4:1. In some embodiments, the acid and the nicotine form a nicotine salt. In some embodiments, the nicotine is stable in the nicotine salt in the inhalable aerosol. In some embodiments of the methods described herein, the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt. In some embodiments of the methods described herein, one or more particles of the inhalable aerosol are sized for delivery to the user's lungs. In some embodiments of the methods described herein, the acid is selected from the group consisting of: benzoic acid, pyruvic acid, salicylic acid, levulinic acid, succinic acid, and citric acid. In some embodiments of the methods described herein, the acid is selected from the group consisting of: benzoic acid, pyruvic acid, and salicylic acid. In some embodiments of the methods described herein, the acid is benzoic acid. In some embodiments of the methods described herein, the concentration is from about 2% (w / w) to about 6% (w / w). In some embodiments of the methods described herein, the concentration is from about 5% (w / w). In some embodiments of the methods described herein, the bioacceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin. In some embodiments of the methods described herein, the bioacceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.In some embodiments of the methods described herein, the heater heats the amount of the nicotine liquid formulation to about 150°C to about 250°C. In some embodiments of the methods described herein, the heater heats the amount of the nicotine liquid formulation to about 180°C to about 220°C. In some embodiments of the methods described herein, the heater heats the amount of the nicotine liquid formulation to about 200°C. In some embodiments of the methods described herein, the nicotine liquid formulation further comprises an additional acid selected from the group consisting of: benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. In some embodiments of the methods described herein, the additional acid forms an additional nicotine salt. In some embodiments of the methods described herein, at least about 60% to about 90% of the acid in the amount is present in the aerosol. In some embodiments of the methods described herein, at least about 70% to about 90% of the acid in the amount is present in the aerosol. In some embodiments of the methods described herein, at least about 80% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the methods described herein, more than about 90% of the acid in the given amount is present in the aerosol.

[0004] In some embodiments, provided herein is a method for producing an inhalable aerosol containing nicotine for delivery to a user, comprising the steps of using a cryogenic electron vaporizer, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of about 0.5% (w / w) to about 20% (w / w), an acid having a molar ratio to the nicotine of about 0.25:1 to about 4:1, and a bioacceptable liquid carrier, and the steps of using an e-cigarette comprise the steps of providing an amount of the nicotine liquid formulation to the heater, which heats the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0005] In some embodiments, provided herein is a method for producing an inhalable aerosol containing nicotine for delivery to a user, comprising the steps of using a cryogenic electron vaporizer, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of about 2% (w / w) to about 6% (w / w), an acid having a molar ratio to the nicotine of about 1:1 to about 4:1, and a bioacceptable liquid carrier, and the steps of using an e-cigarette comprise the steps of providing an amount of the nicotine liquid formulation to the heater, which heats the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0006] In some embodiments, provided herein is a method for producing an inhalable aerosol containing nicotine for delivery to a user, comprising the steps of using a cryogenic electron vaporizer, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of about 2% (w / w) to about 6% (w / w), an acid having a molar ratio to the nicotine of about 1:1 to about 4:1, and a bioacceptable liquid carrier, and the steps of using an e-cigarette comprise the steps of providing an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0007] In some embodiments, provided herein is a method for producing an inhalable aerosol containing nicotine for delivery to a user, comprising the steps of using a cryogenic electron vaporizer, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of about 2% (w / w) to about 6% (w / w), benzoic acid in a molar ratio of about 1:1 to the nicotine, and a bioacidible liquid carrier, and the steps of using an e-cigarette comprise the steps of providing an amount of the nicotine liquid formulation to the heater, which heats the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the benzoic acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0008] In some embodiments, provided herein are cartridges for use in a cryogenic electron vaporizer, i.e., an e-cigarette, the cartridge comprising a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment comprising a nicotine preparation comprising nicotine, an acid, and a bioacidable liquid carrier, the e-cigarette providing an amount of the nicotine liquid preparation to the heater, the heater heating the amount of the nicotine liquid preparation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0009] In some embodiments of the cartridges described herein, the amount comprises about 4 μL of a nicotine liquid formulation. In some embodiments of the cartridges described herein, the amount comprises about 4.5 mg of a nicotine liquid formulation. In some embodiments of the cartridges described herein, the concentration of the nicotine ranges from about 0.5% (w / w) to about 20% (w / w). In some embodiments of the cartridges described herein, the molar ratio of the acid to the nicotine ranges from about 0.25:1 to about 4:1. In some embodiments of the cartridges described herein, the acid comprises one or more acidic functional groups, and the molar ratio of the acidic functional groups to the nicotine ranges from about 0.25:1 to about 4:1. In some embodiments of the cartridges described herein, the acid and the nicotine form a nicotine salt. In some embodiments of the cartridges described herein, the nicotine is stable in the nicotine salt in the inhalable aerosol. In some embodiments of the cartridges described herein, the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt. In some embodiments of the cartridges described herein, one or more particles of the inhalable aerosol are sized to be delivered to the user's lungs. In some embodiments of the cartridges described herein, the acid is selected from the group consisting of: benzoic acid, pyruvic acid, salicylic acid, levulinic acid, succinic acid, and citric acid. In some embodiments of the cartridges described herein, the acid is selected from the group consisting of: benzoic acid, pyruvic acid, and salicylic acid. In some embodiments of the cartridges described herein, the acid is benzoic acid. In some embodiments of the cartridges described herein, the concentration is from about 2% (w / w) to about 6% (w / w). In some embodiments of the cartridges described herein, the concentration is about 5% (w / w).In some embodiments of the cartridges described herein, the bioacceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin. In some embodiments of the cartridges described herein, the bioacceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin. In some embodiments of the cartridges described herein, the heater heats the amount of the nicotine liquid formulation to about 150°C to about 250°C. In some embodiments of the cartridges described herein, the heater heats the amount of the nicotine liquid formulation to about 180°C to about 220°C. In some embodiments of the cartridges described herein, the heater heats the amount of the nicotine liquid formulation to about 200°C. In some embodiments of the cartridges described herein, the nicotine liquid formulation further comprises an additional acid selected from the group consisting of: benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. In some embodiments of the cartridges described herein, the additional acid forms an additional nicotine salt. In some embodiments of the cartridges described herein, at least about 60% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the cartridges described herein, at least about 70% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the cartridges described herein, at least about 80% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the cartridges described herein, more than about 90% of the acid in the given amount is present in the aerosol.

[0010] In some embodiments, provided herein are cartridges for use in cryoelectronic volatilizers, i.e., e-cigarettes, the cartridge comprising a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment comprising a nicotine liquid formulation, the nicotine liquid formulation comprising: nicotine at a concentration from about 0.5% (w / w) to about 20% (w / w); an acid having a molar ratio to nicotine from about 0.25:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises providing an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, the aerosol comprising at least about 50% of the acid in the amount and about 90% of the nicotine in the amount.

[0011] In some embodiments, provided herein are cartridges for use in cryogenic electron vaporizers, i.e., e-cigarettes, the cartridge comprising a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment comprising a nicotine liquid formulation, the nicotine liquid formulation comprising: nicotine at a concentration of about 2% (w / w) to about 6% (w / w); an acid having a molar ratio to nicotine of about 1:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises providing an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0012] In some embodiments, provided herein are cartridges for use in cryogenic electron vaporizers, i.e., e-cigarettes, the cartridge comprising a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment comprising a nicotine liquid formulation, the nicotine liquid formulation comprising: nicotine at a concentration from about 2% (w / w) to about 6% (w / w); an acid having a molar ratio to nicotine from about 1:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises providing an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0013] In some embodiments, provided herein are cartridges for use in a cryoelectronic volatilizer, i.e., an e-cigarette, the cartridge comprising a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment comprising a nicotine liquid formulation, the nicotine liquid formulation comprising: nicotine at a concentration of about 2% (w / w) to about 6% (w / w); benzoic acid in a molar ratio to nicotine of about 1:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprising providing an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the benzoic acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0014] In some embodiments, provided herein are formulations for use in a cryogenic electron vaporizer including a heater, i.e., an e-cigarette, the formulation comprising nicotine, an acid, and a biologically acceptable liquid carrier; the use of the e-cigarette comprises providing the heater with an amount of the nicotine liquid formulation, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0015] In some embodiments of the formulations described herein, the amount comprises about 4 μL of liquid nicotine formulation. In some embodiments of the formulations described herein, the amount comprises about 4.5 mg of liquid nicotine formulation. In some embodiments of the formulations described herein, the concentration of nicotine ranges from about 0.5% (w / w) to about 20% (w / w). In some embodiments of the cartridges described herein, the molar ratio of the acid to the nicotine ranges from about 0.25:1 to about 4:1. In some embodiments of the formulations described herein, the acid comprises one or more acidic functional groups, and the molar ratio of the acidic functional groups to the nicotine ranges from about 0.25:1 to about 4:1. In some embodiments of the formulations described herein, the acid and the nicotine form a nicotine salt. In some embodiments of the formulations described herein, the nicotine is stable in the nicotine salt in the inhalable aerosol. In some embodiments of the formulations described herein, the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt. In some embodiments of the formulations described herein, one or more particles of the inhalable aerosol are sized for delivery to the user's lungs. In some embodiments of the formulations described herein, the acid is selected from the group consisting of: benzoic acid, pyruvic acid, salicylic acid, levulinic acid, succinic acid, and citric acid. In some embodiments of the formulations described herein, the acid is selected from the group consisting of: benzoic acid, pyruvic acid, and salicylic acid. In some embodiments of the formulations described herein, the acid is benzoic acid. In some embodiments of the formulations described herein, the concentration is from about 2% (w / w) to about 6% (w / w). In some embodiments of the formulations described herein, the concentration is about 5% (w / w).In some embodiments of the formulations described herein, the bioacceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin. In some embodiments of the formulations described herein, the bioacceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin. In some embodiments of the formulations described herein, the heater heats the amount of the nicotine liquid formulation to about 150°C to about 250°C. In some embodiments of the formulations described herein, the heater heats the amount of the nicotine liquid formulation to about 180°C to about 220°C. In some embodiments of the cartridges described herein, the heater heats the amount of the nicotine liquid formulation to about 200°C. In some embodiments of the formulations described herein, the nicotine liquid formulation further comprises an additional acid selected from the group consisting of: benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. In some embodiments of the formulations described herein, the additional acid forms an additional nicotine salt. In some embodiments of the formulations described herein, at least about 60% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the formulations described herein, at least about 70% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the formulations described herein, at least about 80% to about 90% of the acid in the given amount is present in the aerosol. In some embodiments of the formulations described herein, more than about 90% of the acid in the given amount is present in the aerosol.

[0016] In some embodiments, provided herein are formulations for use in cryogenic electron vaporizers including a heater, i.e., e-cigarettes, the formulation comprising nicotine in a concentration from about 0.5% (w / w) to about 20% (w / w); an acid having a molar ratio of acid to nicotine from about 0.25:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises supplying an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0017] In some embodiments, provided herein are formulations for use in a cryogenic electron vaporizer including a heater, i.e., an e-cigarette, the formulation comprising nicotine in a concentration of about 2% (w / w) to about 6% (w / w); an acid having a molar ratio of acid to nicotine of about 1:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises supplying an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0018] In some embodiments, provided herein are formulations for use in a cryogenic electron vaporizer including a heater, i.e., an e-cigarette, the formulation comprising nicotine in a concentration of about 2% (w / w) to about 6% (w / w); an acid having a molar ratio of acid to nicotine of about 1:1 to about 4:1; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises supplying an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0019] In some embodiments, provided herein are formulations for use in a cryogenic electron vaporizer including a heater, i.e., an e-cigarette, the formulation comprising nicotine in a concentration of about 2% (w / w) to about 6% (w / w); benzoic acid in a molar ratio of about 1:1 to nicotine; and a biologically acceptable liquid carrier; the use of the e-cigarette comprises supplying an amount of the nicotine liquid formulation to the heater, the heater heating the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the benzoic acid in the amount is present in the aerosol, and about 90% of the nicotine in the amount is present in the aerosol.

[0020] <Integration by reference> All publications, patents, and patent applications shown herein are incorporated by reference in such a way that they are specifically and individually shown as if each publication, patent, and patent application were incorporated by reference. [Brief explanation of the drawing]

[0021] A better understanding of the features and advantages of the present invention can be obtained by referring to the following detailed description and accompanying drawings that illustrate exemplary embodiments in which the principles of the present invention are used. [Figure 1] Figure 1 shows an unrestricted example of heart rate data results measured for the first 6 minutes after inhalation. The Y-axis represents heart rate (bpm), and the X-axis represents the test time (-60 to 180 seconds). [Figure 2] Figure 2 shows the results of heart rate data measured for the first 10 minutes after inhalation. The Y-axis represents heart rate (bpm), and the X-axis represents the test time (0-10 minutes). [Figure 3] Figure 3 shows an unrestricted example of calculated vapor pressures for various acids relative to nicotine; [Figure 4] Figure 4 shows an unlimited example of a cryoelectronic volatilizer (i.e., e-cigarette) having a fluid storage compartment containing a nicotine liquid formulation according to embodiments herein; and, [Figure 5]Figure 5 shows a non-limiting example of a low-temperature electronic vaporization device (i.e., an e-cigarette) having a fluid storage compartment, a heater, and a cartridge containing the nicotine liquid formulation of the embodiments herein; [Figure 6] Figure 6 depicts a non-limiting example of the pharmacokinetic profiles of four test substances in plasma research. [Figure 7] Figure 7 depicts a non-limiting example of the Cmax of four test substances in plasma research. [Figure 8] Figure 8 depicts a non-limiting example of the Tmax of four test substances in plasma research. [Figure 9] Figure 9 depicts a non-limiting example of the correlation between the molar ratio of benzoic acid to nicotine and the percentage of nicotine captured from at least a portion of the aerosol generated from a low-temperature electronic vaporization device, i.e., an e-cigarette, and the nicotine liquid formulation. [Figure 10] Figure 10 depicts a non-limiting example of the percentage of nicotine captured from at least a portion of the aerosol generated from a low-temperature electronic vaporization device, i.e., an e-cigarette, and the nicotine liquid formulation. [Figure 11] Figure 11 depicts a non-limiting correlation between the molar ratio of acidic functional groups to nicotine and the percentage of nicotine captured from at least a portion of the aerosol generated from a low-temperature electronic vaporization device, i.e., an e-cigarette, and the nicotine liquid formulation.

Mode for Carrying Out the Invention

[0022] Nicotine is a chemical stimulant that increases heart rate and blood pressure when administered to an individual or animal. Nicotine transfer to an individual is associated with a physically and / or emotionally satisfied feeling. Conflicting reports have been published regarding the transfer efficiency of free base nicotine compared to mono- or di-protonated nicotine salts. Studies on the transfer efficiency of free base nicotine and nicotine salts have been complex and yielded unpredictable results. Furthermore, such transfer efficiency studies have been conducted under extremely high-temperature conditions (comparable to smoking); therefore, they provide insufficient guidance on the transfer efficiency of free base nicotine and nicotine salts under low-temperature volatilization conditions (e.g., low-temperature volatilization devices, i.e., the conditions of e-cigarettes). Some reports hypothesize that free base nicotine provides greater satisfaction to the user than any corresponding nicotine salt.

[0023] In this specification, it has been unexpectedly discovered that certain liquid nicotine formulations provide superior satisfaction to individuals compared with free base nicotine, and more comparable satisfaction to individuals who smoke conventional tobacco. The satiating effect is consistent with the efficient transport of nicotine to the lungs, as demonstrated by, for example, but not limited to, the rapid increase in nicotine absorption in the alveoli and plasma of individuals in Examples 8, 13, and 14. It has also been unexpectedly discovered in this specification that certain liquid nicotine formulations provide greater satisfaction than other liquid nicotine formulations. Such effects are demonstrated at the plasma level of the liquid nicotine formulations of the examples herein, for example, in Examples 3 and 8. These results demonstrate that the rate of nicotine uptake into the blood is higher for liquid nicotine formulations, such as nicotine salt formulations, than for free base nicotine formulations. Furthermore, studies described herein demonstrate that the transport efficiency of liquid nicotine formulations, such as nicotine salts, depends on the acid used in the formulation. : Certain acids used in nicotine liquid formulations result in better transfer from the liquid formulation to vapor and / or aerosol, but are not limited to, as demonstrated in at least Example 13. Therefore, described herein are nicotine liquid formulations, such as nicotine salt liquid formulations, for use in cryogenic devices, i.e., e-cigarettes, etc., which provide a generally satisfactory effect consistent with the efficient transfer of nicotine to the lungs of an individual and a rapid increase in nicotine absorption in the plasma. Accordingly, provided herein are liquid formulations, systems, cartomizers, kits, and methods comprising one or more nicotine salts, used for inhaling an aerosol produced from a nicotine salt liquid formulation in a cryogenic device, i.e., an e-cigarette, etc., as described herein or as obvious to those skilled in the art who have read the matters disclosed herein.

[0024] In line with these satisfying effects, we have unexpectedly discovered in this specification a difference between Cmax (maximum concentration) and Tmax (time at which maximum concentration is measured) when measuring plasma nicotine levels of free base nicotine liquid formulations inhaled using a cryogenic volatilizer, i.e., an e-cigarette, compared with Cmax (maximum concentration) and Tmax (time at which maximum concentration is measured) (similarly measuring plasma nicotine levels) of conventional tobacco. In line with these satisfying effects, we have unexpectedly discovered in this specification a difference between Cmax and Tmax (similarly measuring plasma nicotine levels) when measuring plasma nicotine levels of free base nicotine liquid formulations inhaled using a cryogenic volatilizer, i.e., an e-cigarette, compared with Cmax and Tmax (similarly measuring plasma nicotine levels) of nicotine liquid formulations such as nicotine salt liquid formulations inhaled using a cryogenic volatilizer, i.e., an e-cigarette. Furthermore, we have unexpectedly discovered a difference between the nicotine inhalation rate in the plasma of users who inhaled free base nicotine liquid formulations using a cryogenic volatilizer, i.e., an e-cigarette, compared with the nicotine inhalation rate in the plasma of users who inhaled conventional tobacco smoke. Furthermore, an unexpected difference was discovered between the nicotine inhalation rate in the plasma of users who inhaled liquid nicotine preparations, such as nicotine salt preparations, using a low-temperature vaporizer, i.e., an e-cigarette, and the nicotine inhalation rate in the plasma of users who inhaled liquid nicotine preparations, such as free base nicotine preparations, using a low-temperature vaporizer, i.e., an e-cigarette.

[0025] In some embodiments, the inhalation of vapor and / or aerosol produced using a free base nicotine composition in a cryogenic volatilizer, i.e., an e-cigarette, is not necessarily comparable at plasma levels (Cmax and Tmax) to the delivery of nicotine to the blood when conventional tobacco is inhaled. In some embodiments, the inhalation of vapor and / or aerosol produced using a free base nicotine composition in a cryogenic volatilizer, i.e., an e-cigarette, is not necessarily comparable at plasma levels (Cmax and Tmax) to the inhalation of nicotine-containing vapor and / or aerosol produced from a nicotine liquid formulation, such as a nicotine salt liquid formulation. Furthermore, the inhalation of vapor and / or aerosol produced using a free base nicotine composition in a cryogenic volatilizer, i.e., an e-cigarette, is not necessarily comparable at plasma levels to the delivery of nicotine to the blood when conventional tobacco is inhaled, when measuring the rate of nicotine inhalation into the blood during the first 0-8 minutes. Furthermore, inhalation of vapor and / or aerosol produced using a free base nicotine composition in a low-temperature vaporizer, i.e., an e-cigarette, is not necessarily comparable to inhalation of nicotine-containing vapor and / or aerosol produced from a nicotine liquid preparation, such as a nicotine salt liquid preparation, when measuring the rate of nicotine inhalation into the blood during the first 0-8 minutes, at the plasma level.

[0026] When free base nicotine is used as a nicotine source in cryogenic devices, i.e., e-cigarettes, the transfer efficiency of nicotine liquid formulations delivers more nicotine from the liquid formulation to the vapor and / or aerosol, consistent with the difference observed at plasma levels compared to nicotine liquid formulations such as nicotine salt liquid formulations. As demonstrated, Examples 13, not limited to those mentioned above, in which free base nicotine is used as a nicotine source in cryogenic devices, i.e., e-cigarettes, result in less nicotine present in the aerosol compared to when nicotine liquid formulations such as nicotine salt liquid formulations are used as a nicotine source in cryogenic devices, i.e., e-cigarettes. Furthermore, this is consistent with the difference observed at plasma nicotine levels when free base nicotine is used as a nicotine source in cryogenic devices, i.e., e-cigarettes, compared to when nicotine liquid formulations such as nicotine salt liquid formulations are used, resulting in higher transfer efficiency from liquid to vapor and / or aerosol of nicotine liquid formulations leading to higher efficiency of nicotine uptake into the bloodstream. One explanation for these observations is that nicotine-containing aerosols, such as aerosol droplets, are readily delivered to the user's lungs and / or alveoli within them, and as a result, efficiently taken up by the user's bloodstream. Furthermore, the aerosols are delivered as particles sized to reach the user's lungs, for example, the alveoli of the user's lungs, via oral or nasal passages.

[0027] Compared to vaporized nicotine, aerosolized nicotine is more suitable for reaching the user's lungs and being absorbed into the alveoli. One reason why aerosolized nicotine has a greater chance of being absorbed into the lungs compared to vaporized nicotine is that vaporized nicotine has a greater chance of being absorbed in the user's oral and upper respiratory tract tissues. Furthermore, nicotine absorbed in the mouth and upper respiratory tract is absorbed less efficiently than nicotine absorbed in the lung tissue, resulting in a less satisfactory effect for the user. As shown in at least Examples 8 and 13 (not limited to), when using a cryoelectronic vaporizer, i.e., an e-cigarette, to deliver nicotine to the user, there is a direct correlation between the time to the maximum concentration of nicotine in the blood (Tmax) and the amount of aerosolized nicotine delivered to the aerosol. For example, the use of free base nicotine liquid formulations results in a significant reduction in the amount of aerosolized nicotine compared to nicotine benzoate (1:1 molar ratio of nicotine:benzoic acid) and nicotine malate (1:2 molar ratio of nicotine:malic acid). Furthermore, as shown in Example 8 (but not limited to), the Tmax of free bases is longer compared to nicotine benzoate and nicotine malate, as a result of less aerosolized nicotine and therefore less rapid absorption into the user's lungs.

[0028] Compared to acids that do not decompose at room temperature and / or the operating temperature of the device, acids that decompose at room temperature and / or the operating temperature of the device require a higher molar ratio of acid to nicotine to transfer the same molar amount of acid from liquid to aerosol. Therefore, in some embodiments, compared to acids that do not decompose at room temperature and / or the operating temperature of the device, acids that decompose at room temperature and / or the operating temperature of the device require twice the molar amount to produce an aerosol containing the same molar amount of nicotine, and in some embodiments, a non-gas phase (e.g., droplets) of the aerosol. The correlation between the molar ratio of benzoic acid to nicotine and the proportion of captured acid, not limited but as shown in Example 13, demonstrates that more acid is in the aerosol, and in some embodiments, in the non-gas phase of the aerosol, thereby more nicotine is present in the aerosol, and in some embodiments, in the non-gas phase of the aerosol. Furthermore, malic acid is known to decompose at approximately 150°C, which is below the operating temperature of cryoelectronic devices (i.e., e-cigarettes). Furthermore, when malic acid is used in a nicotine liquid formulation, as shown in Example 13 (but not limited to), less than 50% of the malic acid in the liquid formulation is recovered. This is significantly different from the 90% of benzoic acid recovered when benzoic acid is used in a nicotine liquid formulation. The lower recovery percentage of malic acid is probably due to the decomposition of malic acid. Therefore, as shown in Example 13, approximately twice the amount of malic acid compared to benzoic acid is required to produce an aerosol containing the same molar amount of acid in the aerosol, and in some embodiments, the non-gas phase of the aerosol. Thus, in the case of malic acid, twice the amount of nicotine is required to produce an aerosol containing the same amount of nicotine in the aerosol, and in some embodiments, the non-gas phase of the aerosol. In addition, decomposition products of malic acid are probably present in the aerosol, and when the device and malic nicotine liquid formulation are used, this may result in an unpleasant experience for the user. In some embodiments, the unpleasant experience includes flavor, neurological reactions, and / or irritation of one or more of the oral cavity, upper respiratory tract, and / or lungs.

