Nicotine liquid formulations for aerosol devices and methods thereof

Abstract

To provide specific nicotine liquid formulations which provide an individual with better satisfaction than free base nicotine, and which provide an individual smoking a traditional cigarette with more comparable satisfaction.SOLUTION: A nicotine liquid formulation comprises nicotine, an acid, and a biologically acceptable liquid carrier. Heating an amount of the nicotine liquid formulation using a low temperature electronic vaporization device, i.e., an electronic cigarette, generates inhalable aerosol. At least about 50% of the acid in the amount is in the aerosol. At least about 90% of the nicotine in the amount is in the aerosol.SELECTED DRAWING: Figure 1

Description

[Technical field]

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

[0002] Summary of the Invention In some embodiments, provided herein is a method of generating an inhalable aerosol comprising nicotine for delivery to a user, the method comprising using a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, the nicotine liquid formulation comprising nicotine, an acid and a biologically acceptable liquid carrier, the step of using the e-cigarette comprising providing a quantity of the nicotine liquid formulation to the heater, the heater heating the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the quantity is in the aerosol and at least about 90% of the nicotine in the quantity is 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 is from about 0.5% (w / w) to about 20% (w / w). In some embodiments, the molar ratio of the acid to the nicotine is 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 is 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 lungs of the user. 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 about 5% (w / w). In some embodiments of the methods described herein, the biologically acceptable 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 biologically acceptable 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 amount of the acid is in the aerosol. In some embodiments of the methods described herein, at least about 70% to about 90% of the amount of the acid is in the aerosol. In some embodiments of the methods described herein, at least about 80% to about 90% of the acid in the amount is in the aerosol. In some embodiments of the methods described herein, greater than about 90% of the acid in the amount is in the aerosol.

[0004] In some embodiments, provided herein is a method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising using a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of from about 0.5% (w / w) to about 20% (w / w), an acid having a molar ratio to said nicotine of from about 0.25:1 to about 4:1, and a biologically acceptable liquid carrier, wherein using the e-cigarette comprises providing an amount of said nicotine liquid formulation to said heater, said heater heating said amount of said nicotine liquid formulation to form an aerosol, wherein at least about 50% of said acid in said amount is in said aerosol, and about 90% of said nicotine in said amount is in said aerosol.

[0005] In some embodiments, provided herein is a method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising using a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of from about 2% (w / w) to about 6% (w / w), an acid having a molar ratio to said nicotine of from about 1:1 to about 4:1, and a biologically acceptable liquid carrier, wherein using the e-cigarette comprises providing an amount of said nicotine liquid formulation to said heater, said heater heating said amount of said nicotine liquid formulation to form an aerosol, wherein at least about 50% of said acid in said amount is in said aerosol, and about 90% of said nicotine in said amount is in said aerosol.

[0006] In some embodiments, provided herein is a method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising using a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine at a concentration of from about 2% (w / w) to about 6% (w / w), an acid having a molar ratio to said nicotine of from about 1:1 to about 4:1, and a biologically acceptable liquid carrier, wherein using the e-cigarette comprises providing an amount of said nicotine liquid formulation to said heater, said heater heating said amount of said nicotine liquid formulation to form an aerosol, wherein at least about 90% of said acid in said amount is in said aerosol, and wherein about 90% of said nicotine in said amount is in said aerosol.

[0007] In some embodiments, provided herein is a method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising using a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, wherein the nicotine liquid formulation comprises nicotine in a concentration of about 2% (w / w) to about 6% (w / w), benzoic acid in a molar ratio to said nicotine of about 1:1, and a biologically acceptable liquid carrier, wherein using the e-cigarette comprises providing an amount of said nicotine liquid formulation to said heater, said heater heating said amount of said nicotine liquid formulation to form an aerosol, wherein at least about 90% of said benzoic acid in said amount is in said aerosol, and wherein about 90% of said nicotine in said amount is in said aerosol.

[0008] In some embodiments, provided herein is a cartridge for use in a low temperature electronic vaporization device, i.e., an e-cigarette, the cartridge including a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment including a nicotine formulation including the nicotine, an acid, and a biologically acceptable liquid carrier, the e-cigarette providing a quantity of the nicotine liquid formulation to the heater, the heater heating the quantity of the nicotine liquid formulation to form an aerosol, at least about 50% of the acid in the quantity is in the aerosol, and about 90% of the nicotine in the quantity is in the aerosol.

[0009] In some embodiments of the cartridges described herein, the amount comprises about 4 μL of the nicotine liquid formulation. In some embodiments of the cartridges described herein, the amount comprises about 4.5 mg of the nicotine liquid formulation. In some embodiments of the cartridges described herein, the concentration of the nicotine is 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 is 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 is 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 for delivery to the lungs of the user. 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 biologically acceptable 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 biologically acceptable 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 amount is in the aerosol. In some embodiments of the cartridges described herein, at least about 70% to about 90% of the acid in the amount is in the aerosol. In some embodiments of the cartridges described herein, at least about 80% to about 90% of the acid in the amount is in the aerosol. In some embodiments of the cartridges described herein, more than about 90% of the acid in the amount is in the aerosol.

[0010] In some embodiments, provided herein is a cartridge for use in a low temperature electronic vaporization device, 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 comprising: nicotine at a concentration of from about 0.5% (w / w) to about 20% (w / w); an acid having a molar ratio to nicotine of from about 0.25:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 in the aerosol, and about 90% of the nicotine in the amount is in the aerosol.

[0011] In some embodiments, provided herein is a cartridge for use in a low temperature electronic vaporization device, 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 comprising: nicotine at a concentration of from about 2% (w / w) to about 6% (w / w); an acid having a molar ratio to nicotine of from about 1:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 in the aerosol, and about 90% of the nicotine in the amount is in the aerosol.

[0012] In some embodiments, provided herein is a cartridge for use in a low temperature electronic vaporization device, 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 comprising: nicotine at a concentration of from about 2% (w / w) to about 6% (w / w); an acid having a molar ratio to nicotine of from about 1:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 in the aerosol, and about 90% of the nicotine in the amount is in the aerosol.

[0013] In some embodiments, provided herein is a cartridge for use in a low temperature electronic vaporization device, 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 comprising: nicotine at a concentration of from about 2% (w / w) to about 6% (w / w); benzoic acid in a molar ratio to nicotine of from about 1:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 benzoic acid in the amount is in the aerosol, and wherein about 90% of the nicotine in the amount is in the aerosol.

[0014] In some embodiments, provided herein is a formulation for use in a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a heater, the formulation comprising nicotine, an acid, and a biologically acceptable liquid carrier; using 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 in the aerosol, and about 90% of the nicotine in the amount is in the aerosol.

[0015] In some embodiments of the formulations described herein, the amount comprises about 4 μL of the nicotine liquid formulation. In some embodiments of the formulations described herein, the amount comprises about 4.5 mg of the nicotine liquid formulation. In some embodiments of the formulations described herein, the concentration of the nicotine is from about 0.5% (w / w) to about 20% (w / w). In some embodiments of the cartridges described herein, in some embodiments of the formulations described herein, the molar ratio of the acid to the nicotine is 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 is 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 lungs of the user. 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 biologically acceptable 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 biologically acceptable 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 amount is in the aerosol. In some embodiments of the formulations described herein, at least about 70% to about 90% of the acid in the amount is in the aerosol. In some embodiments of the formulations described herein, at least about 80% to about 90% of the acid in the amount is in the aerosol. In some embodiments of the formulations described herein, more than about 90% of the acid in the amount is in the aerosol.

[0016] In some embodiments, provided herein is a formulation for use in a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a heater, the formulation comprising nicotine at a concentration of from about 0.5% (w / w) to about 20% (w / w); an acid having a molar ratio of acid to nicotine of from about 0.25:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 in the aerosol and about 90% of the nicotine in the amount is in the aerosol.

[0017] In some embodiments, provided herein is a formulation for use in a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a heater, the formulation comprising nicotine at a concentration of from about 2% (w / w) to about 6% (w / w); an acid, the molar ratio of acid to nicotine being from about 1:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 in the aerosol and about 90% of the nicotine in the amount is in the aerosol.

[0018] In some embodiments, provided herein is a formulation for use in a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a heater, the formulation comprising nicotine at a concentration of from about 2% (w / w) to about 6% (w / w); an acid, the molar ratio of acid to nicotine being from about 1:1 to about 4:1, and a biologically acceptable liquid carrier; using 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 in the aerosol and about 90% of the nicotine in the amount is in the aerosol.

[0019] In some embodiments, provided herein is a formulation for use in a low temperature electronic vaporization device, i.e., an e-cigarette, comprising a heater, the formulation comprising nicotine at a concentration of from about 2% (w / w) to about 6% (w / w); benzoic acid, wherein the molar ratio of benzoic acid to nicotine is about 1:1, and a biologically acceptable liquid carrier; using 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 benzoic acid in the amount is in the aerosol, and wherein about 90% of the nicotine in the amount is in the aerosol.

[0020] <Incorporated by reference> All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0021] A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments in which the principles of the invention are utilized and the accompanying drawings of which: [Figure 1] Figure 1 shows a non-limiting example of the results of heart rate data measured over the first 6 minutes of inhalation. The Y-axis is heart rate (bpm) and the X-axis represents the time of the test (-60 to 180 seconds). [Diagram 2] Figure 2 shows the heart rate data measured over the first 10 minutes of smoking. The Y-axis is heart rate (bpm) and the X-axis represents the duration of the test (0-10 minutes). [Diagram 3] FIG. 3 shows a non-limiting example of the calculated vapor pressures of various acids relative to nicotine; [Figure 4] FIG. 4 illustrates a non-limiting example of a low-temperature electronic vaporization device (i.e., an e-cigarette) having a fluid storage compartment that contains a nicotine liquid formulation of embodiments herein; and [Diagram 5]FIG. 5 illustrates a non-limiting example of a low-temperature electronic vaporization device (i.e., e-cigarette) having a fluid storage compartment, a heater, and a cartomizer containing a nicotine liquid formulation of embodiments herein; [Figure 6] FIG. 6 depicts non-limiting examples of pharmacokinetic profiles of four test articles in a plasma study. [Figure 7] FIG. 7 depicts non-limiting examples of Cmax for four test articles in plasma studies. [Figure 8] FIG. 8 depicts a non-limiting example of Tmax for four test articles in a plasma study. [Figure 9] FIG. 9 depicts a non-limiting example of the correlation between the molar ratio of benzoic acid to nicotine and the percent of nicotine captured from at least a portion of the aerosol generated from a low temperature electronic volatilization device, i.e., an e-cigarette, and from a nicotine liquid formulation. [Figure 10] FIG. 10 depicts a non-limiting example of the percent 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 a nicotine liquid formulation. [Figure 11] FIG. 11 depicts a non-limiting correlation between the molar ratio of acidic functional groups to nicotine and the percent 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 from a nicotine liquid formulation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

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

[0023] It has been unexpectedly discovered herein that certain nicotine liquid formulations provide greater satisfaction in individuals than free base nicotine, and more comparable satisfaction in individuals smoking conventional cigarettes. The satisfaction effect is consistent with efficient transfer of nicotine to the lungs, as shown, for example, but not limited to, at least in Examples 8, 13, and 14, by the sharp increase in nicotine absorption in the alveoli and plasma of the individual's lungs. It has also been unexpectedly discovered herein that certain nicotine liquid formulations provide greater satisfaction than other nicotine liquid formulations. Such an effect is shown, for example, but not limited to, in the plasma levels of the nicotine liquid formulations of the examples herein, at least in Examples 3 and 8. These results demonstrate that the rate of nicotine uptake in the blood is higher for nicotine liquid formulations, such as nicotine salt liquid formulations, than for nicotine free base formulations. Furthermore, the studies depicted herein demonstrate that the transfer efficiency of nicotine liquid formulations, such as nicotine salts, depends on the acid used in the formulation. As demonstrated at least in non-limiting manner in Example 13, certain acids used in nicotine liquid formulations result in better transfer from the liquid formulation to vapor and / or aerosol. Thus, described herein are nicotine liquid formulations, such as nicotine salt liquid formulations, for use in low-temperature electronic vaporization devices, i.e., e-cigarettes, and the like, that provide a generally satisfying effect consistent with efficient transfer of nicotine to the individual's lungs and a sharp increase in nicotine absorption in the plasma. Thus, provided herein are liquid formulations, systems, cartomizers, kits, and methods comprising one or more nicotine salts, used to inhale aerosol generated from a nicotine salt liquid formulation in a low-temperature electronic vaporization device, such as an e-cigarette, through the mouth or nose, as described herein or as would be apparent to one of ordinary skill in the art upon reading the disclosures herein.

[0024] Consistent with these gratification effects, it has been unexpectedly discovered herein that there are differences between the Cmax and Tmax of free-base nicotine liquid formulations inhaled using a low-temperature vaporization device, i.e., an electronic cigarette, when measuring plasma nicotine levels, compared to the Cmax (maximum concentration) and Tmax (time at which the maximum concentration was measured) of conventional cigarettes (also measuring plasma nicotine levels). Consistent with these gratification effects, it has been unexpectedly discovered herein that there are differences between the Cmax and Tmax of free-base nicotine liquid formulations inhaled using a low-temperature vaporization device, i.e., an electronic cigarette, when measuring plasma nicotine levels, compared to the Cmax and Tmax of nicotine liquid formulations, such as nicotine salt liquid formulations inhaled using a low-temperature vaporization device, i.e., an electronic cigarette (also measuring plasma nicotine levels). Furthermore, it has been unexpectedly discovered that there are differences between the nicotine inhalation rates in the plasma of users inhaling free-base nicotine liquid formulations using a low-temperature vaporization device, i.e., an electronic cigarette, when compared to the nicotine inhalation rates in the plasma of users inhaling conventional cigarette smoke. Furthermore, it has been unexpectedly discovered that there is a difference between the nicotine inhalation rates in the plasma of users who inhale a free base nicotine liquid formulation using a low temperature volatilization device, i.e., an electronic cigarette, compared to the nicotine inhalation rates in the plasma of users who inhale a nicotine liquid formulation, such as a nicotine salt liquid formulation, using a low temperature volatilization device, i.e., an electronic cigarette.

[0025] In some embodiments, inhalation of vapor and / or aerosol generated using a free base nicotine composition in a low temperature vaporization device, i.e., an electronic cigarette, is not necessarily comparable in plasma levels (Cmax and Tmax) to the nicotine delivery to the blood when a conventional cigarette is inhaled. In some embodiments, inhalation of vapor and / or aerosol generated using a free base nicotine composition in a low temperature vaporization device, i.e., an electronic cigarette, is not necessarily comparable in plasma levels (Cmax and Tmax) to the inhalation of vapor and / or aerosol containing nicotine generated from a nicotine liquid formulation, e.g., a nicotine salt liquid formulation. Furthermore, inhalation of vapor and / or aerosol generated using a free base nicotine composition in a low temperature vaporization device, i.e., an electronic cigarette, is not necessarily comparable in plasma levels to the nicotine delivery to the blood of a conventional cigarette when inhaled, when measuring the rate of nicotine inhalation in the blood during the first 0-8 minutes. Furthermore, inhalation of vapor and / or aerosol produced using free base nicotine compositions in low temperature vaporization devices, i.e., electronic cigarettes, is not necessarily comparable in plasma levels to inhalation of nicotine-containing vapor and / or aerosol produced from a nicotine liquid formulation, such as a nicotine salt liquid formulation, as measured by the rate of nicotine inhalation in the blood during the first 0-8 minutes.