[0029] The presence of acid in the aerosol stabilizes and / or delivers nicotine to the user's lungs. In some embodiments, the formulation contains the acidic functional group in a 1:1 ratio of moles of nicotine to moles of nicotine so that nicotine is stable in the aerosol produced by a cryo-electron vaporizer, i.e., an e-cigarette. In some embodiments, the formulation contains the carboxylic acid functional group hydrogen in a 1:1 ratio of moles of nicotine to moles of nicotine so that nicotine is stable in the aerosol produced by a cryo-electron vaporizer, i.e., an e-cigarette. As shown in Example 14, nicotine is aerosolized in a 1:1 ratio of moles of benzoic acid to moles of nicotine, and since benzoic acid contains one carboxylic acid functional group, nicotine is aerosolized in a 1:1 ratio of moles of carboxylic acid functional group to moles of nicotine. Furthermore, as shown in Example 14, nicotine is aerosolized in a ratio of 0.5:1 moles of succinic acid to moles of nicotine, and since succinic acid contains two carboxylic acid functional groups, nicotine is aerosolized in a ratio of 1:1 moles of carboxylic acid functional groups to moles of nicotine. As shown in Example 14, each nicotine molecule is associated with one carboxylic acid functional group and is presumably protonated by the acid. Furthermore, this demonstrates that nicotine is presumably delivered to the user's lungs in a protonated form in the aerosol.

[0030] Several reasons for not using acids in nicotine liquid formulations are listed below. Other reasons for using specific acids in nicotine liquid formulations are unrelated to the rate of nicotine absorption. In some embodiments, acids that corrode or are unsuitable for electron vaporizer materials are not used in nicotine liquid formulations. As an example without limitation, sulfuric acid corrodes and / or reacts with the components of the device, making it unsuitable for inclusion in nicotine liquid formulations. In some embodiments, acids that are toxic to the user of the electron vaporizer are not useful in nicotine formulations because they are unsuitable for human digestion, food ingestion, or inhalation. As an example without limitation, sulfuric acid is one such acid, and depending on the embodiment of the composition, it is unsuitable for users of cryogenic electron vaporizers, i.e., e-cigarettes. In some embodiments, acids in nicotine liquid formulations that have a bitter or otherwise unpleasant taste to the user are not useful in nicotine liquid formulations. Examples without limitation of such acids are high concentrations of acetic acid or citric acid. In some embodiments, acids that oxidize at room temperature and / or the operating temperature of the device are not included in nicotine liquid formulations. Such acids, in non-limiting examples, include sorbic acid and malic acid, which are unstable at room temperature and / or the operating temperature of the apparatus. Decomposition of an acid at room temperature or the operating temperature may indicate that the acid is unsuitable for use in the formulation of the embodiment. In non-limiting examples, citric acid decomposes at 175°C and malic acid decomposes at 140°C, and since the apparatus operates at 200°C, these acids are unsuitable. In some embodiments, acids having low solubility for the components of the composition are unsuitable for use in certain embodiments of the composition herein. In non-limiting examples, nicotine tartrate, comprising nicotine and tartaric acid in a 1:2 molar ratio composition, does not produce a solution with concentrations of 0.5% (w / w) or more of nicotine and 0.9% (w / w) or more of tartaric acid in propylene glycol (PG) or vegetable glycerin (VG), or any mixture of PG and VG, at ambient conditions. As used herein, weight percent (w / w) refers to the weight of the individual components relative to the total weight of the formulation.

[0031] In some embodiments, nicotine liquid formulations (e.g., nicotine salt liquid formulations) using acids having a vapor pressure between 20–300 mmHg@200°C, or >20 mmHg@200°C, or 20 mmHg to 300 mmHg@200°C, or 20–200 mmHg@200°C, or 20–300 mmHg@200°C, provide satisfaction comparable to or closer to conventional tobacco (compared to other nicotine salt formulations or nicotine free base formulations). Examples that are not limited include salicylic acid, sorbic acid, benzoic acid, lauric acid, and levulinic acid, which satisfy one or more of the aforementioned criteria. In some embodiments, nicotine liquid formulations, such as nicotine salt liquid formulations, prepared using acids with a difference of at least 50°C between their boiling and melting points, where the boiling point exceeds 160°C and the melting point is below 160°C, provide satisfaction comparable to or closer to conventional tobacco (compared to other nicotine salt formulations or nicotine free base formulations). Examples of acids that satisfy the above criteria include salicylic acid, sorbic acid, benzoic acid, pyruvic acid, lauric acid, and levulinic acid. In some embodiments, nicotine liquid formulations, such as nicotine salt liquid formulations, prepared using acids with a difference of at least 50°C between their boiling and melting points, where the boiling point is up to 40°C lower than the operating temperature and the melting point is at least 40°C lower than the operating temperature, provide satisfaction comparable to or closer to conventional tobacco (compared to other nicotine salt formulations or nicotine free base formulations). In some embodiments, the operating temperature may be 100°C to 300°C, or about 200°C, about 150°C to about 250°C, 180°C to 220°C, about 180°C to about 220°C, 185°C to 215°C, about 185°C to about 215°C, 190°C to 210°C, about 190°C to about 210°C, 195°C to 205°C, or about 195°C to about 205°C. Examples of acids that satisfy the aforementioned criteria include salicylic acid, sorbic acid, benzoic acid, pyruvic acid, lauric acid, and levulinic acid. In some embodiments, combinations of these criteria relating to the preference of a particular nicotine salt formulation are incorporated herein.

[0032] As used herein and in the claims, the singular forms "a," "an," and "the" include plural nouns unless otherwise explicitly stated.

[0033] As used herein and in the claims, the term “vapor” refers to the gaseous or gaseous phase of a material. As used herein and in the claims, the term “aerosol” refers to a colloidal suspension of particles (e.g., droplets) dispersed in air or gas.

[0034] As used herein, the term “organic acid” refers to an organic compound possessing acidic properties (e.g., according to the definitions of Bronsted-Lowry or Lewis). Common organic acids are carboxylic acids associated with a carboxyl group-COOH, which is the source of their acidity. Dicarboxylic acids have two carboxylic acid groups. The relative acidity of an organic compound is measured by its pKa value, and those skilled in the art know how to determine the acidity of an organic acid based on its given pKa value. As used herein, the term “keto acid” refers to an organic compound containing a carboxylic acid group and a ketone group. Common types of keto acids include alpha-keto acids (or 2-oxo acids), such as pyruvate or oxaloacetate, which have a keto group adjacent to the carboxylic acid; beta-keto acids (or 3-oxo acids), such as acetoacetate, which have a ketone group on the second carbon from the carboxylic acid; and gamma-keto acids (or 4-oxo acids), such as levulinic acid, which have a ketone group on the third carbon from the carboxylic acid.

[0035] As used herein, the terms “electronic cigarette” or “cryogenic vaporizer” refer to an electronic inhaler that vaporizes a liquid solution into an aerosol mist, mimicking the act of smoking a cigarette. The liquid solution includes formulations containing nicotine. There are many cryogenic vaporizers, i.e., e-cigarettes, that do not resemble conventional cigarettes at all. Users can choose the amount of nicotine contained by inhalation. Generally, a cryogenic vaporizer (i.e., an e-cigarette) includes three essential components: a plastic cartridge used as a mouthpiece and another plastic cartridge that serves as a reservoir for the liquid, an “atomizer” that vaporizes the liquid, and a battery. In other embodiments, a cryogenic vaporizer (i.e., an e-cigarette) includes a combined atomizer and reservoir called a “cartomizer,” which may be disposable or not, a mouthpiece which may or may not be integrated into the cartomizer, and a battery.

[0036] Unless otherwise defined, the term “about” as used herein and in the claims refers to variations of 1%, 2%, 3%, 4%, 5%, 10%, 15%, or 25%, depending on the embodiment.

[0037] Suitable carriers (e.g., liquid solvents) for nicotine salts described herein include a medium in which the nicotine salt is soluble under ambient conditions so as not to form a solid precipitate. Examples are not limited to, but include glycerin, propylene glycol, trimethylene glycol, water, ethanol and other similar substances, and combinations thereof. In some embodiments, the liquid carrier contains about 0% to about 100% propylene glycol and about 100% to about 0% vegetable glycerin. In some embodiments, the liquid carrier contains about 10% to about 70% propylene glycol and about 90% to about 30% vegetable glycerin. In some embodiments, the liquid carrier contains about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin. In some embodiments, the liquid carrier contains up to about 30% propylene glycol and up to about 70% vegetable glycerin.

[0038] The formulations described herein differ in nicotine concentration. Some formulations have a low nicotine concentration. Some formulations have a moderate nicotine concentration. Some formulations have a nicotine concentration in the nicotine liquid formulation ranging from about 1% (w / w) to about 25% (w / w). Some formulations have a nicotine concentration in the nicotine liquid formulation ranging from about 1% (w / w) to about 20% (w / w). Some formulations have a nicotine concentration in the nicotine liquid formulation ranging from about 1% (w / w) to about 18% (w / w). In some embodiments, the nicotine concentration in the nicotine liquid formulation ranges from about 1% (w / w) to about 15% (w / w). Some formulations have a nicotine concentration in the nicotine liquid formulation ranging from about 4% (w / w) to about 12% (w / w). In some formulations, the nicotine concentration in the liquid nicotine formulation ranges from approximately 2% (w / w) to approximately 6% (w / w). In some formulations, the nicotine concentration in the liquid nicotine formulation is approximately 5% (w / w). In some formulations, the nicotine concentration in the liquid nicotine formulation is approximately 4% (w / w). In some formulations, the nicotine concentration in the liquid nicotine formulation is approximately 3% (w / w). In some formulations, the nicotine concentration in the liquid nicotine formulation is approximately 2% (w / w). In some embodiments, the nicotine concentration in the liquid nicotine formulation is approximately 1% (w / w). In some formulations, the nicotine concentration in the liquid nicotine formulation ranges from approximately 1% (w / w) to approximately 25% (w / w).

[0039] The formulations described herein differ in nicotine salt concentration. In some formulations, the concentration of nicotine salt in the nicotine liquid formulation is dilute. In some formulations, the nicotine concentration in the formulation is not so dilute. In some formulations, the concentration of nicotine salt in the nicotine liquid formulation ranges from about 1% (w / w) to about 25% (w / w). In some formulations, the concentration of nicotine salt in the nicotine liquid formulation ranges from about 1% (w / w) to about 20% (w / w). In some formulations, the concentration of nicotine salt in the nicotine liquid formulation ranges from about 1% (w / w) to about 18% (w / w). In some embodiments, the concentration of nicotine salt in the nicotine liquid formulation ranges from about 1% (w / w) to about 15% (w / w). In some formulations, the concentration of nicotine salt in the nicotine liquid formulation ranges from about 4% (w / w) to about 12% (w / w). In some formulations, the concentration of nicotine salt in the liquid nicotine formulation ranges from approximately 2% (w / w) to approximately 6% (w / w). In some formulations, the concentration of nicotine salt in the liquid nicotine formulation is approximately 5% (w / w). In some formulations, the concentration of nicotine salt in the liquid nicotine formulation is approximately 4% (w / w). In some formulations, the concentration of nicotine salt in the liquid nicotine formulation is approximately 3% (w / w). In some formulations, the concentration of nicotine salt in the liquid nicotine formulation is approximately 2% (w / w).

[0040] In some embodiments, the concentration of nicotine salt in the nicotine liquid formulation is approximately 1% (w / w). In some formulations, a less dilute concentration of one nicotine salt is used in combination with a dilute concentration of a second nicotine salt. In some formulations, the nicotine concentration in the first nicotine liquid formulation ranges from approximately 1% to approximately 20% and is combined with a second nicotine liquid formulation having a nicotine concentration ranging from approximately 1% to approximately 20%, or any range or concentration. In some formulations, the nicotine salt concentration in the first nicotine liquid formulation ranges from approximately 1% to approximately 20%, and is combined with a second nicotine liquid formulation having a nicotine concentration ranging from approximately 1% to approximately 20%, or any range or concentration. In some formulations, the nicotine salt concentration in the first nicotine liquid formulation ranges from approximately 1% to approximately 20%, and is combined with a second nicotine liquid formulation having a nicotine salt concentration ranging from approximately 1% to approximately 20%, or any range or concentration. The term "approximately" as used with respect to the concentration of nicotine in liquid nicotine formulations means, depending on the embodiment, 0.05% (i.e., if the concentration is approximately 2%, the range is 1.95%–2.05%), 0.1% (i.e., if the concentration is approximately 2%, the range is 1.9%–2.1%), 0.25% (i.e., if the concentration is approximately 2%, the range is 1.75%–2.25%), 0.5% (i.e., if the concentration is approximately 2%, the range is 1.5%–2.5%), or 1% (i.e., if the concentration is approximately 4%, the range is 3%–5%).

[0041] In some embodiments, the formulation comprises an organic acid and / or an inorganic acid. In some embodiments, the suitable organic acid comprises a carboxylic acid. Among some embodiments, the organic carboxylic acids disclosed herein include monocarboxylic acids, dicarboxylic acids (organic acids containing two carboxylic acid groups), and carboxylic acids containing aromatic groups such as benzoic acid and hydroxycarboxylic acid, heterocyclic carboxylic acids, terpenoid acids, sugar acids such as pectic acid, amino acids, alicyclic acids, ketocarboxylic acids, etc. In some embodiments, suitable acids include formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, citric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, phenylacetic acid, benzoic acid, pyruvic acid, levulinic acid, tartaric acid, lactic acid, malonic acid, succinic acid, fumaric acid, gluconic acid, sugar acids, salicylic acid, sorbic acid, malonic acid, malic acid, or a combination thereof. In some embodiments, the suitable acid includes one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. In some embodiments, the suitable acid includes one or more of benzoic acid, pyruvic acid, and salicylic acid. In some embodiments, the suitable acid includes benzoic acid.

[0042] Nicotine salts are formed by the addition of a suitable acid, including organic or inorganic acids. In some embodiments, the suitable organic acid includes carboxylic acids. In some embodiments, the organic carboxylic acids disclosed herein include monocarboxylic acids, dicarboxylic acids (organic acids containing two carboxylic acid groups), and carboxylic acids containing aromatic groups such as benzoic acid and hydroxycarboxylic acids, heterocyclic carboxylic acids, terpenoid acids, sugar acids such as pectic acid, amino acids, alicyclic acids, ketocarboxylic acids, etc. In some embodiments, the organic acid used herein is a monocarboxylic acid. Nicotine salts are formed by the addition of a suitable acid to nicotine. In some embodiments, suitable acids include formic acid and acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, citric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, phenylacetic acid, benzoic acid, pyruvic acid, levulinic acid, tartaric acid, lactic acid, malonic acid, succinic acid, fumaric acid, gluconic acid, sugar acid, salicylic acid, sorbic acid, masonic acid, malic acid, or a combination thereof. In some embodiments, suitable acids include one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. In some embodiments, suitable acids include one or more of benzoic acid, pyruvic acid, and salicylic acid. In some embodiments, suitable acids include benzoic acid.

[0043] In some embodiments, the formulations include various stoichiometric ratios and / or molar ratios of the acid to nicotine, the acidic functional group to nicotine, and the acidic functional group hydrogen to nicotine. In some embodiments, the (nicotine:acid) stoichiometric ratios of nicotine to acid are 1:1, 1:2, 1:3, 1:4, 2:3, 2:5, 2:7, 3:4, 3:5, 3:7, 3:8, 3:10, 3:11, 4:5, 4:7, 4:9, 4:10, 4:11, 4:13, 4:14, 4:15, 5:6, 5:7, 5:8, 5:9, 5:11, 5:12, 5:13, 5:14, 5:15, 5:16, 5:17, 5:18, or 5:19. In some formulations provided herein, the stoichiometric ratio of nicotine to acid is 1:1, 1:2, 1:3, or 1:4. In some embodiments, the molar ratio of acid to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. In some embodiments, the molar ratio of acidic functional groups to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. In some embodiments, the molar ratio of acidic functional group hydrogen to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1.In some embodiments, the molar ratio of acid to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. In some embodiments, the molar ratio of acidic functional groups to nicotine in the aerosol is about 0.25:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1.2:1, about 1.4:1, about 1.6:1, about 1.8:1, about 2:1, about 2.2:1, about 2.4:1, about 2.6:1, about 2.8:1, about 3:1, about 3.2:1, about 3.4:1, about 3.6:1, about 3.8:1, or about 4:1. In some embodiments, the molar ratio of acidic functional group hydrogen to nicotine in the aerosol is about 0.25:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1.2:1, about 1.4:1, about 1.6:1, about 1.8:1, about 2:1, about 2.2:1, about 2.4:1, about 2.6:1, about 2.8:1, about 3:1, about 3.2:1, about 3.4:1, about 3.6:1, about 3.8:1, or about 4:1.

[0044] Nicotine is an alkaloid molecule containing two basic nitrogen atoms. It can exist in different protonation states. For example, if no protonation is present, nicotine is considered a "free base." If one nitrogen atom is protonated, nicotine becomes "monoprotonated."

[0045] In some embodiments, nicotine liquid formulations are formed by adding a suitable acid to nicotine, stirring the suitable mixture at ambient temperature or a higher temperature, and then diluting the suitable mixture with a carrier mixture such as a mixture of propylene glycol and glycerin. In some embodiments, the suitable acid is completely dissolved by the nicotine prior to dilution. The suitable acid may not be completely dissolved by the nicotine prior to dilution. The addition of the suitable acid to the nicotine to form the suitable mixture may cause an exothermic reaction. The addition of the suitable acid to the nicotine to form the suitable mixture may be carried out at 55°C. The addition of the suitable acid to the nicotine to form the suitable mixture may be carried out at 90°C. The suitable mixture may be cooled to ambient temperature prior to dilution. Dilution may be carried out at a higher temperature.

[0046] In some embodiments, the nicotine liquid formulation is prepared by combining nicotine with a suitable acid in a carrier mixture such as a mixture of propylene glycol and glycerin. The mixture of nicotine and the first carrier mixture is combined with a mixture of a suitable acid in a second carrier mixture. In some embodiments, the first and second carrier mixtures are identical in composition. In some embodiments, the first and second carrier mixtures are not identical in composition. In some embodiments, heating of the nicotine / acid / carrier mixture is required to promote complete dissolution. In some embodiments, stirring of the nicotine / acid / carrier mixture is sufficient to promote complete dissolution.

[0047] In some embodiments, a liquid nicotine formulation is prepared and added to a propylene glycol (PG) / vegetable glycerin (VG) solution in a weight ratio of 3:7 and thoroughly mixed. Although it is stated herein that 10 g of each formulation is produced, all the procedures described below are measurable. Other forms of formulations may be used to form the formulations described below, without departing from the disclosure herein, as will be understood by those skilled in the art who have read the disclosure herein.

[0048] In some embodiments, the acid contained in the nicotine liquid formulation is determined by the vapor pressure of the acid. In some embodiments, the nicotine liquid formulation contains an acid with a vapor pressure similar to that of free base nicotine. In some embodiments, the nicotine liquid formulation is formed from an acid with a vapor pressure similar to that of free base nicotine at the heating temperature of the apparatus. As an unrestricted example, Figure 3 illustrates this trend. Nicotine salts formed from nicotine and benzoic acid; nicotine and pyruvate; nicotine and salicylic acid; or nicotine and levulinic acid are salts that produce satisfaction in individual use, consistent with the efficient transfer of nicotine and a rapid increase in nicotine plasma levels. This pattern may be due to the mechanism of action of the nicotine liquid formulation during heating. Nicotine salts may separate at or slightly below the heating temperature of the apparatus, resulting in a mixture of free base nicotine and individual acids. At this point, if both nicotine and acid have similar vapor pressures, they aerosolize simultaneously, resulting in the transfer of free base nicotine and constituent acids to the user. In some embodiments, a nicotine liquid formulation (e.g., a nicotine salt liquid formulation) may contain a nicotine salt in a bioacidible liquid carrier for heating in a cryoelectronic device (i.e., an e-cigarette) to produce an inhalable aerosol, and the acid used to form the nicotine salt is characterized by a vapor pressure between 20 and 4000 mmHg at 200°C. In some embodiments, the acid used to form the nicotine salt is characterized by a vapor pressure between 20 and 2000 mmHg at 200°C. In some embodiments, the acid used to form the nicotine salt is characterized by a vapor pressure between 100 and 300 mmHg at 200°C.

[0049] Unexpectedly, various liquid nicotine formulations produced varying levels of satisfaction in individuals. In some embodiments, higher protonation resulted in lower satisfaction compared to lower protonation, indicating that the range of protonation of the nicotine salt affects satisfaction. In some embodiments, nicotine (e.g., nicotine salt) in the formulation, vapor, and / or aerosol is mono-protonated. In some embodiments, nicotine (e.g., nicotine salt) in the formulation, vapor, and / or aerosol is di-protonated. In some embodiments, nicotine (e.g., nicotine salt) in the formulation, vapor, and / or aerosol exists in one or more protonation states, such as an equilibrium between mono-protonated and di-protonated nicotine salts. In some embodiments, the range of nicotine protonation depends on the nicotine:acid stoichiometric ratio used in the salt formation reaction. In some embodiments, the range of nicotine protonation depends on the solvent. In some embodiments, the range of nicotine protonation is unknown.

[0050] In some embodiments, monoprotonated nicotine salts have produced high satisfaction in users. For example, nicotine benzoates and nicotine salicylates are monoprotonated nicotine salts and produce high satisfaction in users. The reason for this tendency can be explained by the action of a mechanism in which nicotine is first protonated before being transferred to a vapor containing the constituent acid, then reprotonated and stabilized by the acid in the aerosol, and carried down the flow to the user's lungs by the acid. In addition, the lack of satisfaction with free base nicotine suggests that a second factor may be important. Depending on the salt, nicotine salts perform best when the nicotine salt is within the optimal range of protonation. For example, as depicted in Example 13 (not limited), nicotine benzoates transfer the maximum amount of nicotine to the aerosol at a 1:1 molar ratio of benzoic acid to nicotine. Lower molar ratios result in less nicotine being transferred to the aerosol, and ratios higher than 1:1 molar ratio of benzoic acid to nicotine do not result in further transfer of nicotine to the aerosol. This can be explained by the fact that 1 mole of nicotine must be associated with or interact with 1 mole of benzoic acid to form a salt. If there is not enough benzoic acid to associate with all the nicotine molecules, the free base nicotine that remains unprotonated in the formulation will vaporize, reducing user satisfaction.

[0051] In some embodiments, acids that decompose at room temperature or the operating temperature of a cryogenic electron vaporizer (i.e., a low-temperature e-cigarette) do not provide the same level of satisfaction to the user. For example, to transfer the same molar amount of acid from liquid to aerosol, twice the amount of malic acid decomposed at the operating temperature of a cryogenic e-cigarette is required compared to benzoic acid. Therefore, in some embodiments, in the non-gas phase of the aerosol, twice the amount of malic acid is required compared to benzoic acid to produce an aerosol containing the same molar amount of nicotine. Furthermore, since malic acid contains two carboxylic acid groups and benzoic acid contains one, when malic acid is used in a nicotine liquid formulation, four times the amount of acidic functional group hydrogen is required compared to benzoic acid. Furthermore, since malic acid contains two carboxylic acid groups and benzoic acid contains one, when malic acid is used in a nicotine liquid formulation, four times the amount of acidic functional group hydrogen is required compared to benzoic acid. In some embodiments, one or more chemical substances produced by the decomposition of the acid result in an undesirable experience for the user. In some embodiments, an undesirable experience includes flavor, a nervous response, and / or irritation of one or more parts of the mouth, upper respiratory tract, and / or lungs.

[0052] In some embodiments, provided herein are methods, systems, apparatus, formulations and kits for generating an inhalable aerosol containing nicotine for delivery to a user, using an electron vaporizer, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine, an acid, and a bioacceptable liquid carrier, and the method of using the e-cigarette comprises the steps of: supplying an amount of the nicotine liquid formulation to the heater; and heating the amount of the nicotine liquid formulation so that the heater forms an aerosol, wherein at least about 50% of the amount of the acid is present in the aerosol, and at least about 90% of the amount of the nicotine is present in the aerosol. In some embodiments, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least 95%, or at least about 99% of the amount of the acid is present in the aerosol. In some embodiments, at least about 50% to about 99% of the amount of the acid is present in the aerosol. In some embodiments, at least about 50% to about 95% of the acid in the amount is present in the aerosol. In some embodiments, at least about 50% to about 90% of the acid in the amount is present in the aerosol. In some embodiments, at least about 50% to about 80% of the acid in the amount is present in the aerosol. In some embodiments, at least about 50% to about 70% of the acid in the amount is present in the aerosol. In some embodiments, at least about 50% to about 60% of the acid in the amount is present in the aerosol. In some embodiments, at least about 60% to about 99% of the acid in the amount is present in the aerosol. In some embodiments, at least about 60% to about 95% of the acid in the amount is present in the aerosol. In some embodiments, at least about 60% to about 90% of the acid in the amount is present in the aerosol. In some embodiments, at least about 60% to about 80% of the acid in the amount is present in the aerosol.In some embodiments, at least about 60% to about 70% of the amount of the acid is present in the aerosol. In some embodiments, at least about 70% to about 99% of the amount of the acid is present in the aerosol. In some embodiments, at least about 70% to about 95% of the amount of the acid is present in the aerosol. In some embodiments, at least about 70% to about 90% of the amount of the acid is present in the aerosol. In some embodiments, at least about 70% to about 80% of the amount of the acid is present in the aerosol.

[0053] In some embodiments, the aerosol is delivered in particles of a size that can be delivered to the user's lungs (e.g., the alveoli of the user's lungs) via the mouth or nasal cavity. In some embodiments, the aerosol produced using a low-temperature vaporizer (e.g., a low-temperature e-cigarette) and a nicotine liquid formulation (e.g., a nicotine salt liquid formulation) is delivered in particles of a size that can be delivered to the user's lungs (e.g., the alveoli of the user's lungs) via the mouth or nasal cavity. In some embodiments, the absorption rate in the user's lungs (e.g., the alveoli of the user's lungs) is influenced by the aerosol particle size. In some embodiments, the aerosol particles are of the following sizes: approximately 0.1 microns to approximately 5 microns, approximately 0.1 microns to approximately 4.5 microns, approximately 0.1 microns to approximately 4 microns, approximately 0.1 microns to approximately 3.5 microns, approximately 0.1 microns to approximately 3 microns, approximately 0.1 microns to approximately 2.5 microns, approximately 0.1 microns to approximately 2 microns, approximately 0.1 microns to approximately 1.5 microns, approximately 0.1 microns to approximately 1 micron, approximately 0.1 microns to approximately 0.9 microns, approximately 0.1 microns to approximately 0.8 microns, approximately 0.1 microns to approximately 0.7 microns, approximately 0.1 microns to approximately 0.6 microns, approximately 0.1 microns to approximately 0.5 microns, approximately 0.1 microns to approximately 0.4 microns, approximately 0.1 microns to approximately 0.3 microns, and approximately 0.1 microns to approximately 0.2 microns. Up to approximately 0.2 microns to approximately 5 microns, approximately 0.2 microns to approximately 4.5 microns, approximately 0.2 microns to approximately 4 microns, approximately 0.2 microns to approximately 3.5 microns, approximately 0.2 microns to approximately 3 microns, approximately 0.2 microns to approximately 2.5 microns, approximately 0.2 microns to approximately 2 microns, approximately 0.2 microns to approximately 1.5 microns, approximately 0.2 microns to approximately 1 micron, approximately 0.2 microns to approximately 0.9 microns, approximately 0.2 microns to approximately 0.8 microns, approximately 0.2 microns to approximately 0.7 microns, approximately 0.2 microns to approximately 0.6 microns, approximately 0.2 microns to approximately 0.5 microns, approximately 0.2 microns to approximately 0.4 microns, approximately 0.2 microns to approximately 0.3 microns, approximately 0.3 microns to approximately 5 microns, approximately 0.3 microns to approximately 4.5 microns, approximately 0.3 microns to approximately 4 microns, approximately 0.3 microns to approximately 3.5 microns, approximately 0.3 microns to approximately 3 microns, approximately 0.3 microns to approximately 2.5 microns, approximately 0.3 microns to approximately 2 microns, approximately 0.3 microns to approximately 1.5 microns, approximately 0.3 microns to approximately 1 micron, approximately 0.3 microns to approximately 0.9 microns, approximately 0.3 microns to approximately 0.8 microns, approximately 0.3 microns to approximately 0.7 microns, approximately 0.3 microns to approximately 0.6 microns, approximately 0.3 microns to approximately 0.5 microns, approximately 0.3 microns From approximately 0.4 microns to approximately 5 microns, from approximately 0.4 microns to approximately 4.5 microns, from approximately 0.4 microns to approximately 4 microns, from approximately 0.4 microns to approximately 3.5 microns, from approximately 0.4 microns to approximately 3 microns, from approximately 0.4 microns to approximately 2.5 microns, from approximately 0.4 microns to approximately 2 microns, from approximately 0.4 microns to approximately 1.5 microns, from approximately 0.4 microns to approximately 1 micron, from approximately 0.4 microns to approximately 0.9 microns, from approximately 0.4 microns to approximately 0.8 microns, from approximately 0.4 microns to approximately 0.7 microns And, from approximately 0.4 microns to approximately 0.6 microns, from approximately 0.4 microns to approximately 0.5 microns, from approximately 0.5 microns to approximately 5 microns, from approximately 0.5 microns to approximately 4.5 microns, from approximately 0.5 microns to approximately 4 microns, from approximately 0.5 microns to approximately 3.5 microns, from approximately 0.5 microns to approximately 3 microns, from approximately 0.5 microns to approximately 2.5 microns, from approximately 0.5 microns to approximately 2 microns, from approximately 0.5 microns to approximately 1.5 microns, from approximately 0.5 microns to approximately 1 micron, from approximately 0.5 microns to approximately 0.9 microns, and approximately 0.5 microns. From approximately 0.8 microns, from approximately 0.5 microns to approximately 0.7 microns, from approximately 0.5 microns to approximately 0.6 microns, from approximately 0.6 microns to approximately 5 microns, from approximately 0.6 microns to approximately 4.5 microns, from approximately 0.6 microns to approximately 4 microns, from approximately 0.6 microns to approximately 3.5 microns, from approximately 0.6 microns to approximately 3 microns, from approximately 0.6 microns to approximately 2.5 microns, from approximately 0.6 microns to approximately 2 microns, from approximately 0.6 microns to approximately 1.5 microns, from approximately 0.6 microns to approximately 1 micron, and from approximately 0.6 microns to approximately 0.Up to 9 microns, approximately 0.6 to 0.8 microns, approximately 0.6 to 0.7 microns, approximately 0.8 to 5 microns, approximately 0.8 to 4.5 microns, approximately 0.8 to 4 microns, approximately 0.8 to 3.5 microns, approximately 0.8 to 3 microns, approximately 0.8 to 2.5 microns, approximately 0.8 to 2 microns, approximately 0.8 to 1.5 microns, approximately 0.8 to 1 micron, approximately 0.8 to 0.9 microns, approximately 0.9 to 5 microns, approximately 0.9 to 4.5 microns From approximately 0.9 microns to 4 microns, from approximately 0.9 microns to 3.5 microns, from approximately 0.9 microns to 3 microns, from approximately 0.9 microns to 2.5 microns, from approximately 0.9 microns to 2 microns, from approximately 0.9 microns to 1.5 microns, from approximately 0.9 microns to 1 micron, from approximately 1 micron to 5 microns, from approximately 1 micron to 4.5 microns, from approximately 1 micron to 4 microns, from approximately 1 micron to 3.5 microns, from approximately 1 micron to 3 microns, from approximately 1 micron to 2.5 microns, from approximately 1 micron to 2 microns, and from approximately 1 micron to 1.5 microns.

[0054] In some embodiments, the amount of the nicotine liquid formulation supplied to the heater includes volume or mass. In some embodiments, the amount is quantified "per breath". In some embodiments, the volume includes: about 1 μL, about 2 μL, about 3 μL, about 4 μL, about 5 μL, about 6 μL, about 7 μL, about 8 μL, about 9 μL, about 10 μL, about 15 μL, about 20 μL, about 25 μL, about 30 μL, about 35 μL, about 40 μL, about 45 μL, about 50 μL, about 60 μL, about 70 μL, about 80 μL, about 90 μL, about 100 μL, or more than about 100 μL. In some embodiments, the amount includes a mass of approximately 1 mg, approximately 2 mg, approximately 3 mg, approximately 4 mg, approximately 5 mg, approximately 6 mg, approximately 7 mg, approximately 8 mg, approximately 9 mg, approximately 10 mg, approximately 15 mg, approximately 20 mg, approximately 25 mg, approximately 30 mg, approximately 35 mg, approximately 40 mg, approximately 45 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, or more than approximately 100 mg.

[0055] The flavor of the constituent acids used in salt formation may be considered when selecting the acids. A suitable acid has minimal or no toxicity to humans at the concentration used. A suitable acid is compatible with the components of the e-cigarette that it comes into contact with or may come into contact with at the concentration used; that is, such an acid is not decomposed or otherwise reacted with the e-cigarette components it comes into contact with or may come into contact with. The aroma of the constituent acids used in salt formation may be considered when selecting a suitable acid. The concentration of nicotine salt in the carrier may affect satisfaction among individual users. In some embodiments, the flavor of the formulation is adjusted by changing the acid. In some embodiments, the flavor of the formulation is adjusted by adding exogenous flavoring agents. In some embodiments, acids with an unpleasant taste or odor are used in minimal amounts to mitigate such properties. In some embodiments, exogenous acids with a pleasant odor or taste are added to the formulation. Examples of salts that can supply flavor and aroma to the main aerosol at specific levels include nicotine acetate, nicotine oxalate, nicotine malate, nicotine isovalerate, nicotine lactate, nicotine citrate, nicotine phenylacetate, and nicotine myristicate.

[0056] Nicotine liquid formulations can generate an aerosol that can be inhaled by heating them in a cryoelectronic vaporizer (i.e., an e-cigarette). The amount of nicotine or nicotine salt aerosol inhaled can be determined by the user. The user can modify the amount of nicotine or nicotine salt inhaled, for example, by adjusting the inhalation strength.

[0057] The formulation is described herein as comprising two or more nicotine salts. In some embodiments of the formulation comprising two or more nicotine salts, each individual nicotine salt is formed as described herein.

[0058] A nicotine liquid formulation refers to a single nicotine salt or a mixture of nicotine salts, with other suitable chemical components used in e-cigarettes, such as carriers, stabilizers, diluents, dispersants, anti-settling agents, thickeners, and / or excipients, as used herein. In certain embodiments, the nicotine liquid formulation is stirred at ambient conditions for 20 minutes. In certain embodiments, the nicotine liquid formulation is heated and stirred at 55°C for 20 minutes. In certain embodiments, the nicotine liquid formulation is heated and stirred at 90°C for 60 minutes. In certain embodiments, the formulation facilitates the delivery of nicotine to a living organism (e.g., the lungs).

[0059] The nicotine in the nicotine liquid formulations provided herein is either naturally occurring nicotine (e.g., from an extract of a nicotine-containing species such as tobacco) or synthetic nicotine. In some embodiments, the nicotine is (-)-nicotine, (+)-nicotine, or a mixture thereof. In some embodiments, the nicotine is used in a relatively pure form (e.g., over 80% purity, 85% purity, 90% purity, 95% purity, or 99% purity). In some embodiments, the nicotine for the nicotine liquid formulations provided herein is visually "clear water" in order to avoid or minimize the formation of tarry residues during the subsequent salt formation process.

[0060] The nicotine liquid formulations used in the cryogenic volatile devices (i.e., e-cigarettes) described herein have, in some embodiments, nicotine concentrations ranging from about 0.5% (w / w) to about 20% (w / w), where this concentration is the weight of nicotine relative to the total weight of the solution (e.g., w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 1% (w / w) to about 20% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 1% (w / w) to about 18% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 1% (w / w) to about 15% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 4% (w / w) to about 12% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 1% (w / w) to about 18% (w / w), from about 3% (w / w) to about 15% (w / w), or from about 4% (w / w) to about 12% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 0.5% (w / w) to about 10% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 0.5% (w / w) to about 5% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 0.5% (w / w) to about 4% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have nicotine concentrations ranging from about 0.5% (w / w) to about 3% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 0.5% (w / w) to about 2% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 0.5% (w / w) to about 1% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 1% (w / w) to about 10% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 1% (w / w) to about 5% (w / w).In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 1% (w / w) to about 4% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 1% (w / w) to about 3% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 1% (w / w) to about 2% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 2% (w / w) to about 10% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 2% (w / w) to about 5% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration ranging from about 2% (w / w) to about 4% (w / w). Specific embodiments include approximately 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, and 3. The present invention provides nicotine liquid formulations having nicotine concentrations including 8%, 3.9%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% (w / w), or higher, or any increment. One embodiment provides a nicotine liquid formulation with a nicotine concentration of about 5% (w / w). Another embodiment provides a nicotine liquid formulation with a nicotine concentration of about 4% (w / w). Another embodiment provides a nicotine liquid formulation with a nicotine concentration of about 3% (w / w). Another embodiment provides a nicotine liquid formulation with a nicotine concentration of about 2% (w / w). One embodiment provides a nicotine liquid formulation with a nicotine concentration of approximately 1% (w / w). Another embodiment provides a nicotine liquid formulation with a nicotine concentration of approximately 0.5% (w / w).

[0061] The nicotine liquid formulations used in the cryogenic volatile devices (i.e., e-cigarettes) described herein have, in some embodiments, nicotine concentrations of approximately 0.5% (w / w), approximately 1% (w / w), approximately 2% (w / w), approximately 3% (w / w), approximately 4% (w / w), approximately 5% (w / w), approximately 6% (w / w), approximately 7% (w / w), approximately 8% (w / w), approximately 9% (w / w), approximately 10% (w / w), approximately 11% (w / w), approximately 12% (w / w), approximately 13% (w / w), approximately 14% (w / w), approximately 15% (w / w), approximately 16% (w / w), approximately 17% (w / w), approximately 18% (w / w), approximately 19% (w / w), or approximately 20% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine at the following concentrations: from about 0.5% (w / w) to about 20% (w / w), from about 0.5% (w / w) to about 18% (w / w), from about 0.5% (w / w) to about 15% (w / w), from about 0.5% (w / w) to about 12% (w / w), and about 0.5% (w / w). From approximately 10% (w / w), from approximately 0.5% (w / w) to approximately 8% (w / w), from approximately 0.5% (w / w) to approximately 7% (w / w), from approximately 0.5% (w / w) to approximately 6% (w / w), from approximately 0.5% (w / w) to approximately 5% (w / w), from approximately 0.5% (w / w) to approximately 4% (w / w), from approximately 0.5% (w / w) to approximately 3% (w / w), or from approximately 0.5% (w / w) to approximately 2% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatile device (i.e., e-cigarette) described herein contains nicotine at the following concentrations: from about 1% (w / w) to about 20% (w / w), from about 1% (w / w) to about 18% (w / w), from about 1% (w / w) to about 15% (w / w), from about 1% (w / w) to about 12% (w / w), and about 1% (w / w). From w to approximately 10% (w / w), from approximately 1% (w / w) to approximately 8% (w / w), from approximately 1% (w / w) to approximately 7% (w / w), from approximately 1% (w / w) to approximately 6% (w / w), from approximately 1% (w / w) to approximately 5% (w / w), from approximately 1% (w / w) to approximately 4% (w / w), from approximately 1% (w / w) to approximately 3% (w / w), or from approximately 1% (w / w) to approximately 2% (w / w).In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine in the following concentrations: from about 2% (w / w) to about 20% (w / w), from about 2% (w / w) to about 18% (w / w), from about 2% (w / w) to about 15% (w / w), from about 2% (w / w) to about 12% (w / w), from about 2% (w / w) to about 10% (w / w), from about 2% (w / w) to about 8% (w / w), from about 2% (w / w) to about 7% (w / w), from about 2% (w / w) to about 6% (w / w), from about 2% (w / w) to about 5% (w / w), from about 2% (w / w) to about 4% (w / w), or from about 2% (w / w) to about 3% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine in the following concentrations: from about 3% (w / w) to about 20% (w / w), from about 3% (w / w) to about 18% (w / w), from about 3% (w / w) to about 15% (w / w), from about 3% (w / w) to about 12% (w / w), from about 3% (w / w) to about 10% (w / w), from about 3% (w / w) to about 8% (w / w), from about 3% (w / w) to about 7% (w / w), from about 3% (w / w) to about 6% (w / w), from about 3% (w / w) to about 5% (w / w), or from about 3% (w / w) to about 4% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine in the following concentrations: from about 4% (w / w) to about 20% (w / w), from about 4% (w / w) to about 18% (w / w), from about 4% (w / w) to about 15% (w / w), from about 4% (w / w) to about 12% (w / w), from about 4% (w / w) to about 10% (w / w), from about 4% (w / w) to about 8% (w / w), from about 4% (w / w) to about 7% (w / w), from about 4% (w / w) to about 6% (w / w), or from about 4% (w / w) to about 5% (w / w).In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine in the following concentrations: from about 5% (w / w) to about 20% (w / w), from about 5% (w / w) to about 18% (w / w), from about 5% (w / w) to about 15% (w / w), from about 5% (w / w) to about 12% (w / w), from about 5% (w / w) to about 10% (w / w), from about 5% (w / w) to about 8% (w / w), from about 5% (w / w) to about 7% (w / w), or from about 5% (w / w) to about 6% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine at concentrations of approximately 6% (w / w) to approximately 20% (w / w), approximately 6% (w / w) to approximately 18% (w / w), approximately 6% (w / w) to approximately 15% (w / w), approximately 6% (w / w) to approximately 12% (w / w), approximately 6% (w / w) to approximately 10% (w / w), approximately 6% (w / w) to approximately 8% (w / w), and approximately 6% (w / w) to approximately 7% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatile devices (i.e., e-cigarettes) described herein contains nicotine at concentrations of approximately 2% (w / w) to approximately 6% (w / w). In some embodiments, the nicotine liquid formulation used in the cryogenic volatilizer (i.e., e-cigarette) described herein contains nicotine at a concentration of about 5% (w / w).

[0062] In some embodiments, the formulation further comprises one or more flavoring agents. In some embodiments, the flavor of the formulation is adjusted by modification of the acid. In some embodiments, the flavor of the formulation is adjusted by adding exogenous flavoring agents. In some embodiments, acids having an unpleasant taste or odor are used in minimal amounts to mitigate such properties. In some embodiments, exogenous acids having a pleasant odor or taste are added to the formulation. Examples of salts that can supply flavor and aroma to the main aerosol at a particular level include nicotine acetate, nicotine oxalate, nicotine malate, nicotine isovalerate, nicotine lactate, nicotine citrate, nicotine phenylacetate, and nicotine myristicate.

[0063] In some embodiments, the acid suitable for the nicotine liquid formulation has a vapor pressure of >20 mmHg at 200°C and does not corrode the e-cigarette or is non-toxic to humans. In some embodiments, the acid suitable for nicotine salt formation is selected from the group consisting of salicylic acid, formic acid, sorbic acid, acetic acid, benzoic acid, pyruvic acid, lauric acid, and levulinic acid.

[0064] In some embodiments, the acid suitable for the nicotine liquid formulation has a vapor pressure of 20-200 mmHg at 200°C and is non-corrosive to e-cigarettes or non-toxic to humans. In some embodiments, the acid suitable for nicotine salt formation is selected from the group consisting of salicylic acid, benzoic acid, lauric acid, and levulinic acid.

[0065] In some embodiments, the acid suitable for the nicotine liquid formulation has a melting point <160°C, a boiling point >160°C, a difference of at least 50°C between the melting point and the boiling point, does not corrode the e-cigarette, or is non-toxic to humans. In some embodiments, the acid suitable for nicotine salt formation has a melting point at least 40°C lower than the operating temperature of the e-cigarette, a boiling point lower than 40°C or less than the operating temperature of the e-cigarette, a difference of at least 50°C between the melting point and the boiling point, does not corrode the e-cigarette, or is non-toxic to humans, and the operating temperature is 200°C. In some embodiments, the acid suitable for nicotine salt formation is selected from the group consisting of salicylic acid, sorbic acid, benzoic acid, pyruvic acid, lauric acid, and levulinic acid.

[0066] In some embodiments, the acid suitable for nicotine liquid formulations does not decompose at the operating temperature of the e-cigarette. In some embodiments, the acid suitable for nicotine salt formation does not oxidize at the operating temperature of the e-cigarette. In some embodiments, the acid suitable for nicotine salt formation does not oxidize at room temperature. In some embodiments, the acid suitable for nicotine salt formation does not produce an unpleasant taste. In some embodiments, the acid suitable for nicotine salt formation has high solubility in liquid formulations used in cryogenic electron vaporizers (i.e., e-cigarettes).

[0067] The cryogenic electron vaporizer, i.e., e-cigarette 2, provided herein has a fluid storage compartment 4 containing an embodiment of a nicotine liquid formulation of any embodiment described herein. An embodiment is shown in Figure 4. The e-cigarette 2 in Figure 4 includes a mouth end 6 and a charging end 8. The mouth end 6 includes a mouthpiece 10. The charging end 8 may be connected to a battery or a charger or both, where the battery is inside the e-cigarette body and the charger is separate from the battery and connects to the body or battery to charge the battery. In some embodiments, the e-cigarette includes a rechargeable battery inside the e-cigarette body 14, and the charging end 8 includes a connector 12 for charging the rechargeable battery. In some embodiments, the e-cigarette includes a cartomizer which includes a fluid storage compartment and an atomizer. In some embodiments, the atomizer includes a heater. In some embodiments, the fluid storage compartment 4 is separable from the atomizer. In some embodiments, the fluid storage compartment 4 is replaceable as part of a replaceable cartridge. In some embodiments, the fluid storage compartment 4 is refillable. In some embodiments, the mouthpiece 10 is replaceable.