[0026] The transfer efficiency of the nicotine liquid formulation delivers more nicotine from the liquid formulation to the vapor and / or aerosol, consistent with the observed differences in plasma levels when free base nicotine is used as a nicotine source in a low temperature vaporization device, i.e., an e-cigarette, as compared to a nicotine liquid formulation, such as a nicotine salt liquid formulation. As demonstrated, non-limiting Example 13, in which free base nicotine is used as a nicotine source in a low temperature electronic vaporization device, i.e., an e-cigarette, results in less nicotine being present in the aerosol, compared to a nicotine liquid formulation, such as a nicotine salt liquid formulation, used as a nicotine source in a low temperature electronic vaporization device, i.e., an e-cigarette. Moreover, this is consistent with the observed differences in nicotine plasma levels when free base nicotine is used as a nicotine source in a low temperature vaporization device, i.e., an e-cigarette, as compared to a nicotine liquid formulation, such as a nicotine salt liquid formulation, resulting in a more efficient transfer of nicotine from liquid to vapor and / or aerosol, resulting in a more efficient uptake of nicotine into the blood. One explanation for this observation is that the aerosol containing nicotine, e.g., aerosol droplets, are readily delivered to the user's lungs and / or alveoli therein, resulting in efficient uptake by the user's bloodstream. Moreover, the aerosol is delivered as particles sized to be delivered via the oral or nasal passages to the user's lungs, e.g., the alveoli of the user's lungs.

[0027] Compared with vaporized nicotine, aerosolized nicotine is more suitable to travel to the lungs of the user and be absorbed into the alveoli. One reason why aerosolized nicotine has a greater chance of being absorbed into the lungs compared with vaporized nicotine is, for example, that vaporized nicotine has a greater chance of being absorbed by the tissues of the mouth and upper airways of the user. Furthermore, nicotine absorbed by the mouth and upper airways is less absorbed than nicotine absorbed by lung tissue, resulting in less satisfactory effects for the user. As shown at least in non-limiting Examples 8 and 13, when using a low-temperature electronic vaporization device, i.e., an e-cigarette, to deliver nicotine to a user, there is a direct correlation between the time to 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 with nicotine benzoate (1:1 nicotine:benzoic acid molar ratio) and nicotine malate (1:2 nicotine:malic acid molar ratio). Furthermore, as shown, but not limited to, in Example 8, the Tmax of the free base is longer compared to nicotine benzoate and nicotine malate as a result of less aerosolized nicotine being absorbed less rapidly into the user's lungs.

[0028] Compared to an acid that is not decomposed at room temperature and / or the operating temperature of the device, an acid that is decomposed at room temperature and / or the operating temperature of the device requires a higher molar ratio of acid to nicotine to transfer the same molar amount of acid from the liquid to the aerosol. Thus, in some embodiments, compared to an acid that is not decomposed at room temperature and / or the operating temperature of the device, an acid that is decomposed at room temperature and / or the operating temperature of the device requires twice the molar amount to generate an aerosol, in some embodiments, the non-gas phase of the aerosol (e.g., droplets), that contains the same molar amount of nicotine in the aerosol. As shown, but not limited to, in Example 13, the correlation between the molar ratio of benzoic acid to nicotine and the percentage of trapped acid demonstrates that more acid is in the aerosol, in some embodiments, the non-gas phase of the aerosol, thereby resulting in more nicotine being present in the aerosol, in some embodiments, the non-gas phase of the aerosol. Furthermore, malic acid is known to decompose at about 150° C., which is below the temperature at which low-temperature electronic vaporization devices (i.e., e-cigarettes) operate. Also, as shown, but not limited to, in Example 13, when malic acid is used in a nicotine liquid formulation, less than 50% of the malic acid in the liquid formulation is recovered. This is significantly different from the 90% of the benzoic acid in the liquid formulation recovered when benzoic acid is used in a nicotine liquid formulation. The lower percentage recovery of malic acid is likely due to the decomposition of malic acid. Thus, as shown in Example 13, about twice as much malic acid is required to generate an aerosol, in some embodiments, the non-gas phase of the aerosol, with the same molar amount of acid in the aerosol, as compared to benzoic acid. Thus, in the case of malic acid, twice as much nicotine is required to generate an aerosol, in some embodiments, the non-gas phase of the aerosol, with the same amount of nicotine in the aerosol. Furthermore, decomposition products of malic acid are likely present in the aerosol, which may result in an unpleasant experience for the user when using the device and the nicotine malic acid liquid formulation. In some embodiments, the unpleasant experience includes taste, neurological response, 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 lungs of the user. In some embodiments, the formulation comprises a 1:1 ratio of moles of acidic functional groups to moles of nicotine, such that nicotine is stable in the aerosol produced by a low-temperature electronic vaporizer, i.e., an e-cigarette. In some embodiments, the formulation comprises a 1:1 ratio of moles of carboxylic acid functional group hydrogen to moles of nicotine, such that nicotine is stable in the aerosol produced by a low-temperature electronic 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 groups 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 likely protonated by the acid.This further demonstrates that nicotine is likely delivered to the lungs of the user in a protonated form in the aerosol.

[0030] Some reasons for not using acids in nicotine liquid formulations are listed below. Other reasons for using certain acids in nicotine liquid formulations are unrelated to the rate of nicotine absorption. In some embodiments, acids that corrode or are incompatible with electronic vaporization device materials are not used in nicotine liquid formulations. As a non-limiting example, sulfuric acid corrodes and / or reacts with device components, making it unsuitable for inclusion in nicotine liquid formulations. In some embodiments, acids that are toxic to users of electronic vaporization devices are not useful in nicotine liquid formulations because they are not compatible with human digestion, ingestion, or inhalation. As a non-limiting example, sulfuric acid is one such acid, which, depending on the embodiment of the composition, is unsuitable for users of low-temperature electronic vaporization devices, i.e., e-cigarettes. In some embodiments, acids in nicotine liquid formulations that are bitter or otherwise bad tasting to users are not useful in nicotine liquid formulations. Non-limiting examples of such acids are high concentrations of acetic acid or citric acid. In some embodiments, acids that oxidize at room temperature and / or device operating temperatures are not included in the nicotine liquid formulation. Non-limiting examples of such acids include sorbic acid and malic acid, which are unstable at room temperature and / or the operating temperature of the device. Decomposition of the acid at room temperature or operating temperature may indicate that the acid is unsuitable for use in the formulations of the embodiments. As a non-limiting example, citric acid decomposes at 175° C., malic acid decomposes at 140° C., and the device operates at 200° C., making these acids unsuitable. In some embodiments, acids that have low solubility for the components of the composition are unsuitable for use in certain embodiments of the compositions herein. As a non-limiting example, nicotine bitartrate, which comprises nicotine and tartaric acid in a 1:2 molar ratio composition, does not produce solutions in propylene glycol (PG) or vegetable glycerin (VG) or any mixture of PG and VG at ambient conditions with concentrations of nicotine or more than 0.5% (w / w) and tartaric acid or more than 0.9% (w / w). As used herein, weight percentage (w / w) refers to the weight of an individual component 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 a vapor pressure of >20 mmHg@200°C, or a vapor pressure of 20 mmHg to 300 mmHg@200°C, or a vapor pressure of 20-200 mmHg@200°C, or a vapor pressure of 20-300 mmHg@200°C provide satisfaction that is comparable or closer to traditional cigarettes (as compared to other nicotine salt formulations or nicotine free base formulations). By way of non-limiting example, acids that meet one or more of the foregoing criteria include salicylic acid, sorbic acid, benzoic acid, lauric acid, and levulinic acid. In some embodiments, nicotine liquid formulations, such as nicotine salt liquid formulations, made using acids with a difference between the boiling point and the melting point of at least 50° C., a boiling point greater than 160° C., and a melting point less than 160° C., provide satisfaction comparable to or closer to that of traditional cigarettes (compared to other nicotine salt formulations or nicotine free base formulations). By way of non-limiting example, acids that meet the aforementioned 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, made using acids with a difference between the boiling point and the melting point of at least 50° C., a boiling point at most 40° C. lower than the operating temperature, and a melting point at least 40° C. lower than the operating temperature, provide satisfaction comparable to or closer to that of traditional cigarettes (compared to other nicotine salt formulations or nicotine free base formulations). In some embodiments, the operating temperature can be from 100° C. to 300° C., or about 200° C., from about 150° C. to about 250° C., from 180° C. to 220° C., from about 180° C. to about 220° C., from 185° C. to about 215° C., from about 185° C. to about 215° C., from 190° C. to 210° C., from about 190° C. to about 210° C., from 195° C. to 205° C., or from about 195° C. to about 205° C. By way of non-limiting example, acids that meet the aforementioned criteria include salicylic acid, sorbic acid, benzoic acid, pyruvic acid, lauric acid, and levulinic acid. In some embodiments, combinations of these criteria with respect to the desirability of a particular nicotine salt formulation are incorporated herein.

[0032] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

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

[0034] The term "organic acid" as used herein refers to an organic compound with acidic properties (e.g., according to the Bronsted-Lowry definition or the Lewis definition). A typical organic acid is a carboxylic acid that associates its acidity with a carboxyl group -COOH. A dicarboxylic acid has two carboxylic acid groups. The relative acidity of an organic substance is measured by its pKa value, and one skilled in the art knows how to determine the acidity of an organic acid based on its given pKa value. The term "keto acid" as used herein refers to an organic compound that contains a carboxylic acid group and a ketone group. Common types of keto acids include alpha-keto acids (or 2-oxo acids) such as pyruvic acid or oxaloacetic acid, which have a keto group adjacent to the carboxylic acid; beta-keto acids (or 3-oxo acids) such as acetoacetic acid, 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] The term "electronic cigarette" or "cold vaporizer" as used herein refers to an electronic inhaler that vaporizes a liquid solution into an aerosol mist, mimicking the act of smoking a cigarette. The liquid solution includes a formulation that contains nicotine. There are many cold vaporizers, i.e., electronic cigarettes, that are not at all similar to traditional cigarettes. The user can choose the amount of nicotine contained by inhaling. Generally, cold vaporizers (i.e., electronic cigarettes) include three essential components: a plastic cartridge that serves as a mouthpiece and a reservoir for the liquid, an "atomizer" that converts the liquid into vapor, and a battery. In other embodiments, the cold vaporizers (i.e., electronic cigarettes) include a combined atomizer and reservoir called a "cartomizer," which may or may not be disposable, a mouthpiece that may or may not be integrated into the cartomizer, and a battery.

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

[0037] Suitable carriers (e.g., liquid solvents) for the nicotine salts described herein include media in which the nicotine salt is soluble at ambient conditions such that the nicotine salt does not form a solid precipitate. Examples include, but are not limited to, glycerin, propylene glycol, trimethylene glycol, water, ethanol, and the like, combinations thereof, and the like. In some embodiments, the liquid carrier comprises from about 0% to about 100% propylene glycol and from about 100% to about 0% vegetable glycerin. In some embodiments, the liquid carrier comprises from about 10% to about 70% propylene glycol and from about 90% to about 30% vegetable glycerin. In some embodiments, the liquid carrier comprises from about 20% to about 50% propylene glycol and from about 80% to about 50% vegetable glycerin. In some embodiments, the liquid carrier comprises from about 30% propylene glycol and from about 70% vegetable glycerin.

[0038] The formulations described herein vary in nicotine concentration. In some formulations, the nicotine concentration in the formulation is dilute. In some formulations, the nicotine concentration in the formulation is not too dilute. In some formulations, the nicotine concentration in the nicotine liquid formulation is from about 1% (w / w) to about 25% (w / w). In some formulations, the nicotine concentration in the nicotine liquid formulation is from about 1% (w / w) to about 20% (w / w). In some formulations, the nicotine concentration in the nicotine liquid formulation is from about 1% (w / w) to about 18% (w / w). In some embodiments, the nicotine concentration in the nicotine liquid formulation is from about 1% (w / w) to about 15% (w / w). In some formulations, the nicotine concentration in the nicotine liquid formulation is from about 4% (w / w) to about 12% (w / w). In some formulations, the concentration of nicotine in the nicotine liquid formulation is from about 2% (w / w) to about 6% (w / w). In some formulations, the concentration of nicotine in the nicotine liquid formulation is about 5% (w / w). In some formulations, the concentration of nicotine in the nicotine liquid formulation is about 4% (w / w). In some formulations, the concentration of nicotine in the nicotine liquid formulation is about 3% (w / w). In some formulations, the concentration of nicotine in the nicotine liquid formulation is about 2% (w / w). In some embodiments, the concentration of nicotine in the nicotine liquid formulation is about 1% (w / w). In some formulations, the concentration of nicotine in the nicotine liquid formulation is from about 1% (w / w) to about 25% (w / w).

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

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

[0041] In some embodiments, the formulation comprises an organic acid and / or an inorganic acid. In some embodiments, suitable organic acids include 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, hydroxycarboxylic acids, heterocyclic carboxylic acids, terpenoid acids, sugar acids such as pectic acid, amino acids, alicyclic acids, ketocarboxylic acids, and the like. 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 acid, salicylic acid, sorbic acid, malonic acid, malic acid, or combinations 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.

[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 a carboxylic acid. In some embodiments, the organic carboxylic acids disclosed herein are monocarboxylic acids, dicarboxylic acids (organic acids containing two carboxylic acid groups), and carboxylic acids containing aromatic groups such as benzoic acid, hydroxycarboxylic acids, heterocyclic carboxylic acids, terpenoid acids, sugar acids such as pectic acid, amino acids, alicyclic acids, ketocarboxylic acids, and the like. In some embodiments, the organic acids used herein are monocarboxylic acids. Nicotine salts are formed by the addition of a suitable acid to nicotine. 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, saccharic acid, salicylic acid, sorbic acid, masonic acid, malic acid, or combinations 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 and / or molar ratios of acid to nicotine, acidic functional groups to nicotine, and acidic functional hydrogen groups to nicotine. In some embodiments, the stoichiometric ratio of nicotine to acid (nicotine:acid) is 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 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 groups to nicotine in the formulation 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 hydrogen to nicotine in the formulation 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 acid 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 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 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 that contains two basic nitrogens. It can occur in different states of protonation. For example, when there is no protonation, nicotine is referred to as a "free base." When one nitrogen is protonated, nicotine is "mono-protonated."

[0045] In some embodiments, the nicotine liquid formulation is formed by adding a suitable acid to nicotine, stirring the suitable mixture at ambient or elevated 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. The dilution may be carried out at elevated temperature.

[0046] In some embodiments, the nicotine liquid formulation is prepared by combining nicotine and a suitable acid in a carrier mixture, such as a mixture of propylene glycol and glycerin. The mixture of nicotine and a 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 nicotine liquid formulation is prepared and added to a solution of propylene glycol (PG) / vegetable glycerin (VG) in a weight ratio of 3:7 and mixed thoroughly. Although described herein to produce 10 g of each formulation, all procedures described below are scalable. Other forms of formulation can be used to form the formulations described below, as will be understood by those skilled in the art upon reading the disclosure herein, without departing from the disclosure herein.

[0048] In some embodiments, the acid included in the nicotine liquid formulation is determined by the vapor pressure of the acid. In some embodiments, the nicotine liquid formulation includes an acid with a vapor pressure similar to that of the free base nicotine. In some embodiments, the nicotine liquid formulation is formed from an acid with a vapor pressure similar to that of the free base nicotine at the heating temperature of the device. As a non-limiting example, FIG. 3 shows this trend. Nicotine salts formed from nicotine and benzoic acid; nicotine and pyruvic acid; nicotine and salicylic acid; or nicotine and levulinic acid are salts that produce satisfaction in individual uses, consistent with efficient transfer of nicotine and a rapid rise in nicotine plasma levels. This pattern may be due to the mechanism of action during heating of the nicotine liquid formulation. Nicotine salts may dissociate at or slightly below the heating temperature of the device, resulting in a mixture of free base nicotine and the individual acids. At this point, if both nicotine and acid have similar vapor pressures, they will aerosolize simultaneously, resulting in transfer of free base nicotine and the constituent acids to the user. In some embodiments, a nicotine liquid formulation (e.g., a nicotine salt liquid formulation) may include a nicotine salt in a biologically acceptable liquid carrier for heating in a low temperature electronic vaporization device (i.e., an e-cigarette) to generate an inhalable aerosol, wherein the acid used to form the nicotine salt is characterized by a vapor pressure of between 20-4000 mmHg at 200° C. In some embodiments, the acid used to form the nicotine salt is characterized by a vapor pressure of between 20-2000 mmHg at 200° C. In some embodiments, the acid used to form the nicotine salt is characterized by a vapor pressure of between 100-300 mmHg at 200° C.