[0068] Provided herein is a cartomizer 18 having a fluid storage compartment 4 for a cryogenic electron vaporizer, i.e., an e-cigarette 2, which contains embodiments of the nicotine liquid formulation described herein within the fluid storage compartment described herein. The embodiment of the cartomizer 18 in Figure 5 includes a mouth end 6 and a connecting end 16. The connecting end 16 in the embodiment of Figure 5 connects the cartomizer 14 to a cryogenic electron vaporizer, i.e., an e-cigarette, or the battery of an e-cigarette, or both. The mouth end 6 includes a mouthpiece 10. In some embodiments, the cartomizer does not include a mouthpiece, and in such embodiments, the cartomizer can be coupled to the mouthpiece of the cryogenic electron vaporizer, i.e., an e-cigarette, or the mouthpiece can be coupled to the battery or body of the e-cigarette, while the cartomizer can be coupled to the cryogenic electron vaporizer, i.e., the battery or body of the e-cigarette. In some embodiments, the mouthpiece is essential to the body of the e-cigarette. In some embodiments, including the embodiment of Figure 5, the cartomizer 18 includes a fluid storage compartment 4 and an atomizer (not shown). In some embodiments, the atomizer includes a heater (not shown). [Examples]

[0069] <Example 1: Preparation of a nicotine liquid formulation> Various nicotine liquid formulations were prepared and added to a solution of propylene glycol (PG) / vegetable glycerin (VG) in a 3:7 ratio by weight, and thoroughly mixed. The examples shown below were used to prepare 10 g of each formulation. All procedures are scale-adjustable.

[0070] For example, the following procedure was applied to each individual formulation to prepare a nicotine liquid formulation having a final equivalent concentration of 2% (w / w) of nicotine free base. - Nicotine benzoate preparation: 0.15 g of benzoic acid was added to a beaker, and then 0.2 g of nicotine was added to the same beaker. The mixture was stirred at 55°C for 20 minutes until the benzoic acid was completely dissolved, forming an orange oily mixture. The mixture was cooled to ambient temperature. 9.65 g of PG / VG (3:7) solution was added to the orange nicotine benzoate, and the mixture was stirred until a visually homogeneous formulation solution was achieved. - The nicotine benzoate preparation can also be prepared by adding 0.15 g of benzoic acid to a beaker, and then adding 0.2 g of nicotine and 9.65 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 55°C for 20 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine citrate preparation was prepared by adding 0.47 g of citric acid to a beaker, then adding 0.2 g of nicotine and 9.33 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine malate preparation was prepared by adding 0.33 g of malic acid to a beaker, and then adding 0.2 g of nicotine and 9.47 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine succinate preparation was prepared by adding 0.29 g of succinic acid to a beaker, and then adding 0.2 g of nicotine and 9.51 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine salicylate preparation was prepared by adding 0.17 g of salicylic acid to a beaker, then adding 0.2 g of nicotine and 9.63 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine salicylate preparation can also be prepared by adding 0.17 g of salicylic acid to a beaker, and then adding 0.2 g of nicotine to the same beaker. The mixture was stirred at 90°C for 60 minutes until the salicylic acid was completely dissolved, and an orange oily mixture was formed. The mixture was then cooled to ambient conditions or maintained at 90°C when 9.63 g of PG / VG (3:7) solution was added. The mixture was then stirred at 90°C until a visually homogeneous formulation solution was achieved without any undissolved chemicals. - The nicotine-free base preparation was prepared by adding 0.2 g of nicotine to a beaker and then adding 9.8 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred under ambient conditions for 10 minutes until a visually homogeneous preparation solution was achieved.

[0071] For example, the following procedure was applied to each individual formulation to prepare a nicotine liquid formulation having a final equivolute concentration of 3% (w / w) nicotine free base. - Nicotine benzoate preparation: 0.23 g of benzoic acid was added to a beaker, and then 0.3 g of nicotine was added to the same beaker. The mixture was stirred at 55°C for 20 minutes until the benzoic acid was completely dissolved, forming an orange oily mixture. The mixture was cooled to ambient temperature. 9.47 g of PG / VG (3:7) solution was added to the orange nicotine benzoate salt, and the mixture was stirred until a visually homogeneous preparation solution was achieved. - The nicotine benzoate preparation can also be prepared by adding 0.23 g of benzoic acid to a beaker, and then adding 0.3 g of nicotine and 9.47 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 55°C for 20 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine citrate preparation was prepared by adding 0.71 g of citric acid to a beaker, and then adding 0.3 g of nicotine and 8.99 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine malate preparation was prepared by adding 0.5 g of malic acid to a beaker, then adding 0.3 g of nicotine and 9.2 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine levulinate preparation was prepared by adding 0.64 g of levulinic acid dissolved in a beaker, and then adding 0.3 g of nicotine to the same beaker. The mixture was stirred under ambient conditions for 10 minutes. An exothermic reaction occurred, producing an oily product. The mixture was allowed to cool to ambient temperature, and 9.06 g of PG / VG (3:7) solution was added to the same beaker. The mixture was then stirred under ambient conditions for 20 minutes until a visually homogeneous preparation solution was achieved. - The nicotine pyruvate formulation was prepared by adding 0.33 g of pyruvate to a beaker, and then adding 0.3 g of nicotine to the same beaker. The mixture was stirred under ambient conditions for 10 minutes. An exothermic reaction occurred, producing an oily product. The mixture was cooled to ambient temperature, and 9.37 g of PG / VG (3:7) solution was added to the same beaker. The mixture was then stirred under ambient conditions for 20 minutes until a visually homogeneous formulation solution was achieved. - The nicotine succinate preparation was prepared by adding 0.44 g of succinic acid to a beaker, and then adding 0.3 g of nicotine and 9.26 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine salicylate preparation was prepared by adding 0.26 g of salicylic acid to a beaker, and then adding 0.3 g of nicotine and 9.44 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine salicylate preparation can also be prepared by adding 0.26 g of salicylic acid to a beaker, and then adding 0.3 g of nicotine to the same beaker. The mixture was stirred at 90°C for 60 minutes until the salicylic acid was completely dissolved and an orange oily mixture was formed. The mixture was then cooled to ambient conditions or maintained at 90°C when 9.44 g of PG / VG (3:7) solution was added. The mixture was then stirred at 90°C until a visually homogeneous preparation solution was achieved without any dissolving chemicals. - The nicotine-free base preparation was prepared by adding 0.3 g of nicotine to a beaker, and then adding 9.7 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred under ambient conditions for 10 minutes until a visually homogeneous preparation solution was achieved.

[0072] For example, the following procedure was applied to each individual formulation to prepare a nicotine liquid formulation having a final equivolute concentration of 4% (w / w) nicotine free base. - Nicotine benzoate preparation: 0.3 g of benzoic acid was added to a beaker, and then 0.4 g of nicotine was added to the same beaker. The mixture was stirred at 55°C for 20 minutes until the benzoic acid was completely dissolved and an orange oily mixture was formed. The mixture was then cooled to ambient temperature. 9.7 g of PG / VG (3:7) solution was added to the orange nicotine benzoate, and the mixture was stirred until a visually homogeneous preparation solution was achieved. -Nicotine benzoate formulations can also be prepared by adding 0.3 g of benzoic acid to a beaker, and then adding 0.4 g of nicotine and 9.7 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 55°C for 20 minutes until a visually homogeneous formulation solution was achieved without any undissolved chemicals. For example, the following procedure was applied to each individual formulation to prepare a nicotine liquid formulation with a final equivolute concentration of 5% (w / w) of free nicotine base. - Nicotine benzoate preparation: 0.38 g of benzoic acid was added to a beaker, and then 0.5 g of nicotine was added to the same beaker. The mixture was stirred at 55°C for 20 minutes until the benzoic acid was completely dissolved and an orange oily mixture was formed. The mixture was then cooled to ambient temperature. 9.12 g of PG / VG (3:7) solution was added to the orange nicotine benzoate, and the mixture was stirred until a visually homogeneous preparation solution was achieved. -Nicotine benzoate preparations can also be prepared by adding 0.5 g of nicotine to a beaker, and then adding 9.12 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 55°C for 20 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine malate preparation can be prepared by adding 0.83 g of malic acid to a beaker, and then adding 0.5 g of nicotine and 8.67 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine levulinate preparation was prepared by adding 1.07 g of levulinic acid dissolved in a beaker, and then adding 0.5 g of nicotine to the same beaker. The mixture was stirred under ambient conditions for 10 minutes. An exothermic reaction occurred, producing an oily product. The mixture was cooled to ambient temperature, and 8.43 g of PG / VG (3:7) solution was added to the same beaker. The mixture was then stirred under ambient conditions for 20 minutes until a visually homogeneous preparation solution was achieved. - The nicotine pyruvate preparation was prepared by adding 0.54 g of pyruvate to a beaker, and then adding 0.5 g of nicotine to the same beaker. The mixture was stirred under ambient conditions for 10 minutes. An exothermic reaction occurred, producing an oily product. The mixture was cooled to ambient temperature, and 8.96 g of PG / VG (3:7) solution was added to the same beaker. The mixture was then stirred under ambient conditions for 20 minutes until a visually homogeneous preparation solution was achieved. - The nicotine succinate preparation was prepared by adding 0.73 g of succinic acid to a beaker, and then adding 0.5 g of nicotine and 8.77 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine salicylate preparation was made by adding 0.43 g of salicylic acid to a beaker, and then adding 0.5 g of nicotine and 9.07 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogeneous preparation solution was achieved without any undissolved chemicals. - The nicotine salicylate preparation can also be prepared by adding 0.43 g of salicylic acid to a beaker, and then adding 0.5 g of nicotine to the same beaker. The mixture was stirred at 90°C for 60 minutes until the salicylic acid was completely dissolved and an orange oily mixture was formed. The mixture was then cooled to ambient conditions or maintained at 90°C when 9.07 g of PG / VG (3:7) solution was added. The mixture was then stirred at 90°C until a visually homogeneous formulation solution was achieved without any undissolved chemicals. - The nicotine-free base preparation was prepared by adding 0.5 g of nicotine to a beaker, and then adding 9.5 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred under ambient conditions for 10 minutes until a visually homogeneous preparation solution was achieved. Various formulations containing various nicotine salts may be similar, or different concentrations of the above-mentioned liquid nicotine formulations, or other nicotine formulations may be prepared as can be understood by those skilled in the art who have read the disclosures herein.

[0073] Various formulations containing two or more nicotine salts can similarly be prepared in a 3:7 ratio solution of propylene glycol (PG) / vegetable glycerin (VG). For example, 0.43 g of nicotine levulinate (2.5% w / w nicotine) and 0.34 g of nicotine acetate (2.5% w / w nicotine) were added to 9.23 g of PG / VG solution to achieve a 5% w / w nicotine liquid formulation.

[0074] Furthermore, another typical formulation is provided. For example, 0.23 g of nicotine benzoate (1.33% w / w nicotine) (molar ratio 1:1 nicotine / benzoic acid), 0.25 g of nicotine salicylate (1.33% w / w nicotine) (molar ratio 1:1 nicotine / salicylic acid), and 0.28 g of nicotine pyruvate (1.34% w / w nicotine) (molar ratio 1:2 nicotine / pyruvic acid) were added to 9.25 g of PG / VG solution to achieve a 5% w / w nicotine liquid formulation.

[0075] <Example 2: Heart rate study related to nicotine solution via e-cigarette> Typical control formulations of nicotine levulinate, nicotine benzoate, nicotine succinate, nicotine salicylate, nicotine malate, nicotine pyruvate, nicotine citrate, nicotine free base, and propylene glycol were prepared and administered in the same manner to the same human subjects using a cryoelectronic volatilizer, i.e., an e-cigarette. Approximately 0.5 ml of each solution was loaded into the "eRoll" cartridge atomizer (joyetech.com) used in this study. The atomizer was then connected to an "eRoll" e-cigarette (same manufacturer). The operating temperature was approximately 150°C to 250°C, or approximately 180°C to 220°C.

[0076] Heart rate measurements were taken for 6 minutes; from 1 minute before inhalation began, through 3 minutes during inhalation, and 2 minutes after inhalation ended. Test participants took 10 puffs in 3 minutes in each case. The baseline heart rate was the average heart rate during the first minute before inhalation began. Heart rates after inhalation were averaged over 20-second intervals. Inhalations occurred every 20 seconds for a total of 3 minutes. Normalized heart rate was defined as the ratio between individual heart rate data points and the baseline heart rate. The final results are shown in Figure 1 as the normalized heart rate for the first 4 minutes.

[0077] Figure 1 summarizes the results from heart rate measurements obtained with various nicotine liquid formulations. For ease of reference when viewing Figure 1, at 180 seconds, from top to bottom (highest normalized heart rate to lowest normalized heart rate), the nicotine liquid formulations are as follows: nicotine salicylate, nicotine malate, nicotine levulinate (as a second reference point, as it is almost identical to the nicotine malate formulation at 180 seconds: at 160 seconds, the curve for the nicotine malate formulation is lower than the curve for the nicotine levulinate formulation), nicotine pyruvate, nicotine benzoate, nicotine citrate, nicotine succinate, and nicotine free base formulation. The bottom curve (lowest normalized heart rate) at 180 seconds is related to the placebo (100% propylene glycol). Test formulations containing nicotine salts cause a faster and more significant increase in heart rate than the placebo. When compared to nicotine-free base formulations with the same amount of nicotine by weight, test formulations containing nicotine salts cause a faster and more significant increase. In addition, nicotine salts (e.g., nicotine benzoate and nicotine pyruvate) prepared from acids with calculated vapor pressures between 20-200 mmHg at 200°C (excluding pyruvate (boiling point at 165°C) and benzoic acid (171.66 mmHg) respectively) cause a faster increase in heart rate than others. Nicotine salts (e.g., nicotine levulinate, nicotine benzoate, and nicotine salicylate) prepared from acids (benzoic acid, levulinic acid, and salicylic acid, respectively) cause an even more significant increase in heart rate. Therefore, other suitable nicotine salts formed by acids with similar vapor pressures and / or similar boiling points may be used in accordance with the implementation of the present invention. This experience of increased heart rate, which is theoretically comparable to conventional burning tobacco, has not been demonstrated or confirmed in other e-cigarette devices. Even when nicotine salts (solutions of nicotine salts with a concentration of 20 w / w or higher) are used as additives to tobacco, their effectiveness in low-temperature tobacco vaporization devices (e-cigarettes) that do not burn tobacco has not been demonstrated or confirmed. Therefore, the results from this experiment were surprising and unpredictable.

[0078] <Example 3: A study on satisfaction with nicotine-containing saline solution via e-cigarettes> In addition to the heart rate study shown in Example 2, a nicotine liquid formulation (using a 3% w / w nicotine liquid formulation as described in Example 1) was used to conduct a satisfaction study using 11 test participants. Test participants, cryoelectronic devices (i.e., e-cigarettes), and / or conventional tobacco users were required to abstain from nicotine intake for at least 12 hours prior to the test. Participants used a cryoelectronic device (i.e., e-cigarette) and took 10 puffs over 3 minutes in each case (as used in Example 2), and were then asked to rate the level of physical and emotional satisfaction they felt on a scale of 0-10, with 0 being not physically or emotionally satisfied. The formulations were then ranked from 1-8, with 1 being the highest rank and 8 being the lowest rank, using the rank provided for each formulation. The ranks of each formulation were then averaged across the 11 participants to generate the average rank in Table 1. Nicotine benzoate, nicotine pyruvate, nicotine salicylate, and nicotine levulinate all showed good performance, followed by nicotine malate, nicotine succinate, and nicotine citrate.

[0079] [Table 1]

[0080] Based on satisfaction studies, nicotine salt preparations with acids having vapor pressures between >20 mmHg@200°C, 20-200 mmHg@200°C, or 100-300 mmHg@200°C provide more satisfaction than others (except pyruvate, which has a boiling point of 165°C). For reference, salicylic acid was measured to have a vapor pressure of approximately 135.7 mmHg@200°C, benzoic acid approximately 171.7 mmHg@200°C, and levulinic acid approximately 149 mmHg@200°C.

[0081] Based on the satisfaction studies, nicotine liquid formulations, such as nicotine salt liquid formulations, were ranked lower if they contained acids that decompose at the operating temperature of the device (i.e., malic acid). However, nicotine liquid formulations, such as nicotine salt liquid formulations, were ranked higher if they contained acids that do not decompose at the operating temperature of the device (i.e., benzoic acid). Therefore, acids that tend to decompose at the operating temperature of the device are undesirable compared to acids that do not tend to decompose.

[0082] <Example 4: Test Formulation 1 (TF1)> The nicotine levulinate solution used in glycerin containing nicotine salts was as follows: 1.26 g (12.6% w / w) of nicotine levulinate in a 1:3 ratio, and 8.74 g (87.4% w / w) of glycerin - total weight 10.0 g.

[0083] Neat nicotine levulinate was added to glycerin and thoroughly mixed. L-nicotine had a molar mass of 162.2 g, and levulinate had a molar mass of 116.1 g. At a 1:3 molar ratio, the percentage of nicotine by weight in nicotine levulinate is obtained from: 162.2 g / (162.2 g + (3 × 116.1 g)) = 31.8% (w / w).

[0084] <Example 5: Test Formulation 2 (TF2)> A solution of free base nicotine in glycerin containing 0.40 g (4.00% w / w) L-nicotine was dissolved in 9.60 g (96.0% w / w) glycerin and thoroughly mixed.

[0085] <Example 6: Heart rate study related to nicotine solution via e-cigarette> Both formulations (TF1 and TF2) were administered to the same human subjects in the same manner using a cryoelectronic vaporizer (i.e., e-cigarette): approximately 0.6 ml of each solution was loaded into an "eGo-C" cartridge atomizer (joyetech.com). The atomizer was then coupled to an "eVic" e-cigarette (same manufacturer). This model of e-cigarette allows for adjustable voltage and therefore wattage via the atomizer. The operating temperature of the e-cigarette is approximately 150°C to 250°C or approximately 180°C to 220°C.

[0086] In both cases, the atomizer has a resistance of 2.4 ohms, the e-cigarette is set to 4.24V, and it delivers a power of 7.49W. (P=V^2 / R)

[0087] Heart rate was measured at 10-minute 30-second intervals from the start of inhalation. In each case, test participants took 10 puffs in 3 minutes (solid line: (second highest peak): tobacco, dark dotted line (highest peak): test formulation 1 (TF1 nicotine liquid formulation) (light dotted line): test formulation 2 (TF2 nicotine liquid formulation). A comparison between tobacco and TF1 and TF2 is shown in Figure 2.

[0088] Figure 2 clearly shows that the test formulation containing nicotine levulinate (TF1) resulted in a faster increase in heart rate than nicotine alone (TF2). Furthermore, TF1 more closely resembled the increase rate of tobacco. Other salts were also tried and were found to increase heart rate compared to a pure nicotine solution. Therefore, other suitable nicotine salts that produce similar results may be used in accordance with the implementation of the present invention, such as other keto acids (alpha-keto acids, beta-keto acids, gamma-keto acids, etc.) such as pyruvate, oxaloacetate, and acetoacetate. This experience of increased heart rate comparable to that of conventional burning tobacco has not been demonstrated or identified in other e-cigarette devices. Nor has it been demonstrated or identified in low-temperature tobacco vaporizers that do not burn tobacco, even when nicotine salts were used as additives to tobacco (solutions of nicotine salts of 20% (W / W) or higher). Therefore, the results from this experiment were surprising and unexpected.

[0089] In addition, the data appears to correlate well with previous findings shown in Figure 2.

[0090] As previously described in satisfaction studies, nicotine salt formulations containing acids with a vapor pressure between 20-300 mmHg@200°C provide greater satisfaction than others, except for nicotine liquid formulations made with pyruvate, which has a boiling point of 165°C, as shown in Figure 3. Furthermore, based on satisfaction studies, nicotine liquid formulations containing acids that decompose at the operating temperature of the apparatus (i.e., malic acid), such as nicotine salt liquid formulations, are ranked lower, while nicotine liquid formulations containing acids that do not decompose at the operating temperature of the apparatus (i.e., benzoic acid), such as nicotine salt liquid formulations, are ranked higher. Therefore, acids that tend to decompose at the operating temperature of the apparatus are less preferable than acids that do not tend to decompose. Based on the findings herein, these nicotine liquid formulations are expected to have one or more of the following properties: Vapor pressure between -20-300 mmHg at 200°C -> Vapor pressure at 20mmHg@200℃, - A difference of at least 50°C between the boiling point and the melting point, a boiling point higher than 160°C, and a melting point below 160°C. - A difference of at least 50°C between the boiling point and the melting point, a boiling point higher than 160°C, and a melting point below 160°C. - A difference of at least 50°C between the boiling point and the melting point, a boiling point up to 40°C lower than the operating temperature, and a melting point at least 40°C lower than the operating temperature, - It is resistant to decomposition due to the operating temperature of the device.

[0091] Tmax - Time to Maximum Blood Concentration: Based on the results established herein, users of cryoelectronic devices (i.e., e-cigarettes) containing nicotine liquid formulations experience a comparable rate of physical and emotional satisfaction from the use of formulations containing a mixture of nicotine salts prepared with appropriate acids, at least 1.2 to 3 times faster than when using formulations containing free base nicotine. As shown in Figure 1: Nicotine from nicotine salt formulations appeared to produce a heartbeat of approximately 1.2 times the individual's normal heart rate approximately 40 seconds after inhalation; nicotine from nicotine free base formulations appeared to produce a heartbeat of approximately 1.2 times the individual's normal heart rate approximately 110 seconds after inhalation; however, there is a 2.75-fold difference in the time to achieve a comparable initial satisfaction.

[0092] Furthermore, this is not inconsistent with the data from Figure 2; here, the data illustrates that in approximately 120 seconds (2 minutes), the test participants' heart rates reached a maximum of 105-110 bpm with either conventional cigarettes or liquid nicotine formulation (TF1); the heart rates of these same participants reached a maximum of approximately 86 bpm in approximately 7 minutes with free nicotine base formulation (TF2); and there was a 1.2-fold greater effect difference between free base and nicotine salt (and conventional cigarettes).

[0093] Furthermore, considering the peak satisfaction (achieved approximately 120 seconds after inhalation (time=0)) and the gradient of the normalized heart rate line, the approximate gradients of these nicotine liquid formulations over free base nicotine formulations are in the range of 0.0054 hrn / sec and 0.0025 hrn / sec. For comparison, the gradient of the line for free base nicotine liquid formulations is approximately 0.002. This would suggest that the concentration of nicotine available to the user is delivered 1.25 to 2.7 times faster than that of free base formulations.

[0094] In another measurement criterion; Cmax—maximum blood nicotine concentration; as illustrated above, a similar rate of increase is expected to be measured in blood nicotine concentration. That is, comparable Cmaxes are obtained between general tobacco and specific nicotine liquid formulations, but it is expected, based on the findings herein, that free base nicotine solutions will have lower Cmaxes, which could not be predicted based on known techniques to date.

[0095] Similarly, it was anticipated based on the findings herein that certain nicotine liquid formulations would have a higher rate of nicotine uptake into the blood in the first half of the time, and not based on known technologies to date. Indeed, Example 8 shows data for two salt formulations that are consistent with these predictions, which were not predictable compared to technologies available to date, based on the findings and tests described herein.

[0096] <Example 7: Heart rate study related to nicotine solution via e-cigarette> As described in Example 1, typical control formulations of nicotine levulinate, nicotine benzoate, nicotine succinate, nicotine salicylate, nicotine malate, nicotine pyruvate, nicotine citrate, nicotine sorbate, nicotine laurate, nicotine free base, and propylene glycol were prepared and administered to the same human subjects in the same manner using a cryoelectronic vaporizer, i.e., an e-cigarette. Approximately 0.5 ml of each solution was loaded into the "eRoll" cartridge atomizer (joyetech.com) used in this study. The atomizer was then coupled to an "eRoll" e-cigarette (same manufacturer). The operating temperature of the e-cigarette was approximately 150°C to approximately 250°C or approximately 180°C to approximately 220°C.