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

[0050] In some embodiments, monoprotonated nicotine salts produced high satisfaction in users. For example, nicotine benzoate and nicotine salicylate are monoprotonated nicotine salts that produce high satisfaction in users. The reason for this trend may be explained by the mechanism in which nicotine is first deprotonated before being transferred to vapor with the constituent acid, and then stabilized by the acid in the aerosol after reprotonation and carried by the acid down the stream to the lungs of the user. In addition, the lack of satisfaction of free base nicotine indicates that a second factor may be important. Depending on the salt, nicotine salts perform best when they are in the optimal range of protonation. For example, as depicted in non-limiting Example 13, nicotine benzoate at a 1:1 ratio of benzoic acid to nicotine transfers the maximum amount of nicotine to the aerosol. Lower molar ratios result in less nicotine being transferred to the aerosol, and going higher than the 1:1 molar ratio of benzoic acid to nicotine does not result in more nicotine being transferred to the aerosol. This can be explained by the fact that one mole of nicotine associates or interacts with one 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 left unprotonated in the formulation will vaporize, resulting in less user satisfaction.

[0051] In some embodiments, acids that decompose at room temperature or at the operating temperature of a low-temperature electronic vaporizer (i.e., low-temperature e-cigarette) do not provide the same satisfaction to the user. For example, twice as much malic acid is required to transfer the same molar amount of acid from liquid to aerosol compared to benzoic acid, which is decomposed at the operating temperature of a low-temperature e-cigarette. Thus, in some embodiments, twice as much molar malic acid is required to generate an aerosol with the same molar amount of nicotine compared to benzoic acid in some embodiments in the non-gas phase of the aerosol. Furthermore, because malic acid contains two carboxylic acid groups and benzoic acid contains one, four times as much acidic functional group hydrogen is required when using malic acid in a nicotine liquid formulation compared to benzoic acid. Furthermore, because malic acid contains two carboxylic acid groups and benzoic acid contains one, four times as much acidic functional group hydrogen is required when using malic acid in a nicotine liquid formulation compared to benzoic acid. In some embodiments, one or more chemicals produced in the decomposition of the acid provide an unfavorable experience to the user. In some embodiments, the unpleasant experience includes taste, nerve response, and / or irritation of one or more of the oral cavity, upper respiratory tract, and / or lungs.

[0052] In some embodiments, provided herein are methods, systems, devices, formulations, and kits for generating an inhalable aerosol comprising nicotine for delivery to a user using an electronic vaporization device, i.e., an electronic cigarette, comprising a nicotine liquid formulation and a heater, the nicotine liquid formulation comprising nicotine, an acid, and a biologically acceptable liquid carrier, and a method of using the electronic cigarette comprising: providing an amount of the nicotine liquid formulation to the heater; and heating the amount of the nicotine liquid formulation, the heater forming 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 amount of the acid is present in the aerosol. In some embodiments, at least about 50% to about 90% of the amount of the acid is present in the aerosol. In some embodiments, at least about 50% to about 80% of the amount of the acid is present in the aerosol. In some embodiments, at least about 50% to about 70% of the amount of the acid is present in the aerosol. In some embodiments, at least about 50% to about 60% of the amount of the acid is present in the aerosol. In some embodiments, at least about 60% to about 99% of the amount of the acid is present in the aerosol. In some embodiments, at least about 60% to about 95% of the amount of the acid is present in the aerosol. In some embodiments, at least about 60% to about 90% of the amount of the acid is present in the aerosol. In some embodiments, at least about 60% to about 80% of the amount of the acid 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 sized to be delivered to the user's lungs (e.g., the alveoli of the user's lungs) via the mouth or nasal passages. In some embodiments, the aerosol generated 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 sized to be delivered to the user's lungs (e.g., the alveoli of the user's lungs) via the mouth or nasal passages. In some embodiments, the rate of absorption in the user's lungs (e.g., the alveoli of the user's lungs) is affected by the aerosol particle size. In some embodiments, the aerosol particles are of the following sizes: from about 0.1 microns to about 5 microns, from about 0.1 microns to about 4.5 microns, from about 0.1 microns to about 4 microns, from about 0.1 microns to about 3.5 microns, from about 0.1 microns to about 3 microns, from about 0.1 microns to about 2.5 microns, from about 0.1 microns to about 2 microns, from about 0.1 microns to about 1.5 microns, from about 0.1 microns to about 1 micron, from about 0.1 microns to about 0.9 microns, from about 0.1 microns 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. from about 0.2 microns to about 5 microns, from about 0.2 microns to about 4.5 microns, from about 0.2 microns to about 4 microns, from about 0.2 microns to about 3.5 microns, from about 0.2 microns to about 3 microns, from about 0.2 microns to about 2.5 microns, from about 0.2 microns to about 2 microns, from about 0.2 microns to about 1.5 microns, from about 0.2 microns to about 1 micron, from about 0.2 microns to about 0.9 microns, from about 0.2 microns to about 0.8 microns, from about 0.2 microns to about 0.7 microns, from about 0.2 microns to about 0.6 microns, from about 0.2 microns to about 0.5 microns, from about 0.2 microns to about 0.4 microns, from about 0.2 microns to about 0.3 microns, from about 0.3 microns to about 5 microns, from about 0.3 microns to about 4.5 microns, from about 0.3 microns to about 4 microns, about 0.3 microns to about 3.5 microns, about 0.3 microns to about 3 microns, about 0.3 microns to about 2.5 microns, about 0.3 microns to about 2 microns, about 0.3 microns to about 1.5 microns, about 0.3 microns to about 1 micron, about 0.3 microns to about 0.9 microns, about 0.3 microns to about 0.8 microns, about 0.3 microns to about 0.7 microns, about 0.3 microns to about 0.6 microns, about 0.3 microns to about 0.5 microns, about 0.3 microns from about 0.4, from about 0.4 microns to about 5 microns, from about 0.4 microns to about 4.5 microns, from about 0.4 microns to about 4 microns, from about 0.4 microns to about 3.5 microns, from about 0.4 microns to about 3 microns, from about 0.4 microns to about 2.5 microns, from about 0.4 microns to about 2 microns, from about 0.4 microns to about 1.5 microns, from about 0.4 microns to about 1 micron, from about 0.4 microns to about 0.9 microns, from about 0.4 microns to about 0.8 microns, from about 0.4 microns to about 0.7 microns from about 0.4 microns to about 0.6 microns, from about 0.4 microns to about 0.5 microns, from about 0.5 microns to about 5 microns, from about 0.5 microns to about 4.5 microns, from about 0.5 microns to about 4 microns, from about 0.5 microns to about 3.5 microns, from about 0.5 microns to about 3 microns, from about 0.5 microns to about 2.5 microns, from about 0.5 microns to about 2 microns, from about 0.5 microns to about 1.5 microns, from about 0.5 microns to about 1 micron, from about 0.5 microns to about 0.9 microns, from about 0.5 microns to about 1.5 microns, from about 0.5 microns to about 1 micron, from about 0.5 microns to about 0.9 microns, from about 0.5 microns to about 1.5 microns, from about 0.5 microns to about 1.5 microns, from about 0.5 microns to about 1 micron, from about 0.5 microns to about 1.5 microns ... from about 0.8 microns, from about 0.5 microns to about 0.7 microns, from about 0.5 microns to about 0.6 microns, from about 0.6 microns to about 5 microns, from about 0.6 microns to about 4.5 microns, from about 0.6 microns to about 4 microns, from about 0.6 microns to about 3.5 microns, from about 0.6 microns to about 3 microns, from about 0.6 microns to about 2.5 microns, from about 0.6 microns to about 2 microns, from about 0.6 microns to about 1.5 microns, from about 0.6 microns to about 1 micron, from about 0.6 microns to about 0.9 microns, about 0.6 microns to about 0.8 microns, about 0.6 microns to about 0.7 microns, about 0.8 microns to about 5 microns, about 0.8 microns to about 4.5 microns, about 0.8 microns to about 4 microns, about 0.8 microns to about 3.5 microns, about 0.8 microns to about 3 microns, about 0.8 microns to about 2.5 microns, about 0.8 microns to about 2 microns, about 0.8 microns to about 1.5 microns, about 0.8 microns to about 1 micron, about 0.8 microns to about 0.9 microns, about 0.9 microns to about 5 microns, about 0.9 microns to about 4.5 microns from about 0.9 microns to about 4 microns, from about 0.9 microns to about 3.5 microns, from about 0.9 microns to about 3 microns, from about 0.9 microns to about 2.5 microns, from about 0.9 microns to about 2 microns, from about 0.9 microns to about 1.5 microns, from about 0.9 microns to about 1 micron, from about 1 micron to about 5 microns, from about 1 micron to about 4.5 microns, from about 1 micron to about 4 microns, from about 1 micron to about 3.5 microns, from about 1 micron to about 3 microns, from about 1 micron to about 2.5 microns, from about 1 micron to about 2 microns, from about 1 micron to about 1.5 microns.

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

[0055] The flavor of the constituent acid used in the salt formation may be considered when selecting the acid. A suitable acid has minimal or no toxicity to humans at the concentrations used. A suitable acid is compatible with the components of the e-cigarette that it will or may come into contact with at the concentrations used. That is, such an acid is not degraded or otherwise reacts with the e-cigarette components that it will or may come into contact with. The aroma of the constituent acid used in the salt formation may be considered when selecting the appropriate acid. The concentration of the nicotine salt in the carrier may affect the satisfaction in an individual user. 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 an exogenous flavoring agent. In some embodiments, an acid with an unpleasant taste or odor is used in a minimal amount to mitigate such characteristics. In some embodiments, an exogenous acid with a pleasant odor or taste is added to the formulation. Examples of salts that can provide flavor and aroma to the primary aerosol at particular levels include nicotine acetate, nicotine oxalate, nicotine malate, nicotine isovalerate, nicotine lactate, nicotine citrate, nicotine phenylacetate, and nicotine myristate.

[0056] Nicotine liquid formulations can be heated in a low temperature electronic vaporizer (i.e., an e-cigarette) to generate an aerosol that can be inhaled. 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 intensity of the inhalation.

[0057] Formulations are described herein that include two or more nicotine salts. In some embodiments of formulations that include two or more nicotine salts, each individual nicotine salt is formed as described herein.

[0058] Nicotine liquid formulation, as used herein, 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, suspending agents, thickeners, and / or excipients. 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 administration of nicotine to the body (e.g., the lungs).

[0059] The nicotine in the nicotine liquid formulations provided herein is either naturally occurring nicotine (e.g., from extracts of nicotine-bearing 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., greater than about 80% pure, 85% pure, 90% pure, 95% pure, or 99% pure). In some embodiments, the nicotine for the nicotine liquid formulations provided herein is "clear water" in appearance to avoid or minimize the formation of tarry residues during the subsequent salt formation step.

[0060] The nicotine liquid formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein, in some embodiments, have a nicotine concentration of about 0.5% (w / w) to about 20% (w / w), the concentration being by weight (e.g., w / w) of nicotine relative to the total solution weight. In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 20% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 18% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 15% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 4% (w / w) to about 12% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 18% (w / w), about 3% (w / w) to about 15% (w / w), or about 4% (w / w) to about 12% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 0.5% (w / w) to about 10% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 0.5% (w / w) to about 5% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 0.5% (w / w) to about 4% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 0.5% (w / w) to about 3% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 0.5% (w / w) to about 2% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 0.5% (w / w) to about 1% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 10% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 5% (w / w).In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 4% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 3% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 1% (w / w) to about 2% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 2% (w / w) to about 10% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 2% (w / w) to about 5% (w / w). In certain embodiments, the nicotine liquid formulations provided herein have a nicotine concentration of about 2% (w / w) to about 4% (w / w). Certain embodiments are within the range of about 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%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9 ...4%, 5.5%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 5.9%, 5.1%, 5.2%, 5. Nicotine liquid formulations are provided having a nicotine concentration of 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 even higher, or including any increment. Some embodiments provide a nicotine liquid formulation with a nicotine concentration of about 5% (w / w). Some embodiments provide a nicotine liquid formulation with a nicotine concentration of about 4% (w / w). Some embodiments provide a nicotine liquid formulation with a nicotine concentration of about 3% (w / w). Some embodiments provide a nicotine liquid formulation with a nicotine concentration of about 2% (w / w). Some embodiments provide a nicotine liquid formulation with a nicotine concentration of about 1% (w / w). Some embodiments provide a nicotine liquid formulation with a nicotine concentration of about 0.5% (w / w).

[0061] The nicotine liquid formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein, in some embodiments, have a nicotine concentration of about 0.5% (w / w), about 1% (w / w), about 2% (w / w), about 3% (w / w), about 4% (w / w), about 5% (w / w), about 6% (w / w), about 7% (w / w), about 8% (w / w), about 9% (w / w), about 10% (w / w), about 11% (w / w), about 12% (w / w), about 13% (w / w), about 14% (w / w), about 15% (w / w), about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), or about 20% (w / w). In some embodiments, the nicotine liquid formulations used in the cold vaporization devices (i.e., e-cigarettes) described herein contain 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), 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 18 ... ) to about 10% (w / w), from about 0.5% (w / w) to about 8% (w / w), from about 0.5% (w / w) to about 7% (w / w), from about 0.5% (w / w) to about 6% (w / w), from about 0.5% (w / w) to about 5% (w / w), from about 0.5% (w / w) to about 4% (w / w), from about 0.5% (w / w) to about 3% (w / w), or from about 0.5% (w / w) to about 2% (w / w). In some embodiments, the nicotine liquid formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain 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), from about 1% (w / w) to about 20 ... from about 1% (w / w) to about 10% (w / w), from about 1% (w / w) to about 8% (w / w), from about 1% (w / w) to about 7% (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).In some embodiments, the nicotine liquid formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain nicotine at 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 formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain nicotine at 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 formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain nicotine at 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 formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain nicotine at 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 formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain nicotine at the following concentrations: from about 6% (w / w) to about 20% (w / w), from about 6% (w / w) to about 18% (w / w), from about 6% (w / w) to about 15% (w / w), from about 6% (w / w) to about 12% (w / w), from about 6% (w / w) to about 10% (w / w), from about 6% (w / w) to about 8% (w / w), from about 6% (w / w) to about 7% (w / w). In some embodiments, the nicotine liquid formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain nicotine at a concentration of from about 2% (w / w) to about 6% (w / w). In some embodiments, the nicotine liquid formulations used in the low temperature vaporization devices (i.e., e-cigarettes) described herein contain 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 changing the acid. In some embodiments, the flavor of the formulation is adjusted by adding an exogenous flavoring agent. In some embodiments, an acid having an unpleasant taste or odor is used in a minimal amount to mitigate such characteristics. In some embodiments, an exogenous acid having a pleasant odor or taste is added to the formulation. Examples of salts that can provide flavor and aroma to the primary aerosol at specific levels include nicotine acetate, nicotine oxalate, nicotine malate, nicotine isovalerate, nicotine lactate, nicotine citrate, nicotine phenylacetate, and nicotine myristate.

[0063] In some embodiments, acids suitable for nicotine liquid formulations have a vapor pressure of >20 mmHg at 200° C. and are non-corrosive to e-cigarettes or non-toxic to humans. In some embodiments, acids suitable for nicotine salt formation are 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, suitable acids for nicotine liquid formulations have a vapor pressure of 20-200 mmHg at 200° C. and are non-corrosive to e-cigarettes or non-toxic to humans. In some embodiments, suitable acids for nicotine salt formation are 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, and is non-corrosive to the e-cigarette or 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 no more than 40° C. lower than the operating temperature of the e-cigarette, a difference of at least 50° C. between the melting point and the boiling point, and is non-corrosive to the e-cigarette or 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 formulation does not decompose at the operating temperatures of an e-cigarette. In some embodiments, the acid suitable for nicotine salt formation does not oxidize at the operating temperatures of an 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 provide an unpleasant taste. In some embodiments, the acid suitable for nicotine salt formation has high solubility in liquid formulations used in low temperature electronic vaporization devices (i.e., e-cigarettes).