[0097] Heart rate measurements were taken for 6 minutes; from 1 minute before inhalation began, through 3 minutes during inhalation, and 2 minutes after inhalation ended. Each participant took 10 puffs in 3 minutes in each case. The baseline heart rate was the average heart rate during the first minute before inhalation began. Heart rates after inhalation were averaged over 20-second intervals. Normalized heart rate was defined as the ratio between individual heart rate data points and the baseline heart rate. Final results were presented as normalized heart rate.

[0098] <Example 8: Blood concentration test> Blood concentration tests were performed on 24 subjects (n=24). Four test substances were used in this study: one reference cigarette and three nicotine liquid formulations used in a cryoelectronic device (i.e., e-cigarette), which have e-cigarette operating temperatures of approximately 150°C to 250°C, or approximately 180°C to 220°C. The reference cigarette was Pall Mall (New Zealand). Three nicotine liquid formulations were tested in an e-cigarette: 2% free base (w / w based on nicotine), 2% benzoate (w / w based on nicotine, 1:1 molar ratio of nicotine to benzoate), and 2% malate (w / w based on nicotine, 1:2 molar ratio of nicotine to malate). The three nicotine liquid formulations were liquid formulations prepared as described in Example 1.

[0099] The nicotine concentration of each formulation was confirmed using a UV spectrophotometer (Cary 60 manufactured by Agilent). Sample solutions for UV analysis were prepared by dissolving 20 mg of each formulation in 20 ml of 0.3% HCl in water. The sample solutions were then scanned with a UV spectrophotometer, and the characteristic nicotine peak at 259 nm was used to measure the amount of nicotine in the sample relative to a standard solution of 19.8 μg / ml nicotine in the same diluent. The standard solution was prepared by first dissolving 19.8 mg of nicotine in 10 ml of 0.3% HCl in water, and then diluting it 1:100 with 0.3% HCl in water. The reported nicotine concentrations for all formulations were within the range of 95-105% of the required concentration.

[0100] All subjects were able to consume 30-55 mg of the liquid formulation of each tested mixture using an e-cigarette.

[0101] Literature results: C. Bullen et al, Tobacco Control 2010, 19:98-103 Tobacco (5 minutes, arbitrary (adlib), n=9): Tmax=14.3 (8.8-19.9), Cmax=13.4 (6.5-20.3) 1.4%E-cig (5 minutes arbitrary, n=8): Tmax=19.6(4.9-34.2), Cmax=1.3(0.0-2.6) Nicorette inhaler (20 mg / 20 mins, n=10): Tmax=32.0 (18.7-45.3), Cmax=2.1 (1.0-3.1).

[0102] Cmax evaluation of a 2% nicotine blend: Cmax = Mass consumed * Strength * Bioavailability / (Volume of distribution * Body * Weight) = 40 mg * 2% * 80% / (2.6 L / kg * 75 kg) = 3.3 ng / mL

[0103] The Cmax of a 4% nicotine blend was evaluated: Cmax = Mass consumed * Strength * Bioavailability / (Volume of distribution * Body * Weight) = 40 mg * 4% * 80% / (2.6 L / kg * 75 kg) = 6.6 ng / mL

[0104] The pharmacokinetic profiles of the blood concentration tests are shown in Figure 6; they show the blood nicotine concentration (ng / ml) over time after the first puff (inhalation) of the aerosol from the e-cigarette or after smoking the reference tobacco. Ten puffs were performed with 30-second intervals, starting at time=0 and continuing for 4.5 minutes. It appears that, based on the data shown in Figure 6, the free base formulation appears to be statistically different with respect to Cmax from the salt formulation and / or reference tobacco, as in other studies herein, the free base formulation appears to be lower than others tested at multiple time points. Furthermore, those skilled in the art can appropriately be inspired to conduct tests to determine statistically based differences between one or more formulations and tobaccos, or between these formulations in cryoelectronic vaporizers, i.e., e-cigarettes, by looking at the disclosures herein. For ease of reference, Table 2 shows the amount of nicotine detected in each formulation and reference tobacco (as the average for all users), presented in ng / mL along with Cmax and Tmax. The data from these tables, therefore, along with the raw data, were used to generate Figures 6, 7, and 8.

[0105] [Table 2-1]

[0106] [Table 2-2]

[0107] Figure 7 shows a comparison of the Cmax and Tmax of three nicotine liquid formulations and a reference cigarette. Due to the time limit of the washout period, the reference blood nicotine concentration (at t=-2 min and t=0 min) was higher in samples consumed later in the day of testing. The data in Figures 6-7 show corrected blood nicotine concentration values ​​(i.e., the obvious blood nicotine concentration at each time point minus the reference nicotine concentration of the same sample). Figure 8 depicts the Tmax data calculated using the corrected blood nicotine concentrations. The reference cigarette, nicotine liquid formulations containing nicotine benzoate, and nicotine liquid formulations containing nicotine malate all showed higher Cmax and lower Tmax than the nicotine liquid formulation containing free base nicotine. The better performance of nicotine liquid formulations containing nicotine benzoate and nicotine malate compared to free base nicotine is due to the superior transfer efficiency of nicotine salts from liquid to aerosol compared to free base nicotine, which allows nicotine to be delivered more efficiently to the user's lungs and / or alveoli of the user's lungs.

[0108] The content and characteristics of the tested acids in the nicotine liquid formulations provide a reasonable explanation for how the blood concentration test data confirm the lower rank of malic acid compared to benzoic acid, as described in Example 1. In plasma experiments, the nicotine malate formulation contained a 1:2 molar ratio of nicotine to malic acid, while the nicotine benzoate formulation contained a 1:1 molar ratio of nicotine to benzoic acid. As described below, malic acid is broken down at the operating temperature of the e-cigarette, so excess malic acid is required for aerosolized nicotine. Therefore, aerosols produced using malic acid are likely to contain breakdown products (which can result in an unfavorable experience for the user, thus resulting in a lower rank). For example, an unfavorable experience may include flavor, nerve reactions, and / or one or more irritations of the oral cavity, upper respiratory tract, and / or lungs.

[0109] <Example 9: Blood concentration test> Blood concentration studies were performed on 24 subjects (n=24). Eight test substances were used in this study: one reference tobacco and seven blends were delivered to users as aerosols via a cryoelectronic vaporizer (i.e., e-cigarette). The operating temperature of the e-cigarette was approximately 150°C to 250°C, or approximately 180°C to 220°C. The reference tobacco was Pall Mall (New Zealand). Seven blends were tested: 2% free base, 2% benzoate, 4% benzoate, 2% citrate, 2% malate, 2% salicylate, and 2% succinate. The seven blends were liquid formulations prepared by the protocol described in Example 1 and similar protocols below.

[0110] All subjects consumed 30-55 mg of the liquid formulation of each tested mixture. Ten puffs were performed with 30-second intervals, starting at time=0 and continuing for up to 4.5 minutes. Blood concentration studies were conducted for at least 60 minutes from the first puff, and pharmacokinetic data of nicotine in the user's plasma (Cmax, Tmax, AUC) were obtained at various times within that 60-minute period, along with the nicotine absorption rate in the first 90 seconds for each test substance.

[0111] <Example 10: Blood concentration test> Blood concentration studies were performed on 24 subjects (n=24). Eleven test substances were used in this study. One reference tobacco and 10 blends were delivered to users as aerosols via a cryoelectronic vaporizer (i.e., e-cigarette). The reference tobacco was Pall Mall (New Zealand). The operating temperature of the e-cigarette was approximately 150°C to 250°C, or approximately 180°C to 220°C. Ten blends were tested: 2% free base, 2% benzoate, 2% sorbate, 2% pyruvate, 2% laurate, 2% levulinate, 2% citrate, 2% malate, 2% salicylate, and 2% succinate. The ten blends were liquid formulations prepared by the protocol described in Example 1 and similar protocols below.

[0112] All subjects consumed 30-55 mg of the liquid formulation of each tested mixture. Ten puffs were performed with 30-second intervals, starting at time=0 and continuing for up to 4.5 minutes. Blood concentration tests occurred for at least 60 minutes from the first puff (t=0). Pharmacokinetic data of nicotine in the user's plasma (Cmax, Tmax, AUC) were obtained at various time points within that 60-minute period, along with the nicotine absorption rate of each test substance in the first 90 seconds.

[0113] <Example 11: Blood concentration test> Blood concentration studies were conducted on 24 subjects (n=24). Twenty-one test substances were used in this study: one reference tobacco and 20 blends were delivered to users as aerosols via a cryoelectronic vaporizer (i.e., e-cigarette). The reference tobacco was Pall Mall (New Zealand). The operating temperature of the e-cigarette was approximately 150°C to 250°C, or approximately 180°C to 220°C. Twenty blends were tested: 2% free base, 4% free base, 2% benzoate, 4% benzoate, 2% sorbate, 4% sorbate, 2% pyruvate, 4% pyruvate, 2% laurate, 4% laurate, 2% levulinate, 4% levulinate, 2% citrate, 4% citrate, 2% malate, 4% malate, 2% salicylate, 4% salicylate, 2% succinate, and 4% succinate. The twenty blends are liquid formulations prepared by the protocols described in Example 1 and similarly thereto below.

[0114] All subjects consumed 30-55 mg of the liquid formulation of each tested mixture. Ten puffs were performed with 30-second intervals, starting at time=0 and continuing for up to 4.5 minutes. Blood concentration tests occurred for at least 60 minutes from the first puff (t=0). Pharmacokinetic data of nicotine in the user's plasma (Cmax, Tmax, AUC) were obtained at various time points within that 60-minute period, along with the nicotine absorption rate of each test substance in the first 90 seconds.

[0115] <Example 12: Blood concentration test> Blood concentration studies were conducted on 24 subjects (n=24). Twenty-one test substances were used in this study: one reference tobacco and 20 blends were delivered to users as aerosols via a cryoelectronic vaporizer (i.e., e-cigarette). The reference tobacco was Pall Mall (New Zealand). The operating temperature of the e-cigarette was approximately 150°C to 250°C, or approximately 180°C to 220°C. Twenty blends were tested: 2% free base, 1% free base, 2% benzoate, 1% benzoate, 2% sorbate, 1% sorbate, 2% pyruvate, 1% pyruvate, 2% laurate, 1% laurate, 2% levulinate, 1% levulinate, 2% citrate, 1% citrate, 2% malate, 1% malate, 2% salicylate, 1% salicylate, 2% succinate, and 1% succinate. The twenty blends are liquid formulations prepared by the protocols described in Example 1 and similarly below.

[0116] All subjects consumed 30-55 mg of the liquid formulation of each tested mixture. Ten puffs were performed with 30-second intervals, starting at time=0 and continuing for up to 4.5 minutes. Blood concentration tests occurred for at least 60 minutes from the first puff (t=0). Pharmacokinetic data of nicotine in the user's plasma (Cmax, Tmax, AUC) were obtained at various time points within that 60-minute period, along with the nicotine absorption rate of each test substance in the first 90 seconds.

[0117] <Example 13: Aerosolized Nicotine Salt Test> The experimental system included a glass bubbler (bubbler-1), a Cambridge filter pad, and two glass bubblers (trap-1 and trap-2 connected in order) to capture any volatile substances passing through the filter pad. A cryoelectronic vaporizer (i.e., an e-cigarette) was activated by a smoking machine, connected to the inlet of bubbler-1 and to the outlet of trap-2 under the designed smoking mechanism (puffing regime). The smoking regime included: sample = 30, size = 60cc, puff duration = number of puffs every 4 seconds. The capture solvent contained 0.3% HCl in water. The nicotine liquid formulations tested were: free base nicotine, nicotine benzoates with molar ratios of nicotine to acid of 1:0.4, 1:0.7, 1:1 and 1:1.5, and nicotine malates with molar ratios of nicotine to acid of 1:0.5 and 1:2. The formulations were produced using the procedure described in Example 1. In the experimental setup, the analyte in gaseous form (i.e., vapor) was captured by a bubbler.

[0118] The procedure includes the following: * Before starting to use, measure the following parts: e-cigarette filled with nicotine liquid formulation, bubbler-1 filled with 35 ml of capture solvent, clean filter pad and pad holder, trap-1 filled with 20 ml of capture solvent, and trap-2 filled with 20 ml of capture solvent; * Connect in the following order: e-cigarette, bubbler-1, filter pad, trap-1, trap-2, and smoking machine; * Smoking was performed under the aforementioned smoking mechanism. After each puff, a breath of clean air of the same size and duration was taken; * The final step of weighing all parts of the smoking mechanism. The inlet tube material of Bubbler-1 was analyzed with 10 ml of capture solvent in 1 ml of water droplets. The total amount of solvent in Bubbler-1 after inhalation was calculated after correcting for water loss from 60 inhalations. The filter pad was cut in half, and each half was extracted with 20 ml of capture solvent for 2 hours. The pad extract was filtered through a 0.2 μm nylon syringe filter. The front half of the pad holder was analyzed with 5 ml of capture solvent. The back half of the pad holder was analyzed with 3 ml of capture solvent; * The process involved analyzing the solution using UV-Vis spectroscopy. The absorbance at 259 nm was used to calculate the nicotine concentration. The absorbance at 230 nm was used to calculate the benzoic acid concentration. The amount of malic acid was measured using a malic acid UV test kit from NZYTech.

[0119] <Results and Discussion> (Recovery of test subjects) The recovered amounts of each substance (nicotine, benzoic acid, and malic acid) were calculated as the sum of the amounts analyzed from all sites. No substances were detected in Trap-1 or Trap-2. The recovered percentage was calculated by dividing the total recovered amount by the theoretical amount produced by the e-cigarette. Table 3 shows the recovery percentages of nicotine in the nicotine free base liquid formulation, nicotine benzoate liquid formulation, and nicotine malate liquid formulation. Table 3 further shows the recovery percentages of benzoic acid in the nicotine benzoate liquid formulation and malic acid in the nicotine malate liquid formulation.

[0120] [Table 3]

[0121] The recovery percentage of malic acid was significantly lower than that of nicotine and benzoic acid, and showed considerable variability between sample replications. Malic acid was reported to decompose with heat at 150°C (a temperature lower than the typical operating temperature of e-cigarettes). The low recovery of malic acid found in aerosols is consistent with the thermal instability of malic acid. This results in a lower effective nicotine ratio to malic acid in aerosols compared to the ratio in nicotine liquid formulations. Therefore, the protonated state of nicotine is also low in aerosols, resulting in effectively less nicotine present in aerosols produced by nicotine-malate liquid formulations. The lower nicotine recovery in free base nicotine liquid formulations compared to nicotine liquid formulations may be due to sample collection or to analytical procedures that allowed small portions of gaseous nicotine to escape from the smoking system.

[0122] (Volatile nicotine in aerosols) The amount of nicotine in the aerosol released from a low-temperature volatile device, i.e., an e-cigarette, was tested by calculating the percentage of nicotine captured in Bubbler-1 compared to the total recovered nicotine. Because it is non-volatile, benzoic acid is expected to be present in the particles (i.e., droplets) in the aerosol. Since it is expected to protonate nicotine in a 1:1 molar ratio, benzoic acid is therefore used as a particle marker for nicotine. This results in nicotine present in the aerosol, and in some embodiments, in the non-gas phase of the aerosol. The amount of aerosolized nicotine was calculated by comparing the difference between the amount of benzoic acid captured in Bubbler-1 and the amount of benzoic acid in the nicotine liquid formulation.

[0123] A linear relationship was found between the amount of nicotine captured in Bubbler-1 in the nicotine liquid formulation and the molar ratio of benzoic acid to nicotine (Figure 9). At a 1:1 molar ratio of nicotine to benzoic acid, the nicotine was completely protonated, and the minimum amount of vapor recovered by Bubbler-1 was measured. Furthermore, at a 1:1.5 molar ratio of nicotine to benzoic acid, the amount of aerosolized nicotine detected did not decrease further. It is also noteworthy that a higher percentage of free base nicotine was recovered by Bubbler-1, indicating that the higher concentration of gaseous nicotine was nicotine produced when free base nicotine was used in the nicotine liquid formulation.

[0124] Theoretically, malic acid, a dibasic acid, protonates nicotine in a molar ratio of 0.5:1. However, malic acid is known to decompose at the operating temperature of e-cigarettes, resulting in low transfer efficiency from liquid formulation to aerosol. Therefore, due to the low transfer efficiency of malic acid, the effective ratio of nicotine to malic acid in the aerosol is 0.23 when using a nicotine liquid formulation containing a molar ratio of nicotine to malic acid of 1:0.5, and 0.87 when using a nicotine liquid formulation containing a molar ratio of nicotine to malic acid of 1:2. As expected, the percentage of acid captured in Publer-1 when using a nicotine liquid formulation containing a molar ratio of nicotine to malic acid of 1:0.5 is between the percentage of acid recovered when using nicotine liquid formulations containing molar ratios of nicotine to benzoic acid of 1:0.4 and 1:0.7. A nicotine liquid formulation containing a 1:2 molar ratio of nicotine to malic acid delivered an aerosol containing a 1:0.87 molar ratio of nicotine to malic acid, thereby containing more malic acid than necessary for the nicotine to be completely protonated, leaving only 14.7% of the nicotine captured in Bubbler-1 (Figure 10).

[0125] Aerosolized nicotine remaining within particles is likely to travel to the alveoli and potentially enter the user's bloodstream. Gaseous nicotine has many opportunities to be absorbed in different ratios from the gas exchange areas of the deep lungs, as it accumulates in the upper respiratory tract. Therefore, using a nicotine liquid formulation with a molar ratio of 1:1 nicotine to benzoic acid or 1:2 nicotine to malic acid, approximately the same molar amount of aerosolized nicotine in the non-gas phase is delivered to the user's lungs. This is consistent with the Tmax data described in Example 8.

[0126] <Example 14: Test of requirements for acidic functional groups> The experimental system included a glass bubbler (bubbler-1), a Cambridge filter pad, and two glass bubblers (trap-1 and trap-2 connected in order) to capture any volatile substances passing through the filter pad. A cryoelectronic vaporizer (i.e., an e-cigarette) was activated by a smoking machine, connected to the inlet of bubbler-1 and to the outlet of trap-2 under the designed smoking mechanism (puffing regime). The smoking regime included: sample = 30, size = 60cc, duration of puff = 4 seconds, number of puffs per puff. The capture solvent contained 0.3% HCl in water. The nicotine liquid formulations tested were: free base nicotine, nicotine benzoates with molar ratios of nicotine to acid of 1:0.4, 1:0.7, 1:1 and 1:1.5, and nicotine malates with molar ratios of nicotine to acid of 1:0.5 and 1:2. The formulations were produced using the procedure described in Example 1. In the experimental setup, the analyte in gaseous form (i.e., vapor) was captured by a bubbler.

[0127] The procedure includes the following: * Before starting to use, measure the following parts: e-cigarette filled with nicotine liquid formulation, bubbler-1 filled with 35 ml of capture solvent, clean filter pad and pad holder, trap-1 filled with 20 ml of capture solvent, and trap-2 filled with 20 ml of capture solvent; * Connect in the following order: e-cigarette, bubbler-1, filter pad, trap-1, trap-2, and smoking machine; * Smoking was performed under the aforementioned smoking mechanism. After each puff, a breath of clean air of the same size and duration was taken; * The final step of weighing all parts of the smoking mechanism. The inlet tube material of Bubbler-1 was analyzed with 10 ml of capture solvent in 1 ml of water droplets. The total amount of solvent in Bubbler-1 after inhalation was calculated after correcting for water loss from 60 inhalations. The filter pad was cut in half, and each half was extracted with 20 ml of capture solvent for 2 hours. The pad extract was filtered through a 0.2 μm nylon syringe filter. The front half of the pad holder was analyzed with 5 ml of capture solvent. The back half of the pad holder was analyzed with 3 ml of capture solvent; * The process involved analyzing the solution using UV-Vis spectroscopy. The absorbance at 259 nm was used to calculate the nicotine concentration. The absorbance at 230 nm was used to calculate the benzoic acid concentration. The amount of malic acid was measured using a malic acid UV test kit from NZYTech.

[0128] <Results and Discussion> The amount of nicotine in the aerosol released from a low-temperature volatile device, i.e., an e-cigarette, was tested by calculating the percentage of nicotine captured in Bubbler-1 compared to the total recovered nicotine. Because it is non-volatile, benzoic acid is expected to be present in the particles (i.e., droplets) in the aerosol. Since it is expected to protonate nicotine in a 1:1 molar ratio, benzoic acid is therefore used as a particle marker for nicotine. This results in nicotine present in the aerosol, and in some embodiments, in the non-gas phase of the aerosol. The amount of aerosolized nicotine was calculated by comparing the difference between the amount of benzoic acid captured in Bubbler-1 and the amount of benzoic acid in the nicotine liquid formulation.

[0129] A linear relationship was found between the amount of nicotine captured in Bubbler-1 in the nicotine liquid formulation and the molar ratio of benzoic acid to nicotine (Figure 9). At a 1:1 molar ratio of nicotine to benzoic acid, the nicotine was completely protonated, and the minimum amount of vapor recovered by Bubbler-1 was measured. Furthermore, at a 1:1.5 molar ratio of nicotine to benzoic acid, the amount of aerosolized nicotine detected did not decrease further. It should be further noted that a higher percentage of free base nicotine was recovered by Bubbler-1, indicating that the higher concentration of gaseous nicotine was nicotine produced when free base nicotine was used in the nicotine liquid formulation.

[0130] Benzoic acid and succinic acid have similar boiling points, 249°C for benzoic acid and 235°C for succinic acid, and both acids melt and evaporate without decomposing. Therefore, nicotine liquid formulations produced using one acid will act similarly, producing an aerosol with approximately the same molar amount of nicotine in the aerosol. Thus, when one acid is used in a nicotine liquid formulation, the same total amount of acid is recovered. When a nicotine succinate liquid formulation is used in an e-cigarette, approximately the same percentage of succinic acid is recovered compared to the percentage of benzoic acid recovered when a nicotine benzoate liquid formulation is used as described in Example 13, as described differently. Therefore, when either succinic acid or benzoic acid is used in a nicotine liquid formulation, the same percentage of nicotine is also likely captured in the bubbler-1.

[0131] Here, different molar ratios of acidic functional groups to moles of nicotine were investigated. Since succinic acid is a dibasic acid, it was expected that the same amount of acid would be captured in bubbler-1 as was captured using a 1:0.5 molar ratio of nicotine to succinic acid. Furthermore, it was expected that approximately the same amount of acid would be captured in bubbler-1 as was captured using a 1:0.5 molar ratio of nicotine to succinic acid. It was expected that the same percentage of acid would be recovered in bubbler-1 when using a 1:0.25 molar ratio of nicotine to succinic acid in a nicotine liquid formulation, as would be expected based on the amount of nicotine captured in nicotine liquid formulations with molar ratios of 1:0.4 and 1:0.7 (Figure 11). Furthermore, when using a 1:0.5 molar ratio of nicotine to succinic acid in the nicotine liquid formulation, the same percentage of acid recovered in Bubbler-1 was expected compared to using a 1:1 molar ratio of nicotine to benzoic acid.