[0067] A low temperature electronic vaporization device, i.e., e-cigarette 2, provided herein has a fluid storage compartment 4 containing therein an embodiment of a nicotine liquid formulation of any embodiment described herein. An embodiment is shown in FIG. 4. The e-cigarette 2 of FIG. 4 includes a mouth end 6 and a charging end 8. The mouth end 6 includes a mouthpiece 10. The charging end 8 may connect to a battery or a charger or both, where the battery is within the body of the e-cigarette and the charger is separate from the battery and couples with the body or the battery to charge the battery. In some embodiments, the e-cigarette includes a rechargeable battery within the body 14 of the e-cigarette, and the charging end 8 includes a connection 12 for charging the rechargeable battery. In some embodiments, the e-cigarette includes a cartomizer including 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, such 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 low temperature electronic vaporization device, i.e., an e-cigarette 2, containing an embodiment of a nicotine liquid formulation described herein within the fluid storage compartment described herein. The embodiment of the cartomizer 18 of FIG. 5 includes a mouth end 6 and a connecting end 16. The connecting end 16 in the embodiment of FIG. 5 connects the cartomizer 14 to the low temperature electronic vaporization device, i.e., an e-cigarette, or a battery of the 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 low temperature electronic vaporization device, i.e., an e-cigarette, or the cartomizer can be coupled to the battery or body of the low temperature electronic vaporization device, i.e., an e-cigarette. In some embodiments, the mouthpiece is integral to the body of the e-cigarette. In some embodiments, including the embodiment of FIG. 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 nicotine liquid formulation Various nicotine liquid formulations were prepared and added to a 3:7 by weight ratio solution of propylene glycol (PG) / vegetable glycerin (VG) and mixed thoroughly. The examples shown below were used to make 10 g of each formulation. All procedures are scalable.

[0070] For example, to make nicotine liquid formulations having a final equivalent concentration of 2% (w / w) nicotine free base, the following procedure was applied to each individual formulation. - Nicotine benzoate formulation: 0.15g of benzoic acid was added to a beaker, then 0.2g 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 cooled to ambient conditions. 9.65g of PG / VG (3:7) solution was added to the orange nicotine benzoate formulation and the mixture was stirred until a visually homogenous formulation solution was achieved. - Nicotine benzoate formulation can also be made by adding 0.15 g of benzoic acid to a beaker, 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 homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine citrate formulation was made by adding 0.47g citric acid to a beaker, then adding 0.2g nicotine and 9.33g PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine malate formulation was made by adding 0.33g of malic acid to a beaker, then adding 0.2g of nicotine and 9.47g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. - Nicotine succinate formulation was made by adding 0.29 g succinic acid to a beaker, 0.2 g nicotine and 9.51 g PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine salicylate formulation was made by adding 0.17g of salicylic acid to a beaker, then adding 0.2g of nicotine and 9.63g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine salicylate formulation can also be made by adding 0.17g of salicylic acid to a beaker, then adding 0.2g of nicotine to the same beaker. The mixture was stirred at 90°C for 60 minutes until the salicylic acid was completely dissolved, forming an orange oily mixture. The mixture was cooled to ambient conditions or maintained at 90°C, when 9.63g of PG / VG (3:7) solution was added. The mixture was then stirred at 90°C until a visually homogenous formulation solution was achieved with no undissolved chemicals. - Nicotine free base formulation was made by adding 0.2 g of nicotine to a beaker and adding 9.8 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at ambient conditions for 10 minutes until a visually homogenous formulation solution was achieved.

[0071] For example, to make nicotine liquid formulations having a final isotonic concentration of 3% (w / w) nicotine free base, the following procedure was applied to each individual formulation. - Nicotine benzoate formulation: 0.23 g of benzoic acid was added to a beaker, followed by 0.3 g of nicotine in 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 conditions. 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 homogenous formulation solution was achieved. - Nicotine benzoate formulation can also be made by adding 0.23 g of benzoic acid to a beaker, 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 homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine citrate formulation was made by adding 0.71 g of citric acid to a beaker, 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 homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine malate formulation was made by adding 0.5g malic acid to a beaker, then adding 0.3g nicotine and 9.2g PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. - A nicotine levulinate formulation was made by adding 0.64 g of levulinic acid dissolved in a beaker, followed by 0.3 g of nicotine to the same beaker. The mixture was stirred at 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 at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved. - A nicotine pyruvate formulation was made by adding 0.33 g of pyruvic acid to a beaker, followed by 0.3 g of nicotine to the same beaker. The mixture was stirred at 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 at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved. - Nicotine succinate formulation was made by adding 0.44g succinic acid to a beaker, then adding 0.3g nicotine and 9.26g PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. - A nicotine salicylate formulation was made by adding 0.26 g of salicylic acid to a beaker, 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 homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine salicylate formulation can also be made by adding 0.26g of salicylic acid to a beaker, then adding 0.3g 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 cooled to ambient conditions or maintained at 90°C, at which time 9.44g of PG / VG (3:7) solution was added. The mixture was then stirred at 90°C until a visually homogenous formulation solution was achieved with no undissolved chemicals. - Nicotine free base formulation was made by adding 0.3 g of nicotine to a beaker, then adding 9.7 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at ambient conditions for 10 minutes until a visually homogenous formulation solution was achieved.

[0072] For example, to make nicotine liquid formulations having a final isotonic concentration of 4% (w / w) nicotine free base, the following procedure was applied to each individual formulation. - Nicotine Benzoate Formulation: 0.3g benzoic acid was added to a beaker, followed by 0.4g nicotine in 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 cooled to ambient conditions. 9.7g PG / VG (3:7) solution was added to the orange nicotine benzoate and the mixture was stirred until a visually homogenous formulation solution was achieved. -Nicotine benzoate formulations can also be made by adding 0.3 g of benzoic acid to a beaker, followed by 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 homogenous formulation solution was achieved with no undissolved chemicals. For example, to make nicotine liquid formulations with a final equimolar concentration of 5% (w / w) nicotine free base, the following procedure was applied to each individual formulation: - Nicotine benzoate formulation: 0.38 g of benzoic acid was added to a beaker, followed by 0.5 g of nicotine in 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 cooled to ambient conditions. 9.12 g of PG / VG (3:7) solution was added to the orange nicotine benzoate and the mixture was stirred until a visually homogenous formulation solution was achieved. - Nicotine benzoate formulation can also be made 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 homogenous formulation solution was achieved with no undissolved chemicals. - Nicotine malate formulation can be made by adding 0.83g of malic acid to a beaker, then adding 0.5g of nicotine and 8.67g of PG / VG (3:7) solution to the same beaker. The mixture is then stirred at 90°C for 60 minutes until a visually homogenous formulation solution is achieved with no undissolved chemicals. - A nicotine levulinate formulation was made by adding 1.07 g of levulinic acid dissolved in a beaker, followed by 0.5 g of nicotine in the same beaker. The mixture was stirred at 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 at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved. - A nicotine pyruvate formulation was made by adding 0.54 g of pyruvic acid to a beaker, followed by 0.5 g of nicotine to the same beaker. The mixture was stirred at 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 at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved. -Nicotine succinate formulation was made by adding 0.73 g succinic acid to a beaker, then adding 0.5 g nicotine and 8.77 g PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. - A nicotine salicylate formulation was made by adding 0.43g of salicylic acid to a beaker, then adding 0.5g of nicotine and 9.07g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at 90°C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals. -Nicotine salicylate formulation can also be made by adding 0.43g of salicylic acid to a beaker, then adding 0.5g 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 cooled to ambient conditions or maintained at 90°C, at which time 9.07g of PG / VG (3:7) solution was added. The mixture was then stirred at 90°C until a visually homogenous formulation solution was achieved with no undissolved chemicals. - Nicotine free base formulation was made by adding 0.5 g of nicotine to a beaker, then adding 9.5 g of PG / VG (3:7) solution to the same beaker. The mixture was then stirred at ambient conditions for 10 minutes until a visually homogenous formulation solution was achieved. Various formulations containing various nicotine salts may be prepared in the same or different concentrations of the nicotine liquid formulations described above, or other nicotine formulations as would be understood by one of skill in the art upon reading the disclosure herein.

[0073] Various formulations containing two or more nicotine salts can be prepared in a similar 3:7 ratio propylene glycol (PG) / vegetable glycerin (VG) solution. 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] Further, another exemplary formulation is provided. For example, 0.23 g of nicotine benzoate (1.33% w / w nicotine) (1:1 molar ratio of nicotine / benzoic acid), 0.25 g of nicotine salicylate (1.33% w / w nicotine) (1:1 molar ratio of nicotine / salicylic acid) and 0.28 g of nicotine pyruvate (1.34% w / w nicotine) (1:2 molar ratio of 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 of Nicotine Solution Via E-Cigarette Representative formulations of nicotine levulinate, nicotine benzoate, nicotine succinate, nicotine salicylate, nicotine malate, nicotine pyruvate, nicotine citrate, nicotine free base and propylene glycol controls were prepared as described in Example 1 in 3% w / w solutions and administered in the same manner to the same human subjects by a low-temperature electronic vaporization device, i.e., an e-cigarette. Approximately 0.5 ml of each solution was loaded into an "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 about 150°C to about 250°C, or about 180°C to about 220°C.

[0076] Heart rate measurements were taken for 6 min; starting 1 min before inhalation, continuing for 3 min during inhalation and 2 min after inhalation had ended. Test participants took 10 puffs in 3 min in each case. Basal heart rate was the average heart rate during the first minute before inhalation began. Heart rate after inhalation was averaged over 20 s intervals. Inhalations occurred every 20 s for a total of 3 min. Normalized heart rate was defined as the ratio between each individual heart rate data point and the basal heart rate. The final results are shown as normalized heart rates for the first 4 min shown in Figure 1.

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

[0078] Example 3: Satisfaction study of saline nicotine via electronic cigarettes In addition to the heart rate study shown in Example 2, the nicotine liquid formulations (using the 3% w / w nicotine liquid formulation as described in Example 1) were used to conduct a satisfaction study using 11 test participants. The test participants, low-temperature electronic vaporizer (i.e., e-cigarette) and / or traditional cigarette users, were required to abstain from nicotine intake for at least 12 hours prior to the test. The participant was asked to take 10 puffs (as used in Example 2) using a low-temperature electronic vaporizer (i.e., e-cigarette) for 3 minutes in each case and then to rate the level of physical and emotional satisfaction he or she felt on a scale of 0-10, with 0 being physically or emotionally unsatisfied. Then, using the ranking provided for each formulation, the formulation was ranked from 1-8, with 1 having the highest ranking and 8 having the lowest ranking. The rankings of each acid were then averaged across the 11 participants to generate the average rankings in Table 1. Nicotine benzoate, nicotine pyruvate, nicotine salicylate and nicotine levulinate all performed well, followed by nicotine malate, nicotine succinate and nicotine citrate.

[0079] [Table 1]

[0080] Based on satisfaction studies, nicotine salt formulations with acids having a vapor pressure of >20 mmHg@200° C., or between 20-200 mmHg@200° C., or between 100-300 mmHg@200° C., provide more satisfaction than others (other than pyruvic acid, which has a boiling point of 165° C.) For reference, it has been determined that salicylic acid has a vapor pressure of about 135.7 mmHg@200° C., benzoic acid has a vapor pressure of about 171.7 mmHg@200° C., and levulinic acid has a vapor pressure of about 149 mmHg@200° C.

[0081] Based on the satisfaction study, furthermore, nicotine liquid formulations, e.g., nicotine salt liquid formulations, that contain an acid that is decomposed at the operating temperatures of the device (i.e., malic acid) were ranked lower. However, nicotine liquid formulations, e.g., nicotine salt liquid formulations, that contain an acid that is not decomposed at the operating temperatures of the device (i.e., benzoic acid) were ranked higher. Thus, acids that are prone to decomposition are less preferred compared to acids that are not prone to decomposition at the operating temperatures of the device.

[0082] Example 4: Test Formulation 1 (TF1) The nicotine levulinate solution in glycerin containing the nicotine salt was used: 1.26 g (12.6% w / w) of 1:3 nicotine levulinate, 8.74 g (87.4% w / w) of glycerin - total weight 10.0 g.

[0083] Neat nicotine levulinate was added to the glycerin and mixed thoroughly. L-nicotine has a molar mass of 162.2g and the levulinic acid molar mass is 116.1g. For a 1:3 molar ratio, the percentage of nicotine in nicotine levulinate by weight is given by: 162.2g / (162.2g+(3×116.1g))=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 mixed thoroughly.

[0085] Example 6: Heart Rate Study of Nicotine Solution Via E-Cigarette Both formulations (TF1 and TF2) were administered to the same human subjects in the same manner by a low-temperature electronic vaporization device (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, depending on the atomizer. The operating temperature of the e-cigarette is from about 150°C to about 250°C or from about 180°C to about 220°C.

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

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

[0088] It is clear from FIG. 2 that the test formulation with nicotine levulinate (TF1) produces a faster increase in heart rate than nicotine alone (TF2). Moreover, TF1 more closely resembles the rate of increase of a cigarette. Other salts have also been tried and have been 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 practice of the present invention. For example, other keto acids (alpha-keto acids, beta-keto acids, gamma-keto acids, etc.), such as pyruvate, oxaloacetate, acetoacetate, etc. This experience of increased heart rate comparable to a traditional burned cigarette has not been demonstrated or identified in other e-cigarette devices. Nor has it been demonstrated or identified in a low-temperature tobacco vaporization device that does not burn tobacco, even when nicotine salts are used as additives to tobacco (a solution of nicotine salts of 20% (w / w) or more). Therefore, the results from this experiment were surprising and unexpected.

[0089] In addition, the data appear to correlate well with previous findings shown in FIG.

[0090] As previously described in the satisfaction study, nicotine salt formulations with acids having vapor pressures between 20-300 mmHg@200°C provide more satisfaction than the others, except for the nicotine liquid formulation made with pyruvic acid, which has a boiling point of 165°C, as described in Figure 3. Furthermore, based on the satisfaction study, nicotine liquid formulations, such as nicotine salt liquid formulations, that include acids that decompose at the device's operating temperature (i.e., malic acid) were ranked lower, and nicotine liquid formulations, such as nicotine salt liquid formulations, that include acids that do not decompose at the device's operating temperature (i.e., benzoic acid) were ranked higher. Thus, acids that are prone to decomposition at the device's operating temperature are less preferred, compared to acids that are not prone to decomposition. Based on the findings herein, these nicotine liquid formulations are expected to have one or more of the following properties: Vapor pressure between -20-300mmHg@200℃ -> Vapor pressure of 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 lower than 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 lower than 160°C; - A difference of at least 50°C between the boiling point and the melting point, with a boiling point at most 40°C lower than the operating temperature and a melting point at least 40°C lower than the operating temperature, and - Resistant to decomposition due to the operating temperatures of the device.

[0091] Tmax - Time to Maximum Blood Concentration: Based on the results established herein, users of low-temperature electronic vaporization devices (i.e., e-cigarettes) containing nicotine liquid formulations experience comparable rates of physical and emotional gratification from the use of formulations containing mixtures of nicotine salts prepared with appropriate acids that are at least 1.2 to 3 times faster than those using formulations containing free base nicotine. As shown in Figure 1: nicotine from the nicotine salt formulation appears to cause the heart to beat approximately 1.2 times the individual's normal heart rate approximately 40 seconds after the start of a puff; nicotine from the nicotine free base formulation appears to cause the heart to beat approximately 1.2 times the individual's normal heart rate approximately 110 seconds after the start of a puff; but there is a 2.75-fold difference in the time to achieve comparable initial gratification.

[0092] Moreover, it is not inconsistent with the data from Figure 2; here the data illustrates that at approximately 120 seconds (2 minutes), the test participants' heart rates reached a maximum of 105-110 bpm with either the traditional cigarette or the nicotine liquid formulation (TF1); those same participants' heart rates reached a maximum of approximately 86 bpm at approximately 7 minutes with the nicotine free base formulation (TF2); furthermore, there was a 1.2-fold greater effect difference with nicotine salt (and traditional cigarette) versus free base.