[0132] Therefore, since succinic acid is a dibasic acid, 1 mole of succinic acid probably protonates 2 moles of nicotine, thus stabilizing 2 moles of nicotine in the aerosol. As differently described, compared to the use of benzoic acid in nicotine liquid formulations used in cryoelectronic devices (i.e., e-cigarettes), half a mole of succinic acid in nicotine liquid formulations used in cryoelectronic devices (i.e., e-cigarettes) is necessary to completely protonate nicotine and stabilize it in the aerosol. Furthermore, because the formulation contained an excess of succinic acid (a 1:2 molar ratio of succinic acid to nicotine), it is thought that an excess of succinic acid was delivered to the user, thus resulting in an unpleasant experience for the user, and therefore it was justified that succinic acid was ranked low in the satisfaction study described in Example 3. For example, the unpleasant experience includes flavor, nerve reactions and / or one or more irritations of the oral cavity, upper respiratory tract and / or lungs.

[0133] Further understanding can be gained through the intent of the numbered embodiments as follows: 1. A method for delivering nicotine to a user, comprising the step of deploying a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the e-cigarette comprises a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 0.5% (w / w) to approximately 20% (w / w) b. Molar ratio of acid to nicotine from approximately 0.25:1 to approximately 4:1; and c. A method comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 2. The method according to Embodiment 1, characterized in that the molar ratio of acidic functional groups to nicotine is about 0.25:1 to about 4:1. 3. The method according to any one of Embodiments 1-2, characterized in that the acid and nicotine form a nicotine salt. 4. The method according to Embodiments 1-7, characterized in that the nicotine preparation contains monoprotonated nicotine. 5. A method according to any one of Embodiments 1-4, characterized in that the aerosol contains monoprotonated nicotine. 6. The method according to any one of Embodiments 1-5, characterized in that the aerosol is delivered to the user's lungs. 7. The method according to Embodiment 6, characterized in that the aerosol is delivered to the alveoli in the user's lungs. 8. The method according to any one of Embodiments 1-10, characterized in that nicotine is stable in salt form in an aerosol. 9. The method according to any one of Embodiments 1-10, characterized in that nicotine is delivered in salt form in an aerosol. 10. The method according to any one of Embodiments 1-9, characterized in that the acid contains one carboxylic acid functional group. 11. The method according to any one of Embodiments 1-9, characterized in that the acid contains more than one carboxylic acid functional group. 12. The method according to any one of Embodiments 1-9, characterized in that the acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, citric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, phenylacetic acid, benzoic acid, pyruvic acid, levulinic acid, tartaric acid, lactic acid, malonic acid, succinic acid, fumaric acid, gluconic acid, sugar acid, salicylic acid, sorbic acid, masonic acid, and malic acid. 13. The method according to any one of Embodiments 1-9, characterized in that the acid comprises one or more carboxylic acids, dicarboxylic acids, and keto acids. 14. The method according to any one of Embodiments 1-9, characterized in that the acid comprises one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 15. The method according to any one of Embodiments 1-9, characterized in that the acid contains benzoic acid. 16. The method according to any one of Embodiments 1-11, characterized in that the molar ratio of acid to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 17. The method according to any one of Embodiments 1-11, characterized in that the molar ratio of acidic functional groups to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 18. The method according to any one of Embodiments 1-11, characterized in that the molar ratio of acidic functional group hydrogen to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 19. The method according to any one of Embodiments 1-11, characterized in that the molar ratio of acid to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 20. The method according to any one of Embodiments 1-11, characterized in that the molar ratio of acidic functional groups to nicotine in the aerosol is about 0.25:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1.2:1, about 1.4:1, about 1.6:1, about 1.8:1, about 2:1, about 2.2:1, about 2.4:1, about 2.6:1, about 2.8:1, about 3:1, about 3.2:1, about 3.4:1, about 3.6:1, about 3.8:1, or about 4:1. 21. The method according to any one of Embodiments 1-11, characterized in that the molar ratio of acidic functional group hydrogens to nicotine in the aerosol is about 0.25:1, about 0.3:1, about 0.4:1, about 0.5:1, about 0.6:1, about 0.7:1, about 0.8:1, about 0.9:1, about 1:1, about 1.2:1, about 1.4:1, about 1.6:1, about 1.8:1, about 2:1, about 2.2:1, about 2.4:1, about 2.6:1, about 2.8:1, about 3:1, about 3.2:1, about 3.4:1, about 3.6:1, about 3.8:1, or about 4:1. 22. Nicotine concentrations of approximately 0.5% (w / w), 1% (w / w), 2% (w / w), 3% (w / w), 4% (w / w), 5% (w / w), and 6% (w / w) are available. Approximately 7% (w / w), approximately 8% (w / w), approximately 9% (w / w), approximately 10% (w / w), approximately 11% (w / w), approximately 12% (w / w), approximately 13% (w / w), approximately 14% (w / w), approximately 15% (w / w), The method according to any one of Embodiment 1-paragraph

[0043] , characterized in that the amount is approximately 16% (w / w), approximately 17% (w / w), approximately 18% (w / w), approximately 19% (w / w), or approximately 20% (w / w). 23. Nicotine concentration from approximately 0.5% (w / w) to approximately 20% (w / w), from approximately 0.5% (w / w) to approximately 18% (w / w), from approximately 0.5% (w / w) to approximately 15% (w / w), and from approximately 0.5% (w / w) to approximately 12% (w / w). Approximately 0.5% (w / w) to approximately 10% (w / w), approximately 0.5% (w / w) to approximately 8% (w / w), approximately 0.5% (w / w) to approximately 7% (w / w), approximately 0.5% (w / w) to approximately 6% (w / w), and approximately 0.5% (w / w) to approximately 5% (w / w). From approximately 0.5% (w / w) to approximately 4% (w / w), from approximately 0.5% (w / w) to approximately 3% (w / w), Alternatively, the method according to any one of the embodiments described in paragraph

[0043] , characterized in that the amount is between approximately 0.5% (w / w) and approximately 2% (w / w). 24. Nicotine concentration from approximately 1% (w / w) to approximately 20% (w / w), from approximately 1% (w / w) to approximately 18% (w / w), from approximately 1% (w / w) to approximately 15% (w / w), from approximately 1% (w / w) to approximately 12% (w / w), from approximately 1% (w / w) to approximately 10% (w / w), from approximately 1% (w / w) to approximately 8% (w / w), and from approximately 1% (w / w) to approximately 7% (w / w). The method according to any one of the embodiments of paragraph

[0043] , characterized in that the amount is up to w / w, from about 1% (w / w) to about 6% (w / w), from about 1% (w / w) to about 5% (w / w), from about 1% (w / w) to about 4% (w / w), from about 1% (w / w) to about 3% (w / w), or from about 1% (w / w) to about 2% (w / w). 25. The method according to any one of Embodiment 1-paragraph

[0043] , characterized in that the nicotine concentration is approximately 2% (w / w) to approximately 20% (w / w), approximately 2% (w / w) to approximately 18% (w / w), approximately 2% (w / w) to approximately 15% (w / w), approximately 2% (w / w) to approximately 12% (w / w), approximately 2% (w / w) to approximately 10% (w / w), approximately 2% (w / w) to approximately 8% (w / w), approximately 2% (w / w) to approximately 7% (w / w), approximately 2% (w / w) to approximately 6% (w / w), approximately 2% (w / w) to approximately 5% (w / w), approximately 2% (w / w) to approximately 4% (w / w), or approximately 2% (w / w) to approximately 3% (w / w). 26. The method according to any one of Embodiment 1-paragraph

[0043] , characterized in that the nicotine concentration is approximately 3% (w / w) to approximately 20% (w / w), approximately 3% (w / w) to approximately 18% (w / w), approximately 3% (w / w) to approximately 15% (w / w), approximately 3% (w / w) to approximately 12% (w / w), approximately 3% (w / w) to approximately 10% (w / w), approximately 3% (w / w) to approximately 8% (w / w), approximately 3% (w / w) to approximately 7% (w / w), approximately 3% (w / w) to approximately 6% (w / w), approximately 3% (w / w) to approximately 5% (w / w), or approximately 3% (w / w) to approximately 4% (w / w). 27. The method according to any one of the embodiments of paragraph

[0043] , characterized in that the nicotine concentration is approximately 4% (w / w) to approximately 20% (w / w), approximately 4% (w / w) to approximately 18% (w / w), approximately 4% (w / w) to approximately 15% (w / w), approximately 4% (w / w) to approximately 12% (w / w), approximately 4% (w / w) to approximately 10% (w / w), approximately 4% (w / w) to approximately 8% (w / w), approximately 4% (w / w) to approximately 7% (w / w), approximately 4% (w / w) to approximately 6% (w / w), or approximately 4% (w / w) to approximately 5% (w / w). 28. The method according to any one of the embodiments of paragraph

[0043] , characterized in that the nicotine concentration is approximately 5% (w / w) to approximately 20% (w / w), approximately 5% (w / w) to approximately 18% (w / w), approximately 5% (w / w) to approximately 15% (w / w), approximately 5% (w / w) to approximately 12% (w / w), approximately 5% (w / w) to approximately 10% (w / w), approximately 5% (w / w) to approximately 8% (w / w), approximately 5% (w / w) to approximately 7% (w / w), or approximately 5% (w / w) to approximately 6% (w / w). 29. The method according to any one of Embodiment 1-paragraph

[0043] , characterized in that the nicotine concentration is approximately 6% (w / w) to approximately 20% (w / w), approximately 6% (w / w) to approximately 18% (w / w), approximately 6% (w / w) to approximately 15% (w / w), approximately 6% (w / w) to approximately 12% (w / w), approximately 6% (w / w) to approximately 10% (w / w), approximately 6% (w / w) to approximately 8% (w / w), or approximately 6% (w / w) to approximately 7% (w / w). 30. The method according to any one of Embodiments 1-

[0043] , characterized in that the nicotine concentration is approximately 2% (w / w) to approximately 6% (w / w). 31. The method according to any one of Embodiments 1-

[0043] , characterized in that the nicotine concentration is approximately 5% (w / w). 32. The method according to any one of Embodiments 1-