[0093] Furthermore, when considering peak satisfaction (achieved approximately 120 seconds after the start of a puff (time=0)) and the slope of the normalized heart rate lines, the approximate slopes of these nicotine liquid formulations over the free base nicotine formulations are in the range between 0.0054 hrn / sec and 0.0025 hrn / sec. In comparison, the slope of the line for the free base nicotine liquid formulation is approximately 0.002. This would suggest that the concentration of nicotine available to the user is delivered at a rate 1.25-2.7 times faster than the free base formulation.

[0094] In another metric; Cmax - maximum blood nicotine concentration; as exemplified above, a similar increase is expected to be measured in blood nicotine concentration, i.e., a comparable Cmax is obtained between a regular cigarette and the particular nicotine liquid formulation, but a lower Cmax is expected based on the discoveries herein, and could not be predicted based on known technology to date.

[0095] Similarly, certain nicotine liquid formulations having higher rates of blood nicotine uptake levels in the first half of the time are expected based on the discoveries herein, and would not have been expected based on known technology to date. Indeed, Example 8 presents data for two salt formulations that are consistent with these expectations, which would have been expected based on the discoveries and testing described herein, and compared to available technology to date.

[0096] Example 7: Heart Rate Study of Nicotine Solution Via E-Cigarette As described in Example 1, representative 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 controls were prepared and administered to the same human subjects in the same manner by a low-temperature electronic vaporization device, 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 is about 150°C to about 250°C or about 180°C to about 220°C.

[0097] Heart rate measurements were taken for 6 min; starting 1 min before inhalation, continuing for 3 min during inhalation and 2 min after inhalation had ended. Test participants took 10 puffs in 3 min in each case. Basal heart rate was the average heart rate during the first minute before inhalation. Heart rate after inhalation was averaged over a 20 s interval. Normalized heart rate was defined as the ratio between each individual heart rate data point and the basal heart rate. The final result was presented as normalized heart rate.

[0098] <Example 8: Blood concentration test> Blood concentration studies were conducted in 24 subjects (n=24). Four test articles were used in the study: one reference cigarette and three nicotine liquid formulations used in a low temperature electronic vaporization device (i.e., e-cigarette) with an e-cigarette operating temperature of about 150°C to about 250°C, or about 180°C to about 220°C. The reference cigarette was Pall Mall (New Zealand). Three nicotine liquid formulations were tested in the e-cigarette: 2% free base (w / w on nicotine basis), 2% benzoate (w / w on nicotine basis, 1:1 molar ratio of nicotine to benzoic acid), and 2% malate (w / w on nicotine basis, 1:2 molar ratio of nicotine to malic acid). The three nicotine liquid formulations were liquid formulations prepared as described in Example 1.

[0099] The concentration of nicotine in each formulation was confirmed using a UV spectrophotometer (Cary 60 manufactured by Agilent). Sample solutions for UV analysis were made by dissolving 20 mg of each formulation in 20 ml of 0.3% HCl in water. The sample solutions were then scanned in the UV spectrophotometer and the characteristic nicotine peak at 259 nm was used to quantitate 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 1:100 with 0.3% HCl in water. The reported nicotine concentrations for all formulations are within the range of 95-105% of the claimed concentration.

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

[0101] Literature results: C. Bullen et al, Tobacco Control 2010, 19:98-103 Tobacco (5 min. voluntary (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 min, n=10): Tmax=32.0 (18.7-45.3), Cmax=2.1 (1.0-3.1).

[0102] Cmax estimate for 2% nicotine blend: Cmax = mass consumed * strength * bioavailability / (volume of distribution * body * weight) = 40mg * 2% * 80% / (2.6L / kg * 75kg) = 3.3ng / mL

[0103] The Cmax of a 4% nicotine blend was evaluated: Cmax = mass consumed * strength * bioavailability / (volume of distribution * body * weight) = 40mg * 4% * 80% / (2.6L / kg * 75kg) = 6.6ng / mL.

[0104] The pharmacokinetic profile of the blood concentration study is shown in FIG. 6; it shows the blood nicotine concentration (ng / ml) over time after the first puff (inhalation) of aerosol from an e-cigarette or smoking a reference cigarette. Ten puffs were taken in 30 second intervals starting at time=0 and continuing for 4.5 minutes. It appears based on the data shown in FIG. 6, and in other studies herein, the free base formulation appears to be lower than others tested at multiple time points, and therefore is statistically different from the salt formulation and / or reference cigarette in terms of Cmax. Furthermore, one skilled in the art, upon viewing the disclosure herein, can appropriately inspire tests to determine statistically based differences between one or more formulations and cigarettes, or between these formulations in a low temperature electronic vaporizer, i.e., an e-cigarette. For ease of reference, Table 2 shows the amount of nicotine detected in each formulation and reference cigarette (as an average of all users), presented in ng / mL along with Cmax and Tmax. The data from these tables, along with the raw data, were used to generate FIGS. 6, 7, and 8.

[0105] [Table 2-1]

[0106] [Table 2-2]

[0107] A comparison of the Cmax and Tmax of the three nicotine liquid formulations and the reference cigarette is shown in FIG. 7. Due to the time limit of the washout period, the baseline blood nicotine concentrations (at t=-2 minus t=0 min) were higher in samples consumed at later times on the test day. The data in FIGS. 6-7 show the corrected blood nicotine concentration values ​​(i.e., the apparent blood nicotine concentration at each time point minus the baseline nicotine concentration of the same sample). FIG. 8 depicts the Tmax data calculated using the corrected blood nicotine concentrations. The reference cigarette, the nicotine liquid formulations containing nicotine benzoate, and the nicotine liquid formulations containing nicotine malate all showed a higher Cmax and a lower Tmax than the nicotine liquid formulation containing free base nicotine. The better performance of the nicotine liquid formulations containing nicotine benzoate and nicotine malate compared to free base nicotine is due to the superior transfer efficiency of the nicotine salts from the liquid to the 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 properties of the nicotine liquid formulations of the acids tested provide a plausible explanation as to how the blood concentration test data corroborates the lower ranking of malic acid compared to benzoic acid as described in Example 1. In the plasma experiments, the nicotine malate formulation contained a 1:2 molar ratio of nicotine to malic acid, and the nicotine benzoate formulation contained a 1:1 molar ratio of nicotine to benzoic acid. As explained below, extra malic acid is required for aerosolized nicotine because malic acid is decomposed at the operating temperatures of e-cigarettes. Thus, it is likely that aerosols generated using malic acid will contain decomposition products (which may result in an adverse experience for the user, thus resulting in a lower ranking). For example, the adverse experience may include flavor, neurological response, and / or irritation of one or more of the oral cavity, upper respiratory tract, and / or lungs.

[0109] <Example 9: Blood concentration test> Blood concentration studies were conducted in 24 subjects (n=24). Eight test substances were used in this study: one reference cigarette and seven blends delivered as aerosol to the user in a low-temperature electronic vaporization device (i.e., e-cigarette). The operating temperature of the e-cigarette is about 150°C to about 250°C, or about 180°C to about 220°C. The reference cigarette is 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 are liquid formulations prepared by a protocol similar to that described in Example 1 and below.

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

[0111] Example 10: Blood concentration test Blood concentration studies were performed in 24 subjects (n=24). Eleven test articles are used in this study. One reference cigarette and ten blends were delivered as aerosols to users in a low-temperature electronic vaporizer (i.e., e-cigarette). The reference cigarette is a Pall Mall (New Zealand). The operating temperature of the e-cigarette is about 150°C to about 250°C, or about 180°C to about 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 are liquid formulations prepared by a protocol similar to that described in Example 1 and below.

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

[0113] Example 11: Blood concentration test Blood concentration studies were performed in 24 subjects (n=24). Twenty-one test substances were used in the study: one reference cigarette and 20 blends were delivered as aerosol to the user in a low-temperature electronic vaporization device (i.e., e-cigarette). The reference cigarette was Pall Mall (New Zealand). The operating temperature of the e-cigarette is about 150°C to about 250°C, or about 180°C to about 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 20 blends are liquid formulations prepared by a protocol similar to that described in Example 1 and below.

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

[0115] Example 12: Blood concentration test Blood concentration studies were conducted in 24 subjects (n=24). Twenty-one test articles were used in the study: one reference cigarette and 20 blends were delivered as an aerosol to the user in a low-temperature electronic vaporization device (i.e., e-cigarette). The reference cigarette is Pall Mall (New Zealand). The operating temperature of an e-cigarette is about 150°C to about 250°C, or about 180°C to about 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 20 blends are liquid formulations prepared by a protocol similar to that described in Example 1 and below.

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

[0117] Example 13: Aerosolized Nicotine Salts Testing The experimental system included a glass bubbler (Bubbler-1), a Cambridge filter pad, and two glass bubblers (Trap-1 and Trap-2 connected in sequence) to capture any volatiles that pass through the filter pad. A low-temperature electronic volatilization device (i.e., an e-cigarette) was activated by a smoking machine connected to the inlet of Bubbler-1 and the outlet of Trap-2 under a designed puffing regime. The puffing regime included: sample=30, size=60cc, puff duration=number of puffs per 4 seconds. The trapping solvent included 0.3% HCl in water. The nicotine liquid formulations tested were: free base nicotine, nicotine benzoate with nicotine to acid molar ratios of 1:0.4, 1:0.7, 1:1, and 1:1.5, and nicotine malate with nicotine to acid molar ratios of 1:0.5 and 1:2. The formulations were produced using the procedures described in Example 1. In the experimental system, the gaseous (i.e., vapor) analyte was trapped by a bubbler.

[0118] The steps include: * weighing the following areas prior to beginning a puff: the e-cigarette filled with the nicotine liquid formulation, bubbler-1 filled with 35 ml of capture solvent, a 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 smoking regime described above. Each puff was followed by a puff of clean air of the same puff size and duration; *Weighing all parts of the smoking mechanism after the end. The inlet tubing of bubbler-1 was analyzed with 10 ml of trapping solvent in a 1 ml water drop. The total amount of solvent in bubbler-1 after a puff was calculated with correction for water loss from 60 puffs. The filter pad was cut in half and each half was extracted with 20 mL of trapping 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 trapping solvent. The back half of the pad holder was analyzed with 3 ml of trapping solvent; * Analyzing the solutions by 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> (Subject Retrieved) The recovered amount of each analyte (nicotine, benzoic acid, and malic acid) was calculated as the sum of the amounts analyzed from all sites. No analytes were detected in trap-1 or trap-2. Percent recovery was calculated by dividing the total recovered amount by the theoretical amount produced by the e-cigarette. Table 3 shows the percent recovery of nicotine in the nicotine free base liquid formulation, the nicotine benzoate liquid formulation, and the nicotine malate liquid formulation. Table 3 also shows the percent recovery of benzoic acid in the nicotine benzoate liquid formulation and the percent recovery of malic acid in the nicotine malate liquid formulation.

[0120] [Table 3]

[0121] The percent recovery of malic acid was significantly lower than that of nicotine and benzoic acid, and showed a large variability between sample replicates. Malic acid has been reported to decompose thermally at 150° C., a temperature lower than the operating temperature of typical e-cigarettes. The low recovery of malic acid found in the aerosol is consistent with the thermal instability of malic acid. This results in a lower effective nicotine to malic acid ratio in the aerosol compared to the ratio in the nicotine liquid formulation. Thus, the protonation state of nicotine is also lower in the aerosol, resulting in effectively less nicotine being present in the aerosol generated with the nicotine malic acid liquid formulation. The lower nicotine recovery in the case of the free base nicotine liquid formulation compared to the nicotine liquid formulation may be due to the sample collection and analytical procedures where a smaller portion of the gaseous nicotine escapes the smoking system.

[0122] (Volatile nicotine in aerosols) The amount of nicotine in the aerosol exiting the cold vaporizer, i.e., the e-cigarette, was tested by calculating the percent nicotine captured in bubbler-1 compared to the total recovered nicotine. Being non-volatile, benzoic acid is expected to be present in the particles (i.e., droplets) in the aerosol. Benzoic acid is therefore used as a particle marker for nicotine, since it is expected to protonate nicotine in a 1:1 molar ratio. This results in nicotine being 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 and the molar ratio of benzoic acid to nicotine in the nicotine liquid formulation (Figure 9). At a 1:1 molar ratio of nicotine to benzoic acid, nicotine was fully protonated and the least amount of vapor recovered in bubbler-1 was measured. Furthermore, at a 1:1.5 molar ratio of nicotine to benzoic acid, there was no further decrease in the amount of aerosolized nicotine detected. It should further be noted that a higher percentage of free base nicotine was recovered by bubbler-1 indicating that the higher concentration of vapor phase nicotine is the nicotine generated when using free base nicotine in the nicotine liquid formulation.

[0124] Theoretically, malic acid, a dibasic acid, protonates nicotine at a molar ratio of malic acid to nicotine 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 formulations to aerosols. Thus, given the low transfer efficiency of malic acid, the effective nicotine to malic acid ratio in the aerosol is 0.23 when produced using a nicotine liquid formulation containing a 1:0.5 molar ratio of nicotine to malic acid, and 0.87 when produced using a nicotine liquid formulation containing a 1:2 molar ratio of nicotine to malic acid. As expected, the percentage of acid captured in Publ-1 when using a nicotine liquid formulation containing a 1:0.5 molar ratio of nicotine to malic acid is between the percentage of acid recovered when using nicotine liquid formulations containing a 1:0.4 and 1:0.7 molar ratio of nicotine to benzoic acid. 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 was necessary for the nicotine to be fully protonated, leaving only 14.7% of the nicotine trapped in bubbler-1 (Figure 10).

[0125] Aerosolized nicotine that remains in the particles is likely to travel to the alveoli and enter the user's blood. Gaseous nicotine is deposited in the upper airways and has many opportunities to be absorbed at different rates from the deep lung gas exchange regions. Thus, using a nicotine liquid formulation with a 1:1 nicotine to benzoic acid or 1:2 nicotine to malic acid molar ratio, 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: Acidic Functional Group Requirement 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 sequence) to capture any volatiles that pass through the filter pad. A low-temperature electronic volatilization device (i.e., an e-cigarette) was activated by a smoking machine connected to the inlet of Bubbler-1 and the outlet of Trap-2 under a designed puffing regime. The puffing regime included: sample=30, size=60cc, puff duration=4 seconds, number of puffs per puff. The trapping solvent included 0.3% HCl in water. The nicotine liquid formulations tested were: free base nicotine, nicotine benzoate with nicotine to acid molar ratios of 1:0.4, 1:0.7, 1:1, and 1:1.5, and nicotine malate with nicotine to acid molar ratios of 1:0.5 and 1:2. The formulations were produced using the procedure described in Example 1. In the experimental system, the gaseous (i.e., vapor) analyte was trapped by a bubbler.

[0127] The steps include: * weighing the following areas prior to beginning a puff: the e-cigarette filled with the nicotine liquid formulation, bubbler-1 filled with 35 ml of capture solvent, a 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 smoking regime described above. Each puff was followed by a puff of clean air of the same puff size and duration; *Weighing all parts of the smoking mechanism after the end. The inlet tubing of bubbler-1 was analyzed with 10 ml of trapping solvent in a 1 ml water drop. The total amount of solvent in bubbler-1 after a puff was calculated with correction for water loss from 60 puffs. The filter pad was cut in half and each half was extracted with 20 mL of trapping 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 trapping solvent. The back half of the pad holder was analyzed with 3 ml of trapping solvent; * Analyzing the solutions by 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 exiting the cold vaporizer, i.e., the e-cigarette, was tested by calculating the percent nicotine captured in bubbler-1 compared to the total recovered nicotine. Being non-volatile, benzoic acid is expected to be present in the particles (i.e., droplets) in the aerosol. Benzoic acid is therefore used as a particle marker for nicotine, since it is expected to protonate nicotine in a 1:1 molar ratio. This results in nicotine being 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 and the molar ratio of benzoic acid to nicotine in the nicotine liquid formulation (Figure 9). At a 1:1 molar ratio of nicotine to benzoic acid, nicotine was fully protonated and the least amount of vapor recovered in bubbler-1 was measured. Furthermore, at a 1:1.5 molar ratio of nicotine to benzoic acid, there was no further decrease in the amount of aerosolized nicotine detected. It should further be noted that a higher percentage of free base nicotine was recovered by bubbler-1, indicating that the higher concentration of vapor phase nicotine is the nicotine generated when using free base nicotine 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 decomposition. Thus, nicotine liquid formulations produced using either acid will behave similarly and produce aerosols with approximately the same molar amount of nicotine in the aerosol. Thus, the same total amount of acid is recovered when either acid is used in a nicotine liquid formulation. As described differently, approximately the same percentage of succinic acid is recovered when using a nicotine succinate liquid formulation in an e-cigarette compared to the percentage of benzoic acid recovered when using a nicotine benzoate liquid formulation as described in Example 13. Therefore, the same percentage of nicotine is likely also captured in the bubbler-1 when using either succinic acid or benzoic acid in a nicotine liquid formulation.

[0131] Here, different molar ratios of acidic functional groups to moles of nicotine were examined. Since succinic acid is a dibasic acid, a 1:0.25 molar ratio of nicotine to succinic acid was expected to trap the same amount of acid in bubbler-1 as was trapped using a 1:0.5 molar ratio of nicotine to benzoic acid. Furthermore, approximately the same amount of acid was expected to trap in bubbler-1 as a 1:0.5 molar ratio of nicotine to succinic acid was expected to trap using a 1:1 molar ratio of nicotine to benzoic acid. As expected based on the amount of nicotine trapped in nicotine liquid formulations with nicotine to benzoic acid molar ratios of 1:0.4 and 1:0.7, the same percentage of acid is expected to be recovered in bubbler-1 when using a 1:0.25 molar ratio of nicotine to succinic acid in the nicotine liquid formulation (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] Thus, since succinic acid is a dibasic acid, one mole of succinic acid will likely protonate two moles of nicotine, thus stabilizing two moles of nicotine in the aerosol. As stated differently, compared to the use of benzoic acid in the nicotine liquid formulation used in the low-temperature electronic vaporization device (i.e., electronic cigarette), half the molar amount of succinic acid in the nicotine liquid formulation used in the low-temperature electronic vaporization device (i.e., electronic cigarette) is required to fully protonate nicotine and stabilize it in the aerosol. Furthermore, because an excess of succinic acid (1:2 molar ratio of nicotine to succinic acid) was included in the formulation, it is reasonable that succinic acid was ranked low in the satisfaction study described in Example 3, since an excess of succinic acid was likely delivered to the user, thus resulting in an unpleasant experience for the user. For example, the unpleasant experience includes flavor, nervous reaction, and / or one or more irritation of the oral cavity, upper airway, and / or lungs.

[0133] Further understanding may be gained through the intent of the numbered embodiments below; 1. A method for delivering nicotine to a user, comprising the steps of deploying a low-temperature electronic vaporization device, i.e., an e-cigarette, the e-cigarette comprising a nicotine formulation, the nicotine formulation comprising: a. about 0.5% (w / w) to about 20% (w / w) nicotine b. a molar ratio of acid to nicotine of about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 2. The method of embodiment 1, wherein the molar ratio of acidic functional groups to nicotine is from about 0.25:1 to about 4:1. 3. The method of any one of embodiments 1-2, wherein the acid and nicotine form a nicotine salt. 4. The method of any one of embodiments 1-7, wherein the nicotine formulation contains monoprotonated nicotine. 5. The method of any one of embodiments 1-4, wherein the aerosol comprises monoprotonated nicotine. 6. The method of any one of embodiments 1-5, wherein the aerosol is delivered to the user's lungs. 7. The method of embodiment 6, wherein the aerosol is delivered to the alveoli in the user's lungs. 8. The method of any one of embodiments 1-10, wherein nicotine is stable in a salt form in the aerosol. 9. The method of any one of embodiments 1-10, wherein nicotine is delivered in salt form in the aerosol. 10. The method of any one of embodiments 1-9, wherein the acid contains one carboxylic acid functional group. 11. The method of any one of embodiments 1-9, wherein the acid contains more than one carboxylic acid functional group. 12. The method according to any one of the preceding embodiments, 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, saccharic acid, salicylic acid, sorbic acid, malic acid, and malic acid. 13. The method of any one of embodiments 1-9, wherein the acid comprises one or more of a carboxylic acid, a dicarboxylic acid, and a keto acid. 14. The method of any one of embodiments 1-9, wherein 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 of any one of embodiments 1-9, wherein the acid comprises benzoic acid. 16. The method of any one of embodiments 1-11, wherein the molar ratio of acid to nicotine in the formulation 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. 17. The method of any one of embodiments 1-11, wherein the molar ratio of acidic functional groups to nicotine in the formulation 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. 18. The method of any one of embodiments 1-11, wherein the molar ratio of acidic functional group hydrogen to nicotine in the formulation 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. 19. The method of any one of embodiments 1-11, wherein the molar ratio of acid 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. 20. The method of any one of embodiments 1-11, wherein 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 of any one of embodiments 1-11, wherein 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. 22. Nicotine concentrations are approximately 0.5% (w / w), 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), The method according to any one of embodiments 1-paragraph

[0043] , characterized in that the concentration is about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), or about 20% (w / w). 23. The nicotine concentration is 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), From about 0.5% (w / w) to about 10% (w / w), from about 0.5% (w / w) to about 8% (w / w), from about 0.5% (w / w) to about 7% (w / w), from about 0.5% (w / w) to about 6% (w / w), from about 0.5% (w / w) to about 5% (w / w) From about 0.5% (w / w) to about 4% (w / w), from about 0.5% (w / w) to about 3% (w / w), Alternatively, the method according to any one of embodiments 1-paragraph

[0043] is characterized in that the concentration is from about 0.5% (w / w) to about 2% (w / w). 24. The nicotine concentration is 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), from about 1% (w / w) to about 10% (w / w), from about 1% (w / w) to about 8% (w / w), from about 1% (w / w) to about 7% (w / w), The method of any one of embodiments 1-paragraph

[0043] , wherein the concentration of the glycerol in the glycerol-containing medium is 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 of any one of embodiments 1-paragraph

[0043] , wherein the nicotine concentration is 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). 26. The method of any one of embodiments 1-paragraph

[0043] , wherein the nicotine concentration is 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). 27. The method of any one of embodiments 1-paragraph

[0043] , wherein the nicotine concentration is 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). 28. The method of any one of embodiments 1-paragraph

[0043] , wherein the nicotine concentration is 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). 29. The method of any one of embodiments 1-paragraph