[0061] , characterized in that the molar concentration of nicotine in the aerosol is approximately the same as the molar concentration of acid in the aerosol. 33. The method according to any one of Embodiments 1-32, characterized in that the aerosol contains approximately 50% of the nicotine in the formulation, approximately 60% of the nicotine in the formulation, approximately 70% of the nicotine in the formulation, approximately 75% of the nicotine in the formulation, approximately 80% of the nicotine in the formulation, approximately 85% of the nicotine in the formulation, approximately 90% of the nicotine in the formulation, approximately 95% of the nicotine in the formulation, or approximately 99% of the nicotine in the formulation. 34. Aerosols range from approximately 0.1 microns to approximately 5 microns, approximately 0.1 microns to approximately 4.5 microns, approximately 0.1 microns to approximately 4 microns, approximately 0.1 microns to approximately 3.5 microns, approximately 0.1 microns to approximately 3 microns, approximately 0.1 microns to approximately 2.5 microns, approximately 0.1 microns to approximately 2 microns, approximately 0.1 microns to approximately 1.5 microns, approximately 0.1 microns to approximately 1 micron, approximately 0.1 microns to approximately 0.9 microns, and approximately 0.1 microns to approximately 0.8 microns. The method according to any one of Embodiments 1-33, characterized by comprising a condensate having particle sizes up to a micron, from about 0.1 microns to about 0.7 microns, from about 0.1 microns to about 0.6 microns, from about 0.1 microns to about 0.5 microns, from about 0.1 microns to about 0.4 microns, from about 0.1 microns to about 0.4 microns, from about 0.1 microns to about 0.3 microns, or from about 0.3 to about 0.2 microns, or from about 0.3 microns to about 0.4 microns. 35. The method according to Embodiments 1-34, characterized in that the aerosol contains a condensate of nicotine salt. 36. The method according to Embodiments 1-34, characterized in that the aerosol comprises a condensate containing one or more of a carrier, a nicotine salt, free base nicotine, and a free acid. 37. The method according to Embodiments 1-9, characterized in that the acid does not decompose at room temperature and does not decompose at the operating temperature of the e-cigarette. 38. The method according to any one of embodiments 1 to 37, characterized in that the operating temperature is between 150°C and 250°C. 39. The method according to any one of embodiments 1 to 37, characterized in that the operating temperature is between 180°C and 220°C. 40. The method according to any one of Embodiments 1-37, characterized in that the operating temperature is approximately 200°C. 41. The method according to any one of Embodiments 1-40, characterized in that the acid is stable at or below the operating temperature. 42. The method according to any one of Embodiments 1-40, characterized in that the acid does not decompose at or below the operating temperature. 43. The method according to any one of Embodiments 1-40, characterized in that the acid does not oxidize at or below the operating temperature. 44. The method according to any one of Embodiments 1-43, characterized in that the formulation is nontoxic to e-cigarette users. 45. The method according to any one of Embodiments 1 to 44, characterized in that the formulation does not corrode the e-cigarette. 46. ​​The method according to any one of Embodiments 1 to 45, characterized in that the formulation contains a flavoring agent. 47. The method according to any one of Embodiments 1-46, characterized in that inhalation of an aerosol for 5 minutes at a rate of one inhalation every 30 seconds results in a nicotine plasma Tmax of approximately 1 to 8 minutes. 48. Nicotine COMTmax is approximately 1 minute to 7 minutes, approximately 1 minute to 6 minutes, approximately 1 minute to 5 minutes, approximately 1 minute to 4 minutes, approximately 1 minute to 3 minutes, approximately 1 minute to 2 minutes, approximately 2 minutes to 8 minutes, approximately 2 minutes to 7 minutes, approximately 2 minutes to 6 minutes, approximately 2 minutes to 5 minutes, approximately 2 minutes to 4 minutes, approximately 2 minutes to 3 minutes, approximately 3 minutes to 8 minutes, approximately 3 minutes to 7 minutes, approximately 3 minutes to 6 minutes, approximately 3 minutes to 5 minutes, approximately 3 minutes to 4 minutes, approximately 4 minutes The method of Embodiment 47, characterized in that the time is approximately 7 minutes, 4 minutes to 6 minutes, 4 minutes to 5 minutes, 5 minutes to 8 minutes, 5 minutes to 7 minutes, 5 minutes to 6 minutes, 6 minutes to 8 minutes, 6 minutes to 7 minutes, 7 minutes to 8 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, less than 5 minutes, less than 4 minutes, less than 3 minutes, less than 2 minutes, less than 1 minute, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, or 1 minute. 49. A method from any one of Embodiments 1 to 46, characterized in that inhalation of an aerosol at a rate of one inhalation every 30 seconds for approximately 5 minutes results in a nicotine plasma Tmax of approximately 2 to 8 minutes. 50. Nicotine COMTmax is approximately 2 to 8 minutes, approximately 2 to 7 minutes, approximately 2 to 6 minutes, approximately 2 to 5 minutes, approximately 2 to 4 minutes, approximately 2 to 3 minutes, approximately 3 to 8 minutes, approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 to 7 minutes, approximately 4 to 6 minutes, approximately 4 to 5 minutes, approximately The method of Embodiment 49, characterized in that the duration is 5 minutes to approximately 8 minutes, approximately 5 minutes to approximately 7 minutes, approximately 5 minutes to approximately 6 minutes, approximately 6 minutes to approximately 8 minutes, approximately 6 minutes to approximately 7 minutes, approximately 7 minutes to approximately 8 minutes, less than approximately 8 minutes, less than approximately 7 minutes, less than approximately 6 minutes, less than approximately 5 minutes, less than approximately 4 minutes, less than approximately 3 minutes, less than approximately 2 minutes, less than approximately 1 minute, approximately 8 minutes, approximately 7 minutes, approximately 6 minutes, approximately 5 minutes, approximately 4 minutes, approximately 3 minutes, or approximately 2 minutes. 51. A method from any one of Embodiments 1-46, characterized in that inhalation of an aerosol at a rate of one inhalation every 30 seconds for approximately 5 minutes results in a nicotine plasma Tmax of approximately 3 to 8 minutes. 52. The method of Embodiment 51, characterized in that the nicotine COMTmax is approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 to 8 minutes, approximately 4 to 7 minutes, approximately 4 to 6 minutes, approximately 4 to 5 minutes, approximately 5 to 8 minutes, approximately 5 to 7 minutes, approximately 5 to 6 minutes, approximately 6 to 8 minutes, approximately 6 to 7 minutes, approximately 7 to 8 minutes, less than approximately 8 minutes, less than approximately 7 minutes, less than approximately 6 minutes, less than approximately 5 minutes, less than approximately 4 minutes, approximately 8 minutes, approximately 7 minutes, approximately 6 minutes, approximately 5 minutes, approximately 4 minutes, or approximately 3 minutes. 53. The method according to any one of Embodiments 1-46, characterized in that Tmax is less than approximately 8 minutes. 54. The method according to any one of embodiments 47-53, characterized in that Tmax is determined based on at least three independent datasets. 55. The method according to embodiments 47-53, characterized in that Tmax is the range of at least three independent datasets. 56. The method according to embodiments 47-53, characterized in that Tmax is the mean ± standard deviation of at least three independent datasets. 57. The method according to any one of Embodiments 1 to 56, characterized in that the liquid carrier comprises glycerin, propylene glycol, trimethylene glycol, water, ethanol, or a combination thereof. 58. A method according to any one of Embodiments 1 to 56, characterized in that the liquid carrier comprises propylene glycol and vegetable glycerin. 59. Any one of Embodiments 1-56, characterized in that the liquid carrier contains 20% to 50% propylene glycol and 80% to 50% vegetable glycerin. 60. Any one of Embodiments 1-56, characterized in that the liquid carrier comprises 30% propylene glycol and 70% vegetable glycerin. 61. The method according to any one of Embodiments 1-17, characterized in that the formulation further comprises one or more additional acids. 62. The method according to Embodiment 21, characterized in that one or more additional acids include one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 63. The method according to Embodiment 21, characterized in that one or more additional acids include benzoic acid. 64. The method according to any one of embodiments 21-63, characterized in that one or more additional acids form one or more additional nicotine salts. 65. A method for delivering nicotine to a user, comprising the step of deploying a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the e-cigarette comprises a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 0.5% (w / w) to approximately 20% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is approximately 0.25:1 to approximately 4:1; and c. A method comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 66. A method for delivering nicotine to a user, comprising the step of deploying a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the e-cigarette comprises a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is approximately 0.25:1 to approximately 4:1; and, c. A method comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 67. A method for delivering nicotine to a user, comprising the step of deploying a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the e-cigarette comprises a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is about 1:1 to about 2:1; and c. A method comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 68. A method for delivering nicotine to a user, comprising the step of deploying a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the e-cigarette comprises a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. The molar ratio of benzoic acid to nicotine is approximately 1:1; and c. A method comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 69. A preparation for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the preparation is: a. Nicotine content ranging from approximately 0.5% (w / w) to approximately 20% (w / w); b. The molar ratio of acid to nicotine is approximately 0.25:1 to approximately 4:1; and c. A method comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 70. The formulation according to Embodiment 69, characterized in that the molar ratio of acidic functional groups to nicotine is from about 1:1 to about 4:1. 71. A formulation according to any one of embodiments 69-70, characterized in that an acid and nicotine form a nicotine salt. 72. Formulations of embodiments 69-71, characterized by containing monoprotonated nicotine. 73. A formulation according to any one of embodiments 69-72, characterized in that the aerosol contains monoprotonated nicotine. 74. A formulation according to any one of embodiments 69-73, characterized in that the aerosol is delivered to the user's lungs. 75. The formulation according to Embodiment 74, characterized in that the aerosol is delivered to the alveoli in the user's lungs. 76. A formulation according to any one of embodiments 69-75, characterized in that nicotine is stable in salt form in an aerosol. 77. A formulation according to any one of embodiments 69-75, characterized in that nicotine is delivered in the form of a salt in an aerosol. 78. The formulation according to any one of embodiments 69-77, characterized in that the acid contains one carboxylic acid functional group. 79. The formulation according to any one of embodiments 69-77, characterized in that the acid contains one or more carboxylic acid functional groups. 80. A formulation according to any one of Embodiments 69-77, characterized in that the acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, citric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, phenylacetic acid, benzoic acid, pyruvic acid, levulinic acid, tartaric acid, lactic acid, malonic acid, succinic acid, fumaric acid, gluconic acid, sugar acid, salicylic acid, sorbic acid, masonic acid, or malic acid. 81. A formulation according to any one of embodiments 69-77, characterized in that the acid comprises one or more carboxylic acids, dicarboxylic acids, and keto acids. 82. A formulation according to any one of Embodiments 69-77, characterized in that the acid comprises one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 83. A formulation according to any one of Embodiments 69-77, characterized in that the acid contains nicotine benzoate. 84. A formulation according to any one of Embodiments 69-83, characterized in that the molar ratio of acid to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 85. A formulation according to any one of Embodiments 69-83, characterized in that the molar ratio of acidic functional groups to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 86. A formulation according to any one of Embodiments 69-83, characterized in that the molar ratio of acidic functional group hydrogen to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 87. A formulation according to any one of Embodiments 69-83, characterized in that the molar ratio of acid to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 88. A formulation according to any one of Embodiments 69-83, characterized in that the molar ratio of acidic functional groups to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 89. A formulation according to any one of Embodiments 69-83, characterized in that the molar ratio of acidic functional group hydrogen to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 90. Nicotine concentration from approximately 0.5% (w / w) to approximately 20% (w / w), from approximately 0.5% (w / w) to approximately 18% (w / w), from approximately 0.5% (w / w) to approximately 15% (w / w), and from approximately 0.5% (w / w) to approximately 12% (w / w). From approximately 0.5% (w / w) to approximately 10% (w / w), from approximately 0.5% (w / w) to approximately 8% (w / w), from approximately 0.5% (w / w) to approximately 7% (w / w), from approximately 0.5% (w / w) to approximately 6% (w / w), from approximately 0.5% (w / w) to approximately 5% (w / w), From approximately 0.5% (w / w) to approximately 4% (w / w), from approximately 0.5% (w / w) to approximately 3% (w / w), Alternatively, the formulation according to any one of Embodiments 69-89, characterized in that the concentration is approximately 0.5% (w / w) to approximately 2% (w / w). 91. Nicotine concentrations of approximately 0.5% (w / w), 1% (w / w), 2% (w / w), 3% (w / w), 4% (w / w), 5% (w / w), 6% (w / w), and 7% (w / w), A formulation according to any one of Embodiments 69-89, characterized in that the content is approximately 8% (w / w), approximately 9% (w / w), approximately 10% (w / w), approximately 11% (w / w), approximately 12% (w / w), approximately 13% (w / w), approximately 14% (w / w), approximately 15% (w / w), approximately 16% (w / w), approximately 17% (w / w), approximately 18% (w / w), approximately 19% (w / w), or approximately 20% (w / w). 92. Nicotine concentration from approximately 1% (w / w) to approximately 20% (w / w), from approximately 1% (w / w) to approximately 18% (w / w), from approximately 1% (w / w) to approximately 15% (w / w), from approximately 1% (w / w) to approximately 12% (w / w), from approximately 1% (w / w) to approximately 10% (w / w), from approximately 1% (w / w) to approximately 8% (w / w), from approximately 1% (w / w) to approximately 7% (w / w), from approximately 1% (w / w) to approximately 6% (w / w), and from approximately 1% (w / w) to approximately 5% (w / w). From approximately 1% (w / w) to approximately 4% (w / w), from approximately 1% (w / w) to approximately 3% (w / w), Alternatively, the formulation according to any one of Embodiments 69-89, characterized in that the concentration is approximately 1% (w / w) to approximately 2% (w / w). 93. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is approximately 2% (w / w) to approximately 20% (w / w), approximately 2% (w / w) to approximately 18% (w / w), approximately 2% (w / w) to approximately 15% (w / w), approximately 2% (w / w) to approximately 12% (w / w), approximately 2% (w / w) to approximately 10% (w / w), approximately 2% (w / w) to approximately 8% (w / w), approximately 2% (w / w) to approximately 7% (w / w), approximately 2% (w / w) to approximately 6% (w / w), approximately 2% (w / w) to approximately 5% (w / w), approximately 2% (w / w) to approximately 4% (w / w), or approximately 2% (w / w) to approximately 3% (w / w). 94. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is approximately 3% (w / w) to approximately 20% (w / w), approximately 3% (w / w) to approximately 18% (w / w), approximately 3% (w / w) to approximately 15% (w / w), approximately 3% (w / w) to approximately 12% (w / w), approximately 3% (w / w) to approximately 10% (w / w), approximately 3% (w / w) to approximately 8% (w / w), approximately 3% (w / w) to approximately 7% (w / w), approximately 3% (w / w) to approximately 6% (w / w), approximately 3% (w / w) to approximately 5% (w / w), or approximately 3% (w / w) to approximately 4% (w / w). 95. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is approximately 4% (w / w) to approximately 20% (w / w), approximately 4% (w / w) to approximately 18% (w / w), approximately 4% (w / w) to approximately 15% (w / w), approximately 4% (w / w) to approximately 12% (w / w), approximately 4% (w / w) to approximately 10% (w / w), approximately 4% (w / w) to approximately 8% (w / w), approximately 4% (w / w) to approximately 7% (w / w), approximately 4% (w / w) to approximately 6% (w / w), or approximately 4% (w / w) to approximately 5% (w / w). 96. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is approximately 5% (w / w) to approximately 20% (w / w), approximately 5% (w / w) to approximately 18% (w / w), approximately 5% (w / w) to approximately 15% (w / w), approximately 5% (w / w) to approximately 12% (w / w), approximately 5% (w / w) to approximately 10% (w / w), approximately 5% (w / w) to approximately 8% (w / w), approximately 5% (w / w) to approximately 7% (w / w), or approximately 5% (w / w) to approximately 6% (w / w). 97. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is 6% (w / w) to approximately 20% (w / w), approximately 6% (w / w) to approximately 18% (w / w), approximately 6% (w / w) to approximately 15% (w / w), approximately 6% (w / w) to approximately 12% (w / w), approximately 6% (w / w) to approximately 10% (w / w), approximately 6% (w / w) to approximately 8% (w / w), or approximately 6% (w / w) to approximately 7% (w / w). 98. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is between approximately 2% (w / w) and approximately 6% (w / w). 99. A formulation according to any one of Embodiments 69-89, characterized in that the nicotine concentration is approximately 5% (w / w). 100. A formulation according to any one of Embodiments 69-99, characterized in that the molar concentration of nicotine in the aerosol is approximately the same as the molar concentration of acid in the aerosol. 101. A formulation according to any one of Embodiments 69-100, characterized in that the aerosol contains approximately 50% of the nicotine in the formulation, approximately 60% of the nicotine in the formulation, approximately 70% of the nicotine in the formulation, approximately 75% of the nicotine in the formulation, approximately 80% of the nicotine in the formulation, approximately 85% of the nicotine in the formulation, approximately 90% of the nicotine in the formulation, approximately 95% of the nicotine in the formulation, or approximately 99% of the nicotine in the formulation. 102. Aerosols range from approximately 0.1 microns to approximately 5 microns, approximately 0.1 microns to approximately 4.5 microns, approximately 0.1 microns to approximately 4 microns, approximately 0.1 microns to approximately 3.5 microns, approximately 0.1 microns to approximately 3 microns, approximately 0.1 microns to approximately 2.5 microns, approximately 0.1 microns to approximately 2 microns, approximately 0.1 microns to approximately 1.5 microns, approximately 0.1 microns to approximately 1 micron, approximately 0.1 microns to approximately 0.9 microns, and approximately 0 A formulation according to any one of Embodiments 69-101, characterized in that it contains a condensate in particle sizes ranging from 0.1 microns to approximately 0.8 microns, approximately 0.1 microns to approximately 0.7 microns, approximately 0.1 microns to approximately 0.6 microns, approximately 0.1 microns to approximately 0.5 microns, approximately 0.1 microns to approximately 0.4 microns, approximately 0.1 microns to approximately 0.3 microns, approximately 0.1 microns to approximately 0.2 microns, or approximately 0.3 to approximately 0.4 microns. 103. A formulation according to any one of Embodiments 69-102, characterized in that the aerosol contains a condensate of a nicotine salt. 104. A formulation according to any one of Embodiments 69-102, characterized in that the aerosol comprises a condensate containing one or more of a carrier, a nicotine salt, free base nicotine, and a free acid. 105. A formulation according to any one of embodiments 69-104, characterized in that the acid does not decompose at room temperature and does not decompose at the operating temperature of an e-cigarette. 106. A formulation according to any one of embodiments 69-105, characterized in that the operating temperature of the e-cigarette is between 150°C and 250°C. 107. A formulation according to any one of embodiments 69-105, characterized in that the operating temperature of the e-cigarette is between 180°C and 220°C. 108. A formulation according to any one of embodiments 69-105, characterized in that the operating temperature of the e-cigarette is approximately 200°C. 109. The formulation according to any one of embodiments 69-108, characterized in that the acid is stable at the operating temperature of the e-cigarette, or at about 200°C and below. 110. The formulation according to any one of embodiments 69-108, characterized in that the acid does not decompose at the operating temperature of the e-cigarette, or at approximately 200°C, or below. 111. The formulation according to any one of Embodiments 69-108, characterized in that the acid does not oxidize at the operating temperature of the e-cigarette, or at approximately 200°C, or below. 112. The formulation according to any one of embodiments 69-108, characterized in that the formulation is nontoxic to users of e-cigarettes. 113. The formulation according to any one of embodiments 69-112, characterized in that the formulation does not corrode electronic cigarettes. 114. The formulation according to any one of embodiments 69-113, characterized in that the formulation contains a flavoring agent. 115. A formulation according to any one of Embodiments 69-114, characterized in that inhalation of an aerosol at a rate of one inhalation every 30 seconds for 5 minutes results in a nicotine plasma Tmax of approximately 1 to 8 minutes. 116. Nicotine plasma Tmax is approximately 1 minute to 7 minutes, approximately 1 minute to 6 minutes, approximately 1 minute to 5 minutes, approximately 1 minute to 4 minutes, approximately 1 minute to 3 minutes, approximately 1 minute to 2 minutes, approximately 2 minutes to 8 minutes, approximately 2 minutes to 7 minutes, approximately 2 minutes to 6 minutes, approximately 2 minutes to 5 minutes, approximately 2 minutes to 4 minutes, approximately 2 minutes to 3 minutes, approximately 3 minutes to 8 minutes, approximately 3 minutes to 7 minutes, approximately 3 minutes to 6 minutes, approximately 3 minutes to 5 minutes, approximately 3 minutes to 4 minutes, approximately 4 minutes A formulation of Embodiment 115, characterized in that the time is approximately 7 minutes, 4 minutes to 6 minutes, 4 minutes to 5 minutes, 5 minutes to 8 minutes, 5 minutes to 7 minutes, 5 minutes to 6 minutes, 6 minutes to 8 minutes, 6 minutes to 7 minutes, 7 minutes to 8 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, less than 5 minutes, less than 4 minutes, less than 3 minutes, less than 2 minutes, less than 1 minute, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, or 1 minute. 117. Any one formulation of Embodiments 69-114, characterized in that inhalation of an aerosol at a rate of one inhalation every 30 seconds for approximately 5 minutes results in a nicotine plasma Tmax of approximately 2 to 8 minutes. 118. Nicotine COMTmax is approximately 2 to 8 minutes, approximately 2 to 7 minutes, approximately 2 to 6 minutes, approximately 2 to 5 minutes, approximately 2 to 4 minutes, approximately 2 to 3 minutes, approximately 3 to 8 minutes, approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 to 7 minutes, approximately 4 to 6 minutes, approximately 4 to 5 minutes, approximately 5 The formulation according to Embodiment 117, characterized in that the time ranges from 1 minute to approximately 8 minutes, from approximately 5 minutes to approximately 7 minutes, from approximately 5 minutes to approximately 6 minutes, from approximately 6 minutes to approximately 8 minutes, from approximately 6 minutes to approximately 7 minutes, from approximately 7 minutes to approximately 8 minutes, less than approximately 8 minutes, less than approximately 7 minutes, less than approximately 6 minutes, less than approximately 5 minutes, less than approximately 4 minutes, less than approximately 3 minutes, less than approximately 2 minutes, less than approximately 1 minute, approximately 8 minutes, approximately 7 minutes, approximately 6 minutes, approximately 5 minutes, approximately 4 minutes, approximately 3 minutes, or approximately 2 minutes. 119. A formulation according to any one of embodiments 69-114, characterized in that inhalation of an aerosol at a rate of one inhalation every 30 seconds for approximately 5 minutes results in a nicotine plasma Tmax of approximately 3 to 8 minutes. 120. The formulation according to Embodiment 119, characterized in that the nicotine plasma Tmax is approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 to 8 minutes, approximately 4 to 7 minutes, approximately 4 to 6 minutes, approximately 4 to 5 minutes, approximately 5 to 8 minutes, approximately 5 to 7 minutes, approximately 5 to 6 minutes, approximately 6 to 8 minutes, approximately 6 to 7 minutes, approximately 7 to 8 minutes, less than approximately 8 minutes, less than approximately 7 minutes, less than approximately 6 minutes, less than approximately 5 minutes, less than approximately 4 minutes, approximately 8 minutes, approximately 7 minutes, approximately 6 minutes, approximately 5 minutes, approximately 4 minutes, or approximately 3 minutes. 121. A formulation according to any one of embodiments 69-114, characterized in that Tmax is less than approximately 8 minutes. 122. The formulation according to any one of embodiments 115-121, characterized in that Tmax is determined based on at least three independent datasets. 123. The formulation according to Embodiments 115-121, characterized in that Tmax is within the range of at least three independent datasets. 124. The formulation according to Embodiments 115-121, characterized in that Tmax is the mean ± standard deviation of at least three independent datasets. 125. The formulation according to any one of Embodiments 69-124, characterized in that the liquid carrier comprises glycerin, propylene glycol, trimethylene glycol, water, ethanol, or a combination thereof. 126. The formulation according to any one of Embodiments 69-124, characterized in that the liquid carrier contains propylene glycol and vegetable glycerin. 127. The formulation according to any one of Embodiments 69-124, characterized in that the liquid carrier contains 20% to 50% propylene glycol and 80% to 50% vegetable glycerin. 128. The formulation according to any one of Embodiments 69-114, characterized in that the liquid carrier contains 30% propylene glycol and 70% vegetable glycerin. 129. The formulation according to any one of embodiments 69-128, characterized in that the formulation further comprises one or more additional acids. 130. The formulation according to Embodiment 129, characterized in that one or more additional acids comprise one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 131. The formulation according to Embodiment 129, characterized in that one or more additional acids include benzoic acid. 132. A formulation according to any one of the embodiments 129-131, characterized in that one or more additional acids form one or more additional nicotine salts. 133. A preparation for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the preparation is: a. Nicotine content ranging from approximately 0.5% (w / w) to approximately 20% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is approximately 0.25:1 to approximately 4:1; and c. A formulation comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 134. A preparation for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is approximately 0.25:1 to approximately 4:1; and c. A formulation comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 135. A preparation for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is about 1:1 to about 2:1; and c. A formulation comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 136. A preparation for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. The molar ratio of benzoic acid to nicotine is approximately 1:1; and c. A formulation comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 137. A cartridge for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the cartridge includes a fluid compartment formed to be in fluid communication with a heating element, the fluid compartment contains a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 0.5% (w / w) to approximately 20% (w / w); b. The molar ratio of acid to nicotine is approximately 0.25:1 to approximately 4:1; and c. A cartridge comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 138. The cartridge according to Embodiment 137, characterized in that the molar ratio of acidic functional groups to nicotine is from about 1:1 to about 4:1. 139. A cartridge according to any one of embodiments 137, 138, characterized in that an acid and nicotine form a nicotine salt. 140. The cartridge according to embodiments 137-139, characterized by containing monoprotonated nicotine. 141. A cartridge according to any one of embodiments 137-140, characterized in that the aerosol contains monoprotonated nicotine. 142. A cartridge according to any one of embodiments 137-141, characterized in that an aerosol is delivered to the user's lungs. 143. The cartridge according to Embodiment 142, characterized in that the aerosol is delivered to the alveoli in the user's lungs. 144. A cartridge according to any one of Embodiments 137-143, characterized in that nicotine is stable in salt form in an aerosol. 145. A cartridge according to any one of embodiments 137-143, characterized in that nicotine is delivered in the form of a salt in an aerosol. 146. A cartridge according to any one of embodiments 137-145, characterized in that the acid contains one carboxylic acid functional group. 147. A cartridge according to any one of embodiments 137-143, characterized in that the acid contains one or more carboxylic acid functional groups. 148. A cartridge according to any one of Embodiments 137-145, characterized in that the acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, citric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, phenylacetic acid, benzoic acid, pyruvic acid, levulinic acid, tartaric acid, lactic acid, malonic acid, succinic acid, fumaric acid, gluconic acid, sugar acid, salicylic acid, sorbic acid, masonic acid, or malic acid. 149. A cartridge according to any one of embodiments 137-145, characterized in that the acid comprises one or more carboxylic acids, dicarboxylic acids, and keto acids. 150. A cartridge according to any one of embodiments 137-145, characterized in that the acid comprises one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 151. A cartridge according to any one of embodiments 137-145, characterized in that the acid contains nicotine benzoate. 152. A cartridge according to any one of Embodiments 137-151, characterized in that the molar ratio of acid to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 153. A cartridge according to any one of Embodiments 137-151, characterized in that the molar ratio of acidic functional groups to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 154. A cartridge according to any one of Embodiments 137-151, characterized in that the molar ratio of acidic functional group hydrogen to nicotine in the formulation is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 155. A cartridge according to any one of Embodiments 137-151, characterized in that the molar ratio of acid to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 156. A cartridge according to any one of Embodiments 137-151, characterized in that the molar ratio of acidic functional groups to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 157. A cartridge according to any one of Embodiments 137-151, characterized in that the molar ratio of acidic functional group hydrogens to nicotine in the aerosol is approximately 0.25:1, approximately 0.3:1, approximately 0.4:1, approximately 0.5:1, approximately 0.6:1, approximately 0.7:1, approximately 0.8:1, approximately 0.9:1, approximately 1:1, approximately 1.2:1, approximately 1.4:1, approximately 1.6:1, approximately 1.8:1, approximately 2:1, approximately 2.2:1, approximately 2.4:1, approximately 2.6:1, approximately 2.8:1, approximately 3:1, approximately 3.2:1, approximately 3.4:1, approximately 3.6:1, approximately 3.8:1, or approximately 4:1. 158. Nicotine concentrations of approximately 0.5% (w / w), 1% (w / w), 2% (w / w), 3% (w / w), 4% (w / w), 5% (w / w), 6% (w / w), and 7% (w / w), A cartridge according to any one of Embodiments 137-157, characterized in that the content is approximately 8% (w / w), approximately 9% (w / w), approximately 10% (w / w), approximately 11% (w / w), approximately 12% (w / w), approximately 13% (w / w), approximately 14% (w / w), approximately 15% (w / w), approximately 16% (w / w), approximately 17% (w / w), approximately 18% (w / w), approximately 19% (w / w), or approximately 20% (w / w). 159. Nicotine concentration from approximately 0.5% (w / w) to approximately 20% (w / w), from approximately 0.5% (w / w) to approximately 18% (w / w), from approximately 0.5% (w / w) to approximately 15% (w / w), from approximately 0.5% (w / w) to approximately 12% (w / w), from approximately 0.5% (w / w) to approximately 10% (w / w), from approximately 0.5% (w / w) to approximately 8% (w / w), and from approximately 0.5% (w / w) to approximately 7%. A cartridge according to any one of Embodiments 137-157, characterized in that the content is up to (w / w), from approximately 0.5%(w / w) to approximately 6%(w / w), from approximately 0.5%(w / w) to approximately 5%(w / w), from approximately 0.5%(w / w) to approximately 4%(w / w), from approximately 0.5%(w / w) to approximately 3%(w / w), or from approximately 0.5%(w / w) to approximately 2%(w / w). 160. Nicotine concentration from approximately 1% (w / w) to approximately 20% (w / w), from approximately 1% (w / w) to approximately 18% (w / w), from approximately 1% (w / w) to approximately 15% (w / w), from approximately 1% (w / w) to approximately 12% (w / w), from approximately 1% (w / w) to approximately 10% (w / w), from approximately 1% (w / w) to approximately 8% (w / w), (approximately 1% (w / w) to approximately 7% (w / w) A cartridge according to any one of Embodiments 137-157, characterized in that the wattage is up to approximately 1% (w / w) to approximately 6% (w / w), approximately 1% (w / w) to approximately 5% (w / w), approximately 1% (w / w) to approximately 4% (w / w), approximately 1% (w / w) to approximately 3% (w / w), or approximately 1% (w / w) to approximately 2% (w / w). 161. A formulation according to any one of Embodiments 137-157, characterized in that the nicotine concentration is approximately 2% (w / w) to approximately 20% (w / w), approximately 2% (w / w) to approximately 18% (w / w), approximately 2% (w / w) to approximately 15% (w / w), approximately 2% (w / w) to approximately 12% (w / w), approximately 2% (w / w) to approximately 10% (w / w), approximately 2% (w / w) to approximately 8% (w / w), approximately 2% (w / w) to approximately 7% (w / w), approximately 2% (w / w) to approximately 6% (w / w), approximately 2% (w / w) to approximately 5% (w / w), approximately 2% (w / w) to approximately 4% (w / w), or approximately 2% (w / w) to approximately 3% (w / w). 162. A cartridge according to any one of Embodiments 137-157, characterized in that the nicotine concentration is approximately 3% (w / w) to approximately 20% (w / w), approximately 3% (w / w) to approximately 18% (w / w), approximately 3% (w / w) to approximately 15% (w / w), approximately 3% (w / w) to approximately 12% (w / w), approximately 3% (w / w) to approximately 10% (w / w), approximately 3% (w / w) to approximately 8% (w / w), approximately 3% (w / w) to approximately 7% (w / w), approximately 3% (w / w) to approximately 6% (w / w), approximately 3% (w / w) to approximately 5% (w / w), or approximately 3% (w / w) to approximately 4% (w / w). 163. A cartridge according to any one of Embodiments 137-157, characterized in that the nicotine concentration is approximately 4% (w / w) to approximately 20% (w / w), approximately 4% (w / w) to approximately 18% (w / w), approximately 4% (w / w) to approximately 15% (w / w), approximately 4% (w / w) to approximately 12% (w / w), approximately 4% (w / w) to approximately 10% (w / w), approximately 4% (w / w) to approximately 8% (w / w), approximately 4% (w / w) to approximately 7% (w / w), approximately 4% (w / w) to approximately 6% (w / w), or approximately 4% (w / w) to approximately 5% (w / w). 164. A cartridge according to any one of Embodiments 137-157, characterized in that the nicotine concentration is approximately 5% (w / w) to approximately 20% (w / w), approximately 5% (w / w) to approximately 18% (w / w), approximately 5% (w / w) to approximately 15% (w / w), approximately 5% (w / w) to approximately 12% (w / w), approximately 5% (w / w) to approximately 10% (w / w), approximately 5% (w / w) to approximately 8% (w / w), approximately 5% (w / w) to approximately 7% (w / w), or approximately 5% (w / w) to approximately 6% (w / w). 165. A cartridge according to any one of Embodiments 137-157, characterized in that the nicotine concentration is 6% (w / w) to approximately 20% (w / w), approximately 6% (w / w) to approximately 18% (w / w), approximately 6% (w / w) to approximately 15% (w / w), approximately 6% (w / w) to approximately 12% (w / w), approximately 6% (w / w) to approximately 10% (w / w), approximately 6% (w / w) to approximately 8% (w / w), or approximately 6% (w / w) to approximately 7% (w / w). 166. One cartridge from any of embodiments 137-157, characterized in that the nicotine concentration is between approximately 2% (w / w) and approximately 6% (w / w). 167. A cartridge according to any one of embodiments 137-157, characterized in that the nicotine concentration is approximately 5% (w / w). 168. A cartridge according to any one of embodiments 137-157, characterized in that the molar concentration of nicotine in the aerosol is approximately the same as the molar concentration of acid in the aerosol. 169. A cartridge according to any one of Embodiments 137-168, characterized in that the aerosol contains approximately 50% of the nicotine in the formulation, approximately 60% of the nicotine in the formulation, approximately 70% of the nicotine in the formulation, approximately 75% of the nicotine in the formulation, approximately 80% of the nicotine in the formulation, approximately 85% of the nicotine in the formulation, approximately 90% of the nicotine in the formulation, approximately 95% of the nicotine in the formulation, or approximately 99% of the nicotine in the formulation. 170. Aerosols range from approximately 0.1 microns to approximately 5 microns, approximately 0.1 microns to approximately 4.5 microns, approximately 0.1 microns to approximately 4 microns, approximately 0.1 microns to approximately 3.5 microns, approximately 0.1 microns to approximately 3 microns, approximately 0.1 microns to approximately 2.5 microns, approximately 0.1 microns to approximately 2 microns, approximately 0.1 microns to approximately 1.5 microns, approximately 0.1 microns to approximately 1 micron, approximately 0.1 microns to approximately 0.9 microns, and approximately 0.1 A cartridge according to any one of Embodiments 137-169, characterized in that it contains a condensate in particle sizes ranging from a micron to about 0.8 microns, from about 0.1 microns to about 0.7 microns, from about 0.1 microns to about 0.6 microns, from about 0.1 microns to about 0.5 microns, from about 0.1 microns to about 0.4 microns, from about 0.1 microns to about 0.3 microns, from about 0.1 microns to about 0.2 microns, or from about 0.3 to about 0.4 microns. 171. A cartridge according to any one of embodiments 137-170, characterized in that the aerosol contains a condensate of nicotine salt. 172. A cartridge according to any one of embodiments 137-170, characterized in that the aerosol comprises a condensate containing one or more of a carrier, a nicotine salt, free base nicotine, and a free acid. 173. A cartridge according to any one of embodiments 137-172, characterized in that the acid does not decompose at room temperature and does not decompose at the operating temperature of the e-cigarette. 174. A cartridge according to any one of embodiments 137-173, characterized in that the operating temperature of the e-cigarette is between 150°C and 250°C. 175. A formulation according to any one of embodiments 69-105, characterized in that the operating temperature of the e-cigarette is between 180°C and 220°C. 176. A cartridge according to any one of embodiments 137-173, characterized in that the operating temperature of the e-cigarette is approximately 200°C. 177. A cartridge according to any one of embodiments 137-176, characterized in that the acid is stable at the operating temperature of the e-cigarette, or at about 200°C and below. 178. A cartridge according to any one of embodiments 137-176, characterized in that the acid does not decompose at the operating temperature of the e-cigarette, or at approximately 200°C and below. 179. A cartridge according to any one of embodiments 137-176, characterized in that the acid does not oxidize at the operating temperature of the e-cigarette, or at approximately 200°C, or below. 180. A cartridge according to any one of embodiments 137-179, characterized in that the formulation is non-toxic to the user of an e-cigarette. 181. A cartridge according to any one of embodiments 137-180, characterized in that the formulation does not corrode the e-cigarette. 182. A cartridge according to any one of embodiments 137-181, characterized in that the formulation contains a flavoring agent. 183. A cartridge according to any one of embodiments 137-182, characterized in that inhalation of an aerosol at a rate of one puff every 30 seconds for a period of 5 minutes results in a nicotine plasma Tmax of approximately 1 to 8 minutes. 184. Nicotine plasma Tmax is approximately 1 to 7 minutes, approximately 1 to 6 minutes, approximately 1 to 5 minutes, approximately 1 to 4 minutes, approximately 1 to 3 minutes, approximately 1 to 2 minutes, approximately 2 to 8 minutes, approximately 2 to 7 minutes, approximately 2 to 6 minutes, approximately 2 to 5 minutes, approximately 2 to 4 minutes, approximately 2 to 3 minutes, approximately 3 to 8 minutes, approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 minutes A cartridge according to Embodiment 183, characterized in that the operating time is approximately 7 minutes, 4 to 6 minutes, 4 to 5 minutes, 5 to 8 minutes, 5 to 7 minutes, 5 to 6 minutes, 6 to 8 minutes, 6 to 7 minutes, 7 to 8 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, less than 5 minutes, less than 4 minutes, less than 3 minutes, less than 2 minutes, less than 1 minute, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, or 1 minute. 185. Any one cartridge of Embodiments 137-182, characterized in that inhalation of an aerosol at a rate of one puff every 30 seconds for approximately 5 minutes results in a nicotine plasma Tmax of approximately 2 to 8 minutes. 186. Nicotine COMTmax is approximately 2 to 8 minutes, approximately 2 to 7 minutes, approximately 2 to 6 minutes, approximately 2 to 5 minutes, approximately 2 to 4 minutes, approximately 2 to 3 minutes, approximately 3 to 8 minutes, approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 to 7 minutes, approximately 4 to 6 minutes, approximately 4 to 5 minutes, approximately 5 minutes The cartridge according to Embodiment 185, characterized in that the operating time is approximately 8 minutes, 5 minutes to 7 minutes, 5 minutes to 6 minutes, 6 minutes to 8 minutes, 6 minutes to 7 minutes, 7 minutes to 8 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, less than 5 minutes, less than 4 minutes, less than 3 minutes, less than 2 minutes, less than 1 minute, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, or 2 minutes. 187. A cartridge according to any one of embodiments 137-182, characterized in that inhalation of an aerosol at a rate of one puff every 30 seconds for approximately 5 minutes results in a nicotine plasma Tmax of approximately 3 to 8 minutes. 188. The cartridge according to Embodiment 187, characterized in that the nicotine COMTmax is approximately 3 to 7 minutes, approximately 3 to 6 minutes, approximately 3 to 5 minutes, approximately 3 to 4 minutes, approximately 4 to 8 minutes, approximately 4 to 7 minutes, approximately 4 to 6 minutes, approximately 4 to 5 minutes, approximately 5 to 8 minutes, approximately 5 to 7 minutes, approximately 5 to 6 minutes, approximately 6 to 8 minutes, approximately 6 to 7 minutes, approximately 7 to 8 minutes, less than 8 minutes, less than 7 minutes, less than 6 minutes, less than 5 minutes, less than 4 minutes, approximately 8 minutes, approximately 7 minutes, approximately 6 minutes, approximately 5 minutes, approximately 4 minutes, or approximately 3 minutes. 189. A cartridge according to any one of embodiments 137-182, characterized in that Tmax is less than approximately 8 minutes. 190. A cartridge according to any one of embodiments 183-189, characterized in that Tmax is determined based on at least three independent datasets. 191. The cartridge according to embodiments 183-189, characterized in that Tmax is the range of at least three independent datasets. 192. The cartridge according to embodiments 183-189, characterized in that Tmax is the mean ± standard deviation of at least three independent datasets. 193. A cartridge according to any one of Embodiments 137-192, characterized in that the liquid carrier comprises glycerin, propylene glycol, trimethylene glycol, water, ethanol, or a combination thereof. 194. A cartridge according to any one of embodiments 137-192, characterized in that the liquid carrier contains propylene glycol and vegetable glycerin. 195. A cartridge according to any one of Embodiments 137-192, characterized in that the liquid carrier contains 20% to 50% propylene glycol and 80% to 50% vegetable glycerin. 196. A cartridge according to any one of Embodiments 137-192, characterized in that the liquid carrier contains 30% propylene glycol and 70% vegetable glycerin. 197. A cartridge according to any one of embodiments 137-196, characterized in that the formulation further comprises one or more additional acids. 198. The cartridge according to Embodiment 197, characterized in that one or more additional acids include one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 199. The cartridge according to Embodiment 197, characterized in that one or more additional acids include benzoic acid. 200. A cartridge according to any one of the embodiments 197-199, characterized in that one or more additional acids form one or more additional nicotine salts. 201. A cartridge for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the cartridge includes a fluid compartment formed to be in fluid communication with a heating element, the fluid compartment contains a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 0.5% (w / w) to approximately 20% (w / w) b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is approximately 0.25:1 to approximately 4:1; and c. A cartridge comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 202. A cartridge for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the cartridge includes a fluid compartment formed to be in fluid communication with a heating element, the fluid compartment contains a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is approximately 0.25:1 to approximately 4:1 and c. A cartridge comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 203. A cartridge for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the cartridge includes a fluid compartment formed to be in fluid communication with a heating element, the fluid compartment contains a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. An acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid, wherein the molar ratio of the acid to nicotine is about 1:1 to about 2:1; and c. A cartridge comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 204. A cartridge for use in a cryogenic electron vaporizer, i.e., an e-cigarette, wherein the cartridge includes a fluid compartment formed to be in fluid communication with a heating element, the fluid compartment contains a nicotine preparation, and the nicotine preparation is: a. Nicotine content ranging from approximately 2% (w / w) to approximately 6% (w / w); b. The molar ratio of benzoic acid to nicotine is approximately 1:1; and c. A cartridge comprising a biologically acceptable liquid carrier, wherein the operation of the e-cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation.