[0043] , wherein the nicotine concentration is from about 6% (w / w) to about 20% (w / w), from about 6% (w / w) to about 18% (w / w), from about 6% (w / w) to about 15% (w / w), from about 6% (w / w) to about 12% (w / w), from about 6% (w / w) to about 10% (w / w), from about 6% (w / w) to about 8% (w / w), or from about 6% (w / w) to about 7% (w / w). 30. The method of any one of embodiments 1-4, wherein the nicotine concentration is from about 2% (w / w) to about 6% (w / w). 31. The method of any one of embodiments 1-4, wherein the nicotine concentration is about 5% (w / w). 32. A 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 of any one of embodiments 1-32, wherein the aerosol comprises about 50% of the nicotine in the formulation, about 60% of the nicotine in the formulation, about 70% of the nicotine in the formulation, about 75% of the nicotine in the formulation, about 80% of the nicotine in the formulation, about 85% of the nicotine in the formulation, about 90% of the nicotine in the formulation, about 95% of the nicotine in the formulation, or about 99% of the nicotine in the formulation. 34. The aerosol may be from about 0.1 microns to about 5 microns, from about 0.1 microns to about 4.5 microns, from about 0.1 microns to about 4 microns, from about 0.1 microns to about 3.5 microns, from about 0.1 microns to about 3 microns, from about 0.1 microns to about 2.5 microns, from about 0.1 microns to about 2 microns, from about 0.1 microns to about 1.5 microns, from about 0.1 microns to about 1 micron, from about 0.1 microns to about 0.9 microns, from about 0.1 microns to about 0.8 microns, 34. The method of any one of embodiments 1-33, comprising condensate in a particle size range of up to about 0.1 microns to about 0.7 microns, up to about 0.1 microns to about 0.6 microns, up to about 0.1 microns to about 0.5 microns, up to about 0.1 microns to about 0.4 microns, up to about 0.1 microns to about 0.4 microns, up to about 0.1 microns to about 0.3 microns, or up to about 0.3 to about 0.2 microns, or up to about 0.3 microns to about 0.4 microns. 35. The method of any one of embodiments 1-34, wherein the aerosol comprises a condensate of a nicotine salt. 36. The method of any one of embodiments 1-34, wherein the aerosol comprises a condensate comprising one or more of a carrier, a nicotine salt, free base nicotine, and a free acid. 37. The method of any one of claims 1 to 9, wherein the acid does not decompose at room temperature and does not decompose at the operating temperature of the electronic cigarette. 38. The method according to any one of embodiments 1-37, wherein the operating temperature is from 150°C to 250°C. 39. The method of any one of embodiments 1-37, wherein the operating temperature is from 180°C to 220°C. 40. The method of any one of embodiments 1-37, wherein the operating temperature is about 200°C. 41. The method of any one of embodiments 1-40, wherein the acid is stable at or below the operating temperature of about 200° C. 42. The method of any one of embodiments 1-40, wherein the acid does not decompose at or below the operating temperature of about 200° C. 43. The method of any one of embodiments 1-40, wherein the acid does not oxidize at or below the operating temperature of about 200° C. 44. The method of any one of embodiments 1-43, wherein the formulation is non-toxic to users of the electronic cigarette. 45. The method of any one of embodiments 1-44, wherein the formulation is not corrosive to the electronic cigarette. 46. ​​The method of any one of embodiments 1-45, wherein the formulation comprises a flavoring agent. 47. The method of any one of embodiments 1-46, wherein inhalation of the aerosol for 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 1 minute to about 8 minutes. 48. Nicotine plasma Tmax from about 1 minute to about 7 minutes, from about 1 minute to about 6 minutes, from about 1 minute to about 5 minutes, from about 1 minute to about 4 minutes, from about 1 minute to about 3 minutes, from about 1 minute to about 2 minutes, from about 2 minutes to about 8 minutes, from about 2 minutes to about 7 minutes, from about 2 minutes to about 6 minutes, from about 2 minutes to about 5 minutes, from about 2 minutes to about 4 minutes, from about 2 minutes to about 3 minutes, from about 3 minutes to about 8 minutes, from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes 48. The method of embodiment 47, wherein the reaction time is from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. 49. The method of any one of embodiments 1-46, wherein inhalation of the aerosol for about 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 2 minutes to about 8 minutes. 50. Nicotine plasma Tmax is from about 2 minutes to about 8 minutes, from about 2 minutes to about 7 minutes, from about 2 minutes to about 6 minutes, from about 2 minutes to about 5 minutes, from about 2 minutes to about 4 minutes, from about 2 minutes to about 3 minutes, from about 3 minutes to about 8 minutes, from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, 50. The method of embodiment 49, wherein the reaction time is from 5 minutes to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, or about 2 minutes. 51. The method of any one of embodiments 1-46, wherein inhalation of the aerosol for about 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 3 minutes to about 8 minutes. 52. The method of embodiment 51, wherein the nicotine plasma Tmax is from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about 8 minutes, from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, or about 3 minutes. 53. The method of any one of embodiments 1-46, wherein Tmax is less than about 8 minutes. 54. The method according to any one of embodiments 47-53, wherein Tmax is determined based on at least three independent data sets. 55. The method of any one of embodiments 47-53, wherein Tmax is the range of at least three independent data sets. 56. The method of any one of embodiments 47-53, wherein Tmax is the mean ± standard deviation of at least three independent data sets. 57. The method of any one of embodiments 1-56, wherein the liquid carrier comprises glycerin, propylene glycol, trimethylene glycol, water, ethanol, or a combination thereof. 58. The method of any one of embodiments 1-56, wherein the liquid carrier comprises propylene glycol and vegetable glycerin. 59. The method of any one of embodiments 1-56, wherein the liquid carrier comprises 20% to 50% propylene glycol and 80% to 50% vegetable glycerin. 60. The method of any one of embodiments 1-56, wherein the liquid carrier comprises 30% propylene glycol and 70% vegetable glycerin. 61. The method of any one of embodiments 1-17, wherein the formulation further comprises one or more additional acids. 62. The method of embodiment 21, wherein the 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 of embodiment 21, wherein the one or more additional acids include benzoic acid. 64. The method of any one of embodiments 21-63, wherein the one or more additional acids form one or more additional nicotine salts. 65. A method of delivering nicotine to a user, comprising the steps of deploying a low-temperature electronic vaporization device, i.e., an e-cigarette, the e-cigarette comprising a nicotine formulation, the nicotine formulation comprising: a. from about 0.5% (w / w) to about 20% (w / w) nicotine; 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 acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 66. A method of delivering nicotine to a user, comprising the steps of deploying a low-temperature electronic vaporization device, i.e., an e-cigarette, the e-cigarette comprising a nicotine formulation, the nicotine formulation comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; 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 acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 67. A method of delivering nicotine to a user, comprising the steps of deploying a low-temperature electronic vaporization device, i.e., an e-cigarette, the e-cigarette comprising a nicotine formulation, the nicotine formulation comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; 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 acid to nicotine is from about 1:1 to about 2:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 68. A method of delivering nicotine to a user, comprising the steps of deploying a low-temperature electronic vaporization device, i.e., an e-cigarette, the e-cigarette comprising a nicotine formulation, the nicotine formulation comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; b. the molar ratio of benzoic acid to nicotine is about 1:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 69. A formulation for use in a low-temperature electronic vaporization device, i.e. an electronic cigarette, comprising: a. from about 0.5% (w / w) to about 20% (w / w) nicotine; b. the molar ratio of acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 70. The formulation described in embodiment 69, wherein 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 the acid and nicotine form a nicotine salt. 72. The formulation of embodiments 69-71, characterized in that it contains monoprotonated nicotine. 73. A formulation according to any one of embodiments 69-72, characterized in that the aerosol contains monoprotonated nicotine. 74. A formulation described in any one of embodiments 69-73, characterized in that the aerosol is delivered to the user's lungs. 75. The formulation described in embodiment 74, wherein 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 the aerosol. 77. A formulation according to any one of embodiments 69-75, characterized in that nicotine is delivered in salt form in the aerosol. 78. A formulation according to any one of embodiments 69-77, characterized in that the acid contains one carboxylic acid functional group. 79. A formulation according to any one of embodiments 69-77, characterized in that the acid contains more than one carboxylic acid functional group. 80. 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, saccharic acid, salicylic acid, sorbic acid, malic acid, or malic acid. 81. A formulation according to any one of embodiments 69-77, characterized in that the acid comprises one or more of a carboxylic acid, a dicarboxylic acid and a keto acid. 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 comprises 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 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. 85. A formulation according to any one of embodiments 69-83, wherein the molar ratio of acidic functional groups to nicotine in the formulation 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. 86. A formulation according to any one of embodiments 69-83, wherein the molar ratio of acidic functional group hydrogen to nicotine in the formulation 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. 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 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. 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 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. 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 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. 90. The nicotine concentration is 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), from about 0.5% (w / w) to about 10% (w / w), from about 0.5% (w / w) to about 8% (w / w), from about 0.5% (w / w) to about 7% (w / w), from about 0.5% (w / w) to about 6% (w / w), from about 0.5% (w / w) to about 5% (w / w), From about 0.5% (w / w) to about 4% (w / w), from about 0.5% (w / w) to about 3% (w / w), Alternatively, the formulation according to any one of embodiments 69-89 is from about 0.5% (w / w) to about 2% (w / w). 91. Nicotine concentration is about 0.5% (w / w), about 1% (w / w), about 2% (w / w), about 3% (w / w), about 4% (w / w), about 5% (w / w), about 6% (w / w), about 7% (w / w), The formulation according to any one of embodiments 69-89, characterized in that the solubility is about 8% (w / w), about 9% (w / w), about 10% (w / w), about 11% (w / w), about 12% (w / w), about 13% (w / w), about 14% (w / w), about 15% (w / w), about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), or about 20% (w / w). 92. The nicotine concentration is 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), from about 1% (w / w) to about 10% (w / w), from about 1% (w / w) to about 8% (w / w), from about 1% (w / w) to about 7% (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), Alternatively, the formulation according to any one of embodiments 69-89 is from about 1% (w / w) to about 2% (w / w). 93. The formulation according to any one of embodiments 69-89, characterized in that the nicotine concentration is 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). 94. The formulation according to any one of embodiments 69-89, characterized in that the nicotine concentration is 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). 95. The formulation according to any one of embodiments 69-89, characterized in that the nicotine concentration is 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). 96. A formulation according to any one of embodiments 69-89, characterized in that the nicotine concentration is 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). 97. A formulation according to any one of embodiments 69-89, characterized in that the nicotine concentration is from 6% (w / w) to about 20% (w / w), from about 6% (w / w) to about 18% (w / w), from about 6% (w / w) to about 15% (w / w), from about 6% (w / w) to about 12% (w / w), from about 6% (w / w) to about 10% (w / w), from about 6% (w / w) to about 8% (w / w), or from about 6% (w / w) to about 7% (w / w). 98. The formulation of any one of embodiments 69-89, wherein the nicotine concentration is from about 2% (w / w) to about 6% (w / w). 99. A formulation described in any one of embodiments 69-89, characterized in that the nicotine concentration is about 5% (w / w). 100. The formulation of any one of embodiments 69-99, wherein 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, wherein the aerosol comprises about 50% of the nicotine in the formulation, about 60% of the nicotine in the formulation, about 70% of the nicotine in the formulation, about 75% of the nicotine in the formulation, about 80% of the nicotine in the formulation, about 85% of the nicotine in the formulation, about 90% of the nicotine in the formulation, about 95% of the nicotine in the formulation, or about 99% of the nicotine in the formulation. 102. The aerosol may be from about 0.1 microns to about 5 microns, from about 0.1 microns to about 4.5 microns, from about 0.1 microns to about 4 microns, from about 0.1 microns to about 3.5 microns, from about 0.1 microns to about 3 microns, from about 0.1 microns to about 2.5 microns, from about 0.1 microns to about 2 microns, from about 0.1 microns to about 1.5 microns, from about 0.1 microns to about 1 micron, from about 0.1 microns to about 0.9 ... The formulation of any one of embodiments 69-101, characterized in that it comprises condensate in a particle size of from about 0.1 micron to about 0.8 microns, from about 0.1 micron to about 0.7 microns, from about 0.1 micron to about 0.6 microns, from about 0.1 micron to about 0.5 microns, from about 0.1 micron to about 0.4 microns, from about 0.1 micron to about 0.3 microns, from about 0.1 micron to about 0.2 microns, or from about 0.3 to about 0.4 microns. 103. A formulation according to any of embodiments 69-102, characterized in that the aerosol comprises 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 comprising one or more of a carrier, a nicotine salt, free base nicotine and free acid. 105. A formulation described in 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 the electronic cigarette. 106. A formulation described in any one of embodiments 69-105, characterized in that the operating temperature of the electronic cigarette is from 150°C to 250°C. 107. A formulation described in any one of embodiments 69-105, characterized in that the operating temperature of the electronic cigarette is from 180°C to 220°C. 108. A formulation described in any one of embodiments 69-105, characterized in that the operating temperature of the electronic cigarette is about 200°C. 109. A formulation described in any one of embodiments 69-108, characterized in that the acid is stable at the operating temperature of the electronic cigarette or at about 200°C and below. 110. A formulation described in any one of embodiments 69-108, characterized in that the acid does not decompose at the operating temperature of the electronic cigarette or at about 200°C and below. 111. A formulation described in any one of embodiments 69-108, characterized in that the acid does not oxidize at the operating temperature of the electronic cigarette or at about 200°C and below. 112. A formulation described in any one of embodiments 69-108, characterized in that the formulation is non-toxic to users of electronic cigarettes. 113. A formulation described in any one of embodiments 69-112, characterized in that the formulation does not corrode electronic cigarettes. 114. A formulation described in any one of embodiments 69-113, characterized in that the formulation comprises a flavoring agent. 115. A formulation according to any one of embodiments 69-114, characterized in that inhalation of the aerosol for 5 minutes at a rate of 1 inhalation per 30 seconds results in a nicotine plasma Tmax of from about 1 minute to about 8 minutes. 116. Nicotine plasma Tmax is from about 1 minute to about 7 minutes, from about 1 minute to about 6 minutes, from about 1 minute to about 5 minutes, from about 1 minute to about 4 minutes, from about 1 minute to about 3 minutes, from about 1 minute to about 2 minutes, from about 2 minutes to about 8 minutes, from about 2 minutes to about 7 minutes, from about 2 minutes to about 6 minutes, from about 2 minutes to about 5 minutes, from about 2 minutes to about 4 minutes, from about 2 minutes to about 3 minutes, from about 3 minutes to about 8 minutes, from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes 116. The formulation of embodiment 115, wherein the time period is from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. 117. The formulation of any one of embodiments 69-114, wherein inhalation of the aerosol for about 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 2 minutes to about 8 minutes. 118. Nicotine plasma Tmax is from about 2 minutes to about 8 minutes, from about 2 minutes to about 7 minutes, from about 2 minutes to about 6 minutes, from about 2 minutes to about 5 minutes, from about 2 minutes to about 4 minutes, from about 2 minutes to about 3 minutes, from about 3 minutes to about 8 minutes, from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 6 minutes, The formulation of embodiment 117, wherein the solubility is from about 5 to about 7 minutes, from about 5 to about 6 minutes, from about 6 to about 8 minutes, from about 6 to about 7 minutes, from about 7 to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, or about 2 minutes. 119. A formulation described in any one of embodiments 69-114, characterized in that inhalation of the aerosol for about 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 3 minutes to about 8 minutes. 120. The formulation of embodiment 119, wherein the nicotine plasma Tmax is from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about 8 minutes, from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, or about 3 minutes. 121. A formulation according to any one of embodiments 69-114, characterized in that the Tmax is less than about 8 minutes. 122. A formulation according to any one of embodiments 115-121, characterized in that Tmax is determined based on at least three independent data sets. 123. The formulation described in embodiments 115-121, characterized in that Tmax is in the range of at least three independent data sets. 124. The formulation described in embodiments 115-121, wherein Tmax is the mean ± standard deviation of at least three independent data sets. 125. A formulation described in 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. A formulation described in any one of embodiments 69-124, characterized in that the liquid carrier comprises propylene glycol and vegetable glycerin. 127. A formulation described in any one of embodiments 69-124, characterized in that the liquid carrier comprises 20% to 50% propylene glycol and 80% to 50% vegetable glycerin. 128. A formulation described in any one of embodiments 69-114, characterized in that the liquid carrier comprises 30% propylene glycol and 70% vegetable glycerin. 129. A formulation according to any one of embodiments 69-128, characterized in that the formulation further comprises one or more additional acids. 130. The formulation of embodiment 129, wherein the 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. 131. The formulation described in embodiment 129, wherein the one or more additional acids include benzoic acid. 132. The formulation of any one of embodiments 129-131, wherein the one or more additional acids form one or more additional nicotine salts. 133. A formulation for use in a low-temperature electronic vaporization device, i.e. an electronic cigarette, comprising: a. from about 0.5% (w / w) to about 20% (w / w) nicotine; 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 acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol comprising at least a portion of the nicotine in the formulation. 134. A formulation for use in a low-temperature electronic vaporization device, i.e. an electronic cigarette, comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; 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 acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol comprising at least a portion of the nicotine in the formulation. 135. A formulation for use in a low-temperature electronic vaporization device, i.e. an electronic cigarette, comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; 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 acid to nicotine is from about 1:1 to about 2:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol comprising at least a portion of the nicotine in the formulation. 136. A formulation for use in a low-temperature electronic vaporization device, i.e. an electronic cigarette, comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; b. the molar ratio of benzoic acid to nicotine is about 1:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol comprising at least a portion of the nicotine in the formulation. 137. A cartridge for use in a low-temperature electronic vaporization device, i.e., an electronic cigarette, the cartridge including a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment including a nicotine formulation, the nicotine formulation comprising: a. from about 0.5% (w / w) to about 20% (w / w) nicotine; b. the molar ratio of acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 138. The cartridge of embodiment 137, wherein the molar ratio of acidic functional groups to nicotine is from about 1:1 to about 4:1. 139. The cartridge of any one of embodiments 137138, wherein the acid and nicotine form a nicotine salt. 140. The cartridge of any one of embodiments 137-139, comprising 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, wherein the aerosol is delivered to the lungs of the user. 143. The cartridge of embodiment 142, wherein the aerosol is delivered to the alveoli in the user's lungs. 144. The cartridge according to any one of embodiments 137-143, characterized in that the nicotine is stable in salt form in the aerosol. 145. A cartridge according to any one of embodiments 137-143, characterized in that the nicotine is delivered in salt form in the aerosol. 146. The cartridge of any one of embodiments 137-145, wherein the acid contains one carboxylic acid functional group. 147. The cartridge of any one of embodiments 137-143, wherein the acid contains more than one carboxylic acid functional group. 148. The 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, malic acid, or malic acid. 149. The cartridge of any one of embodiments 137-145, wherein the acid comprises one or more of a carboxylic acid, a dicarboxylic acid, and a keto acid. 150. The cartridge of any one of embodiments 137-145, wherein the acid comprises one or more of benzoic acid, pyruvic acid, salicylic acid, levulinic acid, malic acid, succinic acid, and citric acid. 151. The cartridge of any one of embodiments 137-145, wherein the acid comprises 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 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. 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 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. 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 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. 155. A cartridge according to any one of embodiments 137-151, wherein the molar ratio of acid 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. 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 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. 157. 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 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. 158. Nicotine concentration is about 0.5% (w / w), about 1% (w / w), about 2% (w / w), about 3% (w / w), about 4% (w / w), about 5% (w / w), about 6% (w / w), about 7% (w / w), The cartridge of any one of embodiments 137-157, characterized in that the ionic liquid is about 8% (w / w), about 9% (w / w), about 10% (w / w), about 11% (w / w), about 12% (w / w), about 13% (w / w), about 14% (w / w), about 15% (w / w), about 16% (w / w), about 17% (w / w), about 18% (w / w), about 19% (w / w), or about 20% (w / w). 159. The nicotine concentration is 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), from about 0.5% (w / w) to about 10% (w / w), from about 0.5% (w / w) to about 8% (w / w), from about 0.5% (w / w) to about 7% (w / w), from about 0.5% (w / w) to about 6% (w / w), from about 0.5% (w / w) to about 5% (w / w), from about 0.5% (w / w) to about 4% (w / w), from about 0.5% (w / w) to about 3% (w / w), or from about 0.5% (w / w) to about 2% (w / w). 160. The nicotine concentration is 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), from about 1% (w / w) to about 10% (w / w), from about 1% (w / w) to about 8% (w / w), from about 1% (w / w) to about 7% (w / w), The cartridge according to any one of embodiments 137-157, characterized in that the concentration of the cellulose acetate hydrochloride in the composition is 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). 161. The formulation according to any one of embodiments 137-157, characterized in that the nicotine concentration is 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). 162. The cartridge of any one of embodiments 137-157, characterized in that the nicotine concentration is 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). 163. The cartridge of any one of embodiments 137-157, characterized in that the nicotine concentration is 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). 164. A cartridge according to any one of embodiments 137-157, characterized in that the nicotine concentration is 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). 165. A cartridge according to any one of embodiments 137-157, characterized in that the nicotine concentration is from 6% (w / w) to about 20% (w / w), from about 6% (w / w) to about 18% (w / w), from about 6% (w / w) to about 15% (w / w), from about 6% (w / w) to about 12% (w / w), from about 6% (w / w) to about 10% (w / w), from about 6% (w / w) to about 8% (w / w), or from about 6% (w / w) to about 7% (w / w). 166. The cartridge of any one of embodiments 137-157, wherein the nicotine concentration is from about 2% (w / w) to about 6% (w / w). 167. A cartridge according to any one of embodiments 137-157, characterized in that the nicotine concentration is about 5% (w / w). 168. The cartridge of any one of embodiments 137-157, wherein 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 comprises about 50% of the nicotine in the formulation, about 60% of the nicotine in the formulation, about 70% of the nicotine in the formulation, about 75% of the nicotine in the formulation, about 80% of the nicotine in the formulation, about 85% of the nicotine in the formulation, about 90% of the nicotine in the formulation, about 95% of the nicotine in the formulation, or about 99% of the nicotine in the formulation. 170. The aerosol may be from about 0.1 microns to about 5 microns, from about 0.1 microns to about 4.5 microns, from about 0.1 microns to about 4 microns, from about 0.1 microns to about 3.5 microns, from about 0.1 microns to about 3 microns, from about 0.1 microns to about 2.5 microns, from about 0.1 microns to about 2 microns, from about 0.1 microns to about 1.5 microns, from about 0.1 microns to about 1 micron, from about 0.1 microns to about 0.9 microns, from about 0.1 The cartridge of any one of embodiments 137-169, comprising condensate in a particle size of from 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. The cartridge of any of embodiments 137-170, wherein the aerosol comprises a condensate of a nicotine salt. 172. The cartridge of any one of embodiments 137-170, wherein the aerosol comprises a condensate comprising 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 electronic cigarette. 174. A cartridge according to any one of embodiments 137-173, characterized in that the operating temperature of the electronic cigarette is from 150°C to 250°C. 175. A formulation described in any one of embodiments 69-105, characterized in that the operating temperature of the electronic cigarette is from 180°C to 220°C. 176. A cartridge described in any one of embodiments 137-173, characterized in that the operating temperature of the electronic cigarette is about 200°C. 177. A cartridge according to any one of embodiments 137-176, wherein the acid is stable at the operating temperature of the electronic 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 electronic cigarette or at about 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 electronic cigarette or at about 200° C. and below. 180. A cartridge according to any one of embodiments 137-179, characterized in that the formulation is non-toxic to users of the electronic cigarette. 181. A cartridge according to any one of embodiments 137-180, characterized in that the formulation is not corrosive to the electronic cigarette. 182. A cartridge according to any one of embodiments 137-181, wherein the formulation comprises a flavoring agent. 183. A cartridge according to any one of embodiments 137-182, characterized in that inhalation of the aerosol for 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 1 minute to about 8 minutes. 184. Nicotine plasma Tmax is from about 1 minute to about 7 minutes, from about 1 minute to about 6 minutes, from about 1 minute to about 5 minutes, from about 1 minute to about 4 minutes, from about 1 minute to about 3 minutes, from about 1 minute to about 2 minutes, from about 2 minutes to about 8 minutes, from about 2 minutes to about 7 minutes, from about 2 minutes to about 6 minutes, from about 2 minutes to about 5 minutes, from about 2 minutes to about 4 minutes, from about 2 minutes to about 3 minutes, from about 3 minutes to about 8 minutes, from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about The cartridge of embodiment 183, wherein the cartridge duration is up to about 7 minutes, about 4 to about 6 minutes, about 4 to about 5 minutes, about 5 to about 8 minutes, about 5 to about 7 minutes, about 5 to about 6 minutes, about 6 to about 8 minutes, about 6 to about 7 minutes, about 7 to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. 185. The cartridge of any one of embodiments 137-182, characterized in that inhalation of the aerosol for about 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 2 minutes to about 8 minutes. 186. Nicotine plasma Tmax is from about 2 minutes to about 8 minutes, from about 2 minutes to about 7 minutes, from about 2 minutes to about 6 minutes, from about 2 minutes to about 5 minutes, from about 2 minutes to about 4 minutes, from about 2 minutes to about 3 minutes, from about 3 minutes to about 8 minutes, from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 186. The cartridge of embodiment 185, wherein the time is from about to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, or about 2 minutes. 187. A cartridge according to any one of embodiments 137-182, characterized in that inhalation of the aerosol for about 5 minutes at a rate of 1 inhalation every 30 seconds results in a nicotine plasma Tmax of from about 3 minutes to about 8 minutes. 188. The cartridge of embodiment 187, wherein the nicotine plasma Tmax is from about 3 minutes to about 7 minutes, from about 3 minutes to about 6 minutes, from about 3 minutes to about 5 minutes, from about 3 minutes to about 4 minutes, from about 4 minutes to about 8 minutes, from about 4 minutes to about 7 minutes, from about 4 minutes to about 6 minutes, from about 4 minutes to about 5 minutes, from about 5 minutes to about 8 minutes, from about 5 minutes to about 7 minutes, from about 5 minutes to about 6 minutes, from about 6 minutes to about 8 minutes, from about 6 minutes to about 7 minutes, from about 7 minutes to about 8 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, or about 3 minutes. 189. A cartridge described in any one of embodiments 137-182, characterized in that Tmax is less than about 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 data sets. 191. The cartridge described in embodiments 183-189, characterized in that Tmax is the range of at least three independent data sets. 192. The cartridge described in embodiments 183-189, wherein Tmax is the mean ± standard deviation of at least three independent data sets. 193. The cartridge of any one of embodiments 137-192, wherein 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 comprises propylene glycol and vegetable glycerin. 195. A cartridge according to any one of embodiments 137-192, characterized in that the liquid carrier comprises 20% to 50% propylene glycol and 80% to 50% vegetable glycerin. 196. A cartridge according to any one of embodiments 137-192, wherein the liquid carrier comprises 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 of embodiment 197, wherein the 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. 199. The cartridge of embodiment 197, wherein the one or more additional acids include benzoic acid. 200. The cartridge of any one of embodiments 197-199, wherein the one or more additional acids form one or more additional nicotine salts. 201. A cartridge for use in a low-temperature electronic vaporization device, i.e., an electronic cigarette, the cartridge including a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment including a nicotine formulation, the nicotine formulation comprising: a. from about 0.5% (w / w) to about 20% (w / w) nicotine 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 acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 202. A cartridge for use in a low-temperature electronic vaporization device, i.e., an electronic cigarette, the cartridge including a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment including a nicotine formulation, the nicotine formulation comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; 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 acid to nicotine is from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 203. A cartridge for use in a low-temperature electronic vaporization device, i.e., an electronic cigarette, the cartridge including a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment including a nicotine formulation, the nicotine formulation comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; 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 acid to nicotine is from about 1:1 to about 2:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation. 204. A cartridge for use in a low-temperature electronic vaporization device, i.e., an electronic cigarette, the cartridge including a fluid compartment configured to be in fluid communication with a heating element, the fluid compartment including a nicotine formulation, the nicotine formulation comprising: a. from about 2% (w / w) to about 6% (w / w) nicotine; b. the molar ratio of benzoic acid to nicotine is about 1:1; and c. a biologically acceptable liquid carrier, wherein actuation of the electronic cigarette produces an inhalable aerosol containing at least a portion of the nicotine in the formulation.