[0134] Preferred embodiments of the present invention are shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided merely as examples. Many modifications, changes, and substitutions will come to mind to those skilled in the art without departing from the present invention. It will be understood that various substitutes for the embodiments of the present invention described herein may be used when carrying out the present invention. The following embodiments define the scope of the present invention, and methods and structures within the scope of such embodiments, as well as their equivalents, are intended to be encompassed herein.

Claims

1. A method for producing an inhalable aerosol containing nicotine for delivery to a user, the method is: A process involving the use of a cryogenic electron vaporizer, i.e., an electronic cigarette, comprising a nicotine liquid preparation and a heater, wherein the nicotine liquid preparation comprises nicotine, acid, and a bioacceptable liquid carrier. The process of using an e-cigarette includes the step of supplying the amount of the nicotine liquid preparation to the heater; The method is characterized in that the heater heats an amount of the nicotine liquid preparation to form an aerosol, wherein at least about 50% of the acid in the amount is present in the aerosol, and at least about 90% of the nicotine in the amount is present in the aerosol.

2. The method according to claim 1, characterized in that the aforementioned amount comprises about 4 μL of the nicotine liquid preparation.

3. The method according to claim 1, characterized in that the aforementioned amount comprises approximately 4.5 mg of the nicotine liquid preparation.

4. The method according to any one of claims 1 to 3, characterized in that the concentration of nicotine is from about 0.5% (w / w) to about 20% (w / w).

5. The method according to any one of claims 1 to 4, characterized in that the molar ratio of the acid to the nicotine is from about 0.25:1 to about 4:

1.

6. The method according to any one of claims 1 to 5, characterized in that the acid comprises one or more acidic functional groups, and the molar ratio of the acidic functional groups to the nicotine is from about 0.25:1 to about 4:

1.

7. The method according to any one of claims 1 to 6, characterized in that the acid and the nicotine form a nicotine salt.

8. The method according to claim 7, characterized in that the nicotine is stable in the nicotine salt in the inhalable aerosol.

9. The method according to claim 7, characterized in that the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt.

10. The method according to any one of claims 1 to 9, characterized in that one or more particles of the inhalable aerosol are adjusted to a size for delivery to the user's lungs.

11. The method according to any one of claims 1 to 10, characterized in that the acid is selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, succinic acid, and citric acid.

12. The method according to any one of claims 1 to 10, characterized in that the acid is selected from the group consisting of benzoic acid, pyruvic acid, and salicylic acid.

13. The method according to any one of claims 1 to 10, characterized in that the acid is benzoic acid.

14. The method according to any one of claims 1 to 13, characterized in that the concentration is from about 2% (w / w) to about 6% (w / w).

15. The method according to any one of claims 1 to 13, characterized in that the concentration is approximately 5% (w / w).

16. The method according to any one of claims 1 to 15, characterized in that the bioacceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin.

17. The method according to any one of claims 1 to 15, characterized in that the bioacceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.

18. The method according to any one of claims 1 to 17, characterized in that the heater heats the amount of the nicotine liquid preparation to about 150°C to about 250°C.

19. The method according to any one of claims 1 to 17, characterized in that the heater heats the amount of the nicotine liquid preparation to about 180°C to about 220°C.

20. The method according to any one of claims 1 to 17, characterized in that the heater heats the amount of the nicotine liquid preparation to about 200°C.

21. The method according to any one of claims 1 to 20, characterized in that the nicotine liquid preparation further comprises an additional acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid.

22. The method according to claim 21, characterized in that the additional acid forms an additional nicotine salt.

23. The method according to any one of claims 1 to 22, characterized in that at least about 60% to about 90% of the acid in the aforementioned amount is present in the aerosol.

24. The method according to any one of claims 1 to 22, characterized in that at least about 70% to about 90% of the acid in the aforementioned amount is present in the aerosol.

25. The method according to any one of claims 1 to 22, characterized in that at least about 80% to about 90% of the acid in the aforementioned amount is present in the aerosol.

26. The method according to any one of claims 1 to 22, characterized in that more than about 90% of the acid in the aforementioned amount is present in the aerosol.

27. A method for producing an inhalable aerosol containing nicotine for delivery to a user, The process includes using a nicotine liquid preparation and a low-temperature electron vaporizer including a heater, i.e., an e-cigarette. Nicotine liquid preparations are a. Nicotine at concentrations ranging from approximately 0.5% (w / w) to approximately 20% (w / w), b. Acids having a molar ratio to nicotine of approximately 0.25:1 to approximately 4:1, and c. Containing a biologically acceptable liquid carrier, The process of using an e-cigarette includes the step of supplying the amount of the nicotine liquid preparation to the heater, A method characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, wherein at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

28. A method for producing an inhalable aerosol containing nicotine for delivery to a user, The process includes using a nicotine liquid preparation and a low-temperature electron vaporizer including a heater, i.e., an e-cigarette. Nicotine liquid preparations are a. Nicotine concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w), b. Acids having a molar ratio to nicotine of approximately 1:1 to approximately 4:1, and c. comprising a biologically acceptable liquid carrier, The process of using an e-cigarette includes the step of supplying the amount of the nicotine liquid preparation to the heater, A method characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, wherein at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

29. A method for producing an inhalable aerosol containing nicotine for delivery to a user, The process includes using a nicotine liquid preparation and a low-temperature electron vaporizer including a heater, i.e., an e-cigarette. Nicotine liquid preparations are a. Nicotine concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w), b. Acids having a molar ratio to nicotine of approximately 1:1 to approximately 4:1, and c. comprising a biologically acceptable liquid carrier, The process of using an e-cigarette includes the step of supplying the amount of the nicotine liquid preparation to the heater, A method characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, wherein at least about 90% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

30. A method for producing an inhalable aerosol containing nicotine for delivery to a user, The process includes using a nicotine liquid preparation and a low-temperature electron vaporizer including a heater, i.e., an e-cigarette. Nicotine liquid preparations are a. Nicotine concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w), b. Benzoic acid having a molar ratio of approximately 1:1 to nicotine, and c. comprising a biologically acceptable liquid carrier, The process of using an e-cigarette includes the step of supplying the amount of the nicotine liquid preparation to the heater, A method characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, wherein at least about 90% of the benzoic acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

31. A low-temperature electron vaporization device, that is, a cartridge for use in e-cigarettes, The cartridge includes a fluid compartment configured to communicate with a heating element and fluid, The fluid compartment comprises a nicotine preparation containing nicotine, acid, and a bioacidible liquid carrier. The step of using the electronic cigarette includes the step of supplying the amount of the nicotine liquid preparation to the heater, A cartridge characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, and at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

32. The cartridge according to claim 31, characterized in that the aforementioned amount contains approximately 4 μL of a nicotine liquid preparation.

33. The cartridge according to claim 31, characterized in that the aforementioned amount contains approximately 4.5 mg of a nicotine liquid preparation.

34. The cartridge according to any one of claims 31 to 33, characterized in that the nicotine concentration is from about 0.5% (w / w) to about 20% (w / w).

35. The cartridge according to any one of claims 31 to 34, characterized in that the molar ratio of the acid to the nicotine is from about 0.25:1 to about 4:

1.

36. The cartridge according to any one of claims 31 to 35, characterized in that the acid comprises one or more acidic functional groups, and the molar ratio of the acidic functional groups to the nicotine is from about 0.25:1 to about 4:

1.

37. The cartridge according to any one of claims 31 to 36, characterized in that the acid and the nicotine form a nicotine salt.

38. The cartridge according to claim 37, characterized in that the nicotine is stable in the nicotine salt in the inhalable aerosol.

39. The cartridge according to claim 37, characterized in that the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt.

40. The cartridge according to any one of claims 31 to 39, characterized in that one or more particles of the inhalable aerosol are sized to be delivered to the user's lungs.

41. The cartridge according to any one of claims 31 to 40, characterized in that the acid is selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, succinic acid, and citric acid.

42. The cartridge according to any one of claims 31 to 40, characterized in that the acid is selected from the group consisting of benzoic acid, pyruvic acid, and salicylic acid.

43. The cartridge according to any one of claims 31 to 40, characterized in that the acid is benzoic acid.

44. The cartridge according to any one of claims 31 to 43, characterized in that the concentration is approximately 2% (w / w) to approximately 6% (w / w).

45. The cartridge according to any one of claims 31 to 43, characterized in that the concentration is approximately 5% (w / w).

46. The cartridge according to any one of claims 31 to 45, characterized in that the bioacceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin.

47. The cartridge according to any one of claims 31 to 45, characterized in that the bioacceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.

48. The cartridge according to any one of claims 31 to 47, characterized in that the heater heats the amount of the nicotine liquid preparation to about 150°C to about 250°C.

49. The cartridge according to any one of claims 31 to 47, characterized in that the heater heats the amount of the nicotine liquid preparation to about 180°C to about 220°C.

50. The cartridge according to any one of claims 31 to 47, characterized in that the heater heats the amount of the nicotine liquid preparation to about 200°C.

51. The cartridge according to any one of claims 31 to 50, characterized in that the nicotine liquid preparation further comprises an additional acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid.

52. The cartridge according to claim 51, characterized in that the additional acid forms an additional nicotine salt.

53. The cartridge according to any one of claims 31-52, characterized in that at least about 60% to about 90% of the acid in the aforementioned amount is present in the aerosol.

54. The cartridge according to any one of claims 31 to 52, characterized in that at least about 70% to about 90% of the acid in the aforementioned amount is present in the aerosol.

55. The cartridge according to any one of claims 31 to 52, characterized in that at least about 80% to about 90% of the acid in the aforementioned amount is present in the aerosol.

56. The cartridge according to any one of claims 31 to 52, characterized in that more than about 90% of the acid in the aforementioned amount is present in the aerosol.

57. A low-temperature electron vaporization device, that is, a cartridge for use in e-cigarettes, The cartridge includes a fluid compartment configured to communicate with a heating element and fluid, The fluid compartment contains a nicotine liquid preparation. The nicotine liquid preparation is: a. Nicotine at concentrations ranging from approximately 0.5% (w / w) to approximately 20% (w / w); b. Acids having a molar ratio to nicotine ranging from approximately 0.25:1 to approximately 4:

1. and c. comprising a biologically acceptable liquid carrier, The use of the electronic cigarette includes providing the heater with the amount of the nicotine liquid preparation. A cartridge characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, and at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

58. A low-temperature electron vaporization device, that is, a cartridge for use in e-cigarettes, The cartridge includes a fluid compartment configured to communicate with a heating element and fluid, The fluid compartment contains a nicotine liquid preparation. The nicotine liquid preparation is: a. Nicotine at concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w); b. Acids with a molar ratio to nicotine ranging from approximately 1:1 to approximately 4:

1. and c. comprising a biologically acceptable liquid carrier; The use of the electronic cigarette includes providing the heater with the amount of the nicotine liquid preparation. A cartridge characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, and at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

59. A low-temperature electron vaporization device, that is, a cartridge for use in e-cigarettes, The cartridge includes a fluid compartment configured to communicate with a heating element and fluid, The fluid compartment contains a nicotine liquid preparation. The nicotine liquid preparation is: a. Nicotine at concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w), b. Acids with a molar ratio to nicotine ranging from approximately 1:1 to approximately 4:

1. and c. comprising a biologically acceptable liquid carrier, The use of the electronic cigarette includes providing the heater with the amount of the nicotine liquid preparation. A cartridge characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, and at least about 90% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

60. A low-temperature electron vaporization device, that is, a cartridge for use in e-cigarettes, The cartridge includes a fluid compartment configured to communicate with a heating element and fluid, The fluid compartment contains a nicotine liquid preparation. The nicotine liquid preparation is: a. Nicotine at concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w); b. Benzoic acid with a molar ratio of approximately 1:1 to nicotine, and c. comprising a biologically acceptable liquid carrier; The use of the electronic cigarette includes providing the heater with the amount of the nicotine liquid preparation. A cartridge characterized in that the heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, and at least about 90% of the benzoic acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

61. A low-temperature electron vaporization device including a heater, i.e., a formulation for use in an e-cigarette, The formulation comprises nicotine, acid, and a biologically acceptable liquid carrier; The use of an e-cigarette includes providing the heater with the amount of the nicotine liquid preparation. The heater heats the aforementioned amount of the nicotine liquid preparation to form an aerosol, and at least about 50% of the acid in the aforementioned amount is present in the aerosol. A formulation characterized in that approximately 90% of the nicotine is present in the aerosol.

62. The formulation according to claim 61, characterized in that the aforementioned amount contains approximately 4 μL of a nicotine liquid formulation.

63. The formulation according to claim 61, characterized in that the aforementioned amount contains approximately 4.5 mg of a nicotine liquid preparation.

64. The formulation according to any one of claims 61 to 63, characterized in that the concentration of nicotine is from about 0.5% (w / w) to about 20% (w / w).

65. The formulation according to any one of claims 61 to 64, characterized in that the molar ratio of the acid to the nicotine is from about 0.25:1 to about 4:

1.

66. The formulation according to any one of claims 61 to 65, characterized in that the acid comprises one or more acidic functional groups, and the molar ratio of the acidic functional groups to the nicotine is from about 0.25:1 to about 4:

1.

67. The formulation according to any one of claims 61 to 66, characterized in that the acid and the nicotine form a nicotine salt.

68. The formulation according to claim 67, characterized in that the nicotine is stable in the nicotine salt in the inhalable aerosol.

69. The formulation according to claim 67, characterized in that the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt.

70. The formulation according to any one of claims 61 to 69, characterized in that one or more particles of the inhalable aerosol are adjusted to a size for delivery to the user's lungs.

71. The formulation according to any one of claims 61 to 70, characterized in that the acid is selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, succinic acid, and citric acid.

72. The formulation according to any one of claims 61 to 70, characterized in that the acid is selected from the group consisting of benzoic acid, pyruvic acid, and salicylic acid.

73. The formulation according to any one of claims 61 to 70, characterized in that the acid is benzoic acid.

74. The formulation according to any one of claims 61 to 73, characterized in that the concentration is from about 2% (w / w) to about 6% (w / w).

75. The formulation according to any one of claims 61 to 73, characterized in that the concentration is approximately 5% (w / w).

76. The formulation according to any one of claims 61 to 75, characterized in that the bioacceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin.

77. The formulation according to any one of claims 61 to 75, characterized in that the bioacceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.

78. The formulation according to any one of claims 61 to 77, characterized in that the heater heats the amount of the nicotine liquid formulation to about 150°C to about 250°C.

79. The formulation according to any one of claims 61 to 77, characterized in that the heater heats the aforementioned amount of the nicotine liquid formulation to about 180°C to about 220°C.

80. The formulation according to any one of claims 61 to 77, characterized in that the heater heats the aforementioned amount of the nicotine liquid formulation to about 200°C.

81. The nicotine liquid preparation according to any one of claims 61 to 80, further comprising an additional acid selected from the group consisting of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid.

82. The formulation according to claim 81, characterized in that the additional acid forms an additional nicotine salt.

83. The formulation according to any one of claims 61 to 82, characterized in that at least about 60% to about 90% of the acid in the aforementioned amount is present in the aerosol.

84. The formulation according to any one of claims 61 to 82, characterized in that at least about 70% to about 90% of the acid in the aforementioned amount is present in the aerosol.

85. The formulation according to any one of claims 61 to 82, characterized in that at least about 80% to about 90% of the acid in the aforementioned amount is present in the aerosol.

86. The formulation according to any one of claims 61 to 82, characterized in that more than about 90% of the acid in the aforementioned amount is present in the aerosol.

87. A formulation for use in a low-temperature electron vaporization device including a heater, i.e., an e-cigarette, wherein the formulation is a. Nicotine concentrations ranging from approximately 0.5% (w / w) to approximately 20% (w / w); b. Acids in which the molar ratio of acid to nicotine is approximately 0.25:1 to approximately 4:

1. and c. comprising a biologically acceptable liquid carrier; The use of an e-cigarette includes supplying the heater with the amount of the nicotine liquid preparation. A formulation characterized in that the heater heats the aforementioned amount of the nicotine liquid formulation to form an aerosol, and at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

88. A formulation for use in a low-temperature electron vaporization device including a heater, i.e., an e-cigarette, wherein the formulation is a. Nicotine concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w); b. Acids in which the molar ratio of acid to nicotine is approximately 1:1 to approximately 4:

1. and c. comprising a biologically acceptable liquid carrier; The use of an e-cigarette includes supplying the heater with the amount of the nicotine liquid preparation. A formulation characterized in that the heater heats the aforementioned amount of the nicotine liquid formulation to form an aerosol, and at least about 50% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

89. A formulation for use in a low-temperature electron vaporization device including a heater, i.e., an e-cigarette, wherein the formulation is a. Nicotine concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w); b. Acids in which the molar ratio of acid to nicotine is approximately 1:1 to approximately 4:

1. and c. comprising a biologically acceptable liquid carrier; The use of an e-cigarette includes supplying the heater with the amount of the nicotine liquid preparation. A formulation characterized in that the heater heats the aforementioned amount of the nicotine liquid formulation to form an aerosol, and at least about 90% of the acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

90. A formulation for use in a low-temperature electron vaporization device including a heater, i.e., an e-cigarette, wherein the formulation is a. Nicotine concentrations ranging from approximately 2% (w / w) to approximately 6% (w / w); b. Benzoic acid in which the molar ratio of benzoic acid to nicotine is approximately 1:1, and c. comprising a biologically acceptable liquid carrier; The use of an e-cigarette includes supplying the heater with the amount of the nicotine liquid preparation. A formulation characterized in that the heater heats the aforementioned amount of the nicotine liquid formulation to form an aerosol, and at least about 90% of the benzoic acid in the aforementioned amount is present in the aerosol, and about 90% of the nicotine in the aforementioned amount is present in the aerosol.

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