[0134] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous modifications, changes, and substitutions will occur to those skilled in the art without departing from the invention. It will be understood that various alternatives to the embodiments of the invention described herein may be used in practicing the invention. It is intended that the following embodiments define the scope of the invention, and that methods and structures within the scope of such embodiments and their equivalents are covered thereby.

Claims

1. 1. A method for generating an inhalable aerosol comprising nicotine for delivery to a user, the method comprising: using a low-temperature electronic vaporization device, i.e., an e-cigarette, comprising a nicotine liquid formulation and a heater, the nicotine liquid formulation comprising nicotine, an acid and a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The method of claim 1, wherein the heater heats a quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the quantity is in the aerosol, and wherein at least about 90% of the nicotine in the quantity is in the aerosol.

2. 2. The method of claim 1, wherein the amount comprises about 4 μL of the nicotine liquid formulation.

3. 2. The method of claim 1, wherein the amount comprises about 4.5 mg of the nicotine liquid formulation.

4. 4. The method of claim 1, wherein the concentration of nicotine is from about 0.5% (w / w) to about 20% (w / w).

5. 5. The method of claim 1, wherein the molar ratio of the acid to the nicotine is from about 0.25:1 to about 4:

1.

6. 6. The method of claim 1, wherein the acid comprises one or more acidic functional groups, and the molar ratio of acidic functional groups to nicotine is from about 0.25:1 to about 4:

1.

7. 7. The method of claim 1, wherein the acid and the nicotine form a nicotine salt.

8. 8. The method of claim 7, wherein the nicotine is stabilized in a nicotine salt in the inhalable aerosol.

9. 8. The method of claim 7, wherein the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier, and the nicotine salt.

10. 10. The method of claim 1, wherein one or more particles of the inhalable aerosol are sized for delivery to the lungs of the user.

11. 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. 11. The method according to claim 1, wherein the acid is selected from the group consisting of benzoic acid, pyruvic acid and salicylic acid.

13. 11. The method according to claim 1, wherein the acid is benzoic acid.

14. 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. 14. The method according to claim 1, wherein said concentration is about 5% (w / w).

16. 16. The method of any one of claims 1 to 15, wherein the biologically acceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin.

17. 16. The method of any one of claims 1 to 15, wherein the biologically acceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.

18. 18. The method of any one of claims 1 to 17, wherein the heater heats the amount of the nicotine liquid formulation to about 150°C to about 250°C.

19. 18. The method of any one of claims 1 to 17, wherein the heater heats the amount of the nicotine liquid formulation to about 180°C to about 220°C.

20. 18. The method of any one of claims 1 to 17, wherein the heater heats the amount of the nicotine liquid formulation to about 200°C.

21. 21. The method of any one of claims 1 to 20, wherein 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.

22. 22. The method of claim 21, wherein the additional acid forms an additional nicotine salt.

23. 23. The method of any one of claims 1 to 22, wherein at least about 60% to about 90% of said amount of acid is in said aerosol.

24. 23. The method of any one of claims 1 to 22, wherein at least about 70% to about 90% of said amount of acid is in said aerosol.

25. 23. The method of any one of claims 1 to 22, wherein at least about 80% to about 90% of said amount of said acid is in said aerosol.

26. 23. The method of any one of claims 1 to 22, wherein greater than about 90% of said amount of acid is in said aerosol.

27. 1. A method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising: The method includes using a low-temperature electronic vaporization device, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, Nicotine liquid preparations are a. nicotine in a concentration from about 0.5% (w / w) to about 20% (w / w); b. an acid having a molar ratio to said nicotine of from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The method of claim 1, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the quantity is in the aerosol, and wherein about 90% of the nicotine in the quantity is in the aerosol.

28. 1. A method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising: The method includes using a low-temperature electronic vaporization device, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, Nicotine liquid preparations are a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. an acid having a molar ratio to nicotine of from about 1:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The method of claim 1, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the quantity is in the aerosol, and wherein about 90% of the nicotine in the quantity is in the aerosol.

29. 1. A method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising: The method includes using a low-temperature electronic vaporization device, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, Nicotine liquid preparations are a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. an acid having a molar ratio to nicotine of from about 1:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The method, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the acid in the quantity is in the aerosol, and wherein about 90% of the nicotine in the quantity is in the aerosol.

30. 1. A method of generating an inhalable aerosol comprising nicotine for delivery to a user, comprising: The method includes using a low-temperature electronic vaporization device, i.e., an e-cigarette, which includes a nicotine liquid formulation and a heater, Nicotine liquid preparations are a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. benzoic acid in a molar ratio to said nicotine of about 1:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The method, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the benzoic acid in the quantity is in the aerosol, and wherein about 90% of the nicotine in the quantity is in the aerosol.

31. 1. A cartridge for use in a low temperature electronic vaporization device, i.e., an electronic cigarette, comprising: The cartridge includes a fluid compartment configured to be in fluid communication with a heating element; the fluid compartment comprises a nicotine formulation comprising said nicotine, an acid and a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The cartridge, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, such that at least about 50% of the acid in the quantity is in the aerosol, and such that about 90% of the nicotine in the quantity is in the aerosol.

32. 32. The cartridge of claim 31, wherein the amount comprises about 4 μL of the nicotine liquid formulation.

33. 32. The cartridge of claim 31, wherein the amount comprises about 4.5 mg of the nicotine liquid formulation.

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

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

1.

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

1.

37. 37. A cartridge according to any one of claims 31 to 36, wherein the acid and the nicotine form a nicotine salt.

38. 38. The cartridge of claim 37, wherein the nicotine is stabilized in a nicotine salt in the inhalable aerosol.

39. 38. A cartridge as claimed in claim 37, wherein the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier and the nicotine salt.

40. 40. A cartridge according to any one of claims 31 to 39, wherein one or more particles of the inhalable aerosol are sized for delivery to the lungs of the user.

41. 41. A 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. 41. A 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. 41. A cartridge according to any one of claims 31 to 40, characterised in that the acid is benzoic acid.

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

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

46. 46. ​​The cartridge of any one of claims 31 to 45, wherein the biologically acceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin.

47. 46. ​​The cartridge of any one of claims 31 to 45, wherein the biologically acceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.

48. 48. A cartridge according to any one of claims 31 to 47, wherein the heater heats the quantity of the nicotine liquid formulation to about 150°C to about 250°C.

49. 48. A cartridge according to any one of claims 31 to 47, wherein the heater heats the quantity of the nicotine liquid formulation to about 180°C to about 220°C.

50. 48. A cartridge according to any one of claims 31 to 47, wherein the heater heats the quantity of the nicotine liquid formulation to approximately 200°C.

51. 51. A cartridge according to any one of claims 31 to 50, wherein 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.

52. 52. A cartridge as described in claim 51, characterized in that the additional acid forms an additional nicotine salt.

53. A cartridge according to any one of claims 31 to 52, wherein at least about 60% to about 90% of said amount of acid is in said aerosol.

54. 53. A cartridge according to any one of claims 31 to 52, wherein at least about 70% to about 90% of said amount of acid is in said aerosol.

55. 53. A cartridge according to any one of claims 31 to 52, wherein at least about 80% to about 90% of said amount of acid is in said aerosol.

56. 53. A cartridge according to any one of claims 31 to 52, wherein greater than about 90% of said amount of acid is in said aerosol.

57. 1. A cartridge for use in a low temperature electronic vaporization device, i.e., an electronic cigarette, comprising: The cartridge includes a fluid compartment configured to be in fluid communication with a heating element; the fluid compartment comprises a nicotine liquid formulation; The nicotine liquid formulation comprises: a. nicotine in a concentration from about 0.5% (w / w) to about 20% (w / w); b. an acid having a molar ratio to nicotine of from about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The cartridge, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, such that at least about 50% of the acid in the quantity is in the aerosol, and such that about 90% of the nicotine in the quantity is in the aerosol.

58. 1. A cartridge for use in a low temperature electronic vaporization device, i.e., an electronic cigarette, comprising: The cartridge includes a fluid compartment configured to be in fluid communication with a heating element; the fluid compartment comprises a nicotine liquid formulation; The nicotine liquid formulation comprises: a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. an acid having a molar ratio to nicotine of from about 1:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The cartridge, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, such that at least about 50% of the acid in the quantity is in the aerosol, and such that about 90% of the nicotine in the quantity is in the aerosol.

59. 1. A cartridge for use in a low temperature electronic vaporization device, i.e., an electronic cigarette, comprising: The cartridge includes a fluid compartment configured to be in fluid communication with a heating element; the fluid compartment comprises a nicotine liquid formulation; The nicotine liquid formulation comprises: a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. an acid having a molar ratio to nicotine of from about 1:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the acid in the quantity is in the aerosol, and about 90% of the nicotine in the quantity is in the aerosol.

60. 1. A cartridge for use in a low temperature electronic vaporization device, i.e., an electronic cigarette, comprising: The cartridge includes a fluid compartment configured to be in fluid communication with a heating element; the fluid compartment comprises a nicotine liquid formulation; The nicotine liquid formulation comprises: a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. Benzoic acid in a molar ratio to nicotine of about 1:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The cartridge, wherein the heater heats the quantity of the nicotine liquid formulation to form an aerosol, and at least about 90% of the benzoic acid in the quantity is in the aerosol, and about 90% of the nicotine in the quantity is in the aerosol.

61. A formulation for use in a low temperature electronic vaporization device, i.e. an electronic cigarette, comprising a heater, comprising: The formulation comprises nicotine, an acid and a biologically acceptable liquid carrier; Using an electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; the heater heats the amount of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the amount is in the aerosol, and A formulation, wherein about 90% of said nicotine is in said aerosol.

62. 62. The formulation of claim 61, wherein the amount comprises about 4 μL of the nicotine liquid formulation.

63. 62. The formulation of claim 61, wherein the amount comprises about 4.5 mg of the nicotine liquid formulation.

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

1.

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

1.

67. 67. A formulation according to any one of claims 61 to 66, wherein the acid and the nicotine form a nicotine salt.

68. 68. The formulation of claim 67, wherein the nicotine is stable in a nicotine salt in the inhalable aerosol.

69. 68. The formulation of claim 67, wherein the inhalable aerosol comprises one or more of the nicotine, the acid, the carrier and the nicotine salt.

70. 70. The formulation of any one of claims 61 to 69, wherein one or more particles of the inhalable aerosol are sized for delivery to the lungs of the user.

71. 71. A 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. 71. A 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. 71. A formulation according to any one of claims 61 to 70, characterized in that the acid is benzoic acid.

74. 74. A 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. 74. A formulation according to any one of claims 61 to 73, characterized in that the concentration is about 5% (w / w).

76. 76. The formulation of any one of claims 61 to 75, wherein the biologically acceptable liquid carrier comprises about 20% to about 50% propylene glycol and about 80% to about 50% vegetable glycerin.

77. 76. The formulation of any one of claims 61 to 75, wherein the biologically acceptable liquid carrier comprises about 30% propylene glycol and about 70% vegetable glycerin.

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

79. 78. The formulation of any one of claims 61 to 77, wherein the heater heats the amount of the nicotine liquid formulation to about 180°C to about 220°C.

80. 78. The formulation of any one of claims 61 to 77, wherein the heater heats the amount of the nicotine liquid formulation to about 200°C.

81. 81. The nicotine liquid formulation of 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. 82. The formulation of claim 81, wherein the additional acid forms an additional nicotine salt.

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

84. 83. The formulation of any one of claims 61 to 82, wherein at least about 70% to about 90% of the amount of acid is in the aerosol.

85. 83. The formulation of any one of claims 61 to 82, wherein at least about 80% to about 90% of the amount of acid is in the aerosol.

86. 83. The formulation of any one of claims 61 to 82, wherein greater than about 90% of the amount of acid is in the aerosol.

87. A formulation for use in a low temperature electronic vaporization device, i.e. an electronic cigarette, comprising a heater, the formulation comprising: a. nicotine in a concentration from about 0.5% (w / w) to about 20% (w / w); b. an acid having a molar ratio of acid to nicotine of about 0.25:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the quantity is in the aerosol and about 90% of the nicotine in the quantity is in the aerosol.

88. A formulation for use in a low temperature electronic vaporization device, i.e. an electronic cigarette, comprising a heater, the formulation comprising: a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. an acid having a molar ratio of acid to nicotine of about 1:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 50% of the acid in the quantity is in the aerosol and about 90% of the nicotine in the quantity is in the aerosol.

89. A formulation for use in a low temperature electronic vaporization device, i.e. an electronic cigarette, comprising a heater, the formulation comprising: a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. an acid having a molar ratio of acid to nicotine of about 1:1 to about 4:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the acid in the quantity is in the aerosol, and about 90% of the nicotine in the quantity is in the aerosol.

90. A formulation for use in a low temperature electronic vaporization device, i.e. an electronic cigarette, comprising a heater, the formulation comprising: a. nicotine in a concentration from about 2% (w / w) to about 6% (w / w); b. benzoic acid, wherein the molar ratio of benzoic acid to nicotine is about 1:1; and c. a biologically acceptable liquid carrier; Using the electronic cigarette includes providing an amount of the nicotine liquid formulation to the heater; The heater heats the quantity of the nicotine liquid formulation to form an aerosol, wherein at least about 90% of the benzoic acid in the quantity is in the aerosol, and about 90% of the nicotine in the quantity is in the aerosol.

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