Gels and crystalline powders

Abstract

A gel is provided that includes (i) water in an amount of 1-20 wt.% based on the gel, (ii) nicotine, and (iii) a water-soluble acid. Further provided is a crystalline powder that includes (i) water in an amount of less than 15 wt.% based on the crystalline powder, (ii) nicotine, (iii) a water-soluble acid, (iv) one or more flavorings, and (v) an encapsulating material.

Description

Field of the Invention

[0001] The present disclosure relates to gels and crystalline powders, methods for producing gels and crystalline powders, containers containing gels and crystalline powders, devices containing gels and crystalline powders, and methods and uses of gels and crystalline powders. Background of the Invention

[0002] Electronic aerosol supply systems, such as e-cigarettes, generally include a reservoir of a liquid to be vaporized that typically contains nicotine. When the user inhales on the device, the heater operates to vaporize a small amount of the liquid, and thus the vaporized liquid is inhaled by the user.

[0003] The use of e-cigarettes in the UK has increased rapidly and it is now estimated that over a million people in the UK use e-cigarettes.

[0004] One challenge in providing such systems is supplying inhaled aerosols from an aerosol dispensing device that provide consumers with an acceptable experience. Some consumers may prefer e-cigarettes that produce aerosols that closely resemble the smoke inhaled from tobacco products such as cigarettes. Aerosols from e-cigarettes and smoke from tobacco products such as cigarettes result in a complex chain of flavors in the mouth, nicotine absorption in the mouth and throat, and subsequently nicotine absorption in the lungs. These various aspects are described by users in terms of flavor, intensity / quality, impact, irritation / smoothness, and nicotine reward. Nicotine contributes to several of these factors and is strongly related to factors such as impact, irritation, and smoothness, which are easily perceived by consumers, and e-cigarettes may give consumers too much or too little of these parameters, depending on individual preferences. Nicotine reward is particularly complex because it results from both the amount and rate of nicotine absorbed through the oral mucosa (typically vapor phase nicotine) and the amount and rate of nicotine absorbed through the lungs (typically particulate phase nicotine in the inhaled aerosol). Each of these factors, and the balance between them, can strongly contribute to the consumer acceptability of e-cigarettes. Therefore, providing means to optimize the overall vaping experience is desirable for e-cigarette manufacturers. [Overview of the project]

[0005] In one way, (i) Based on the gel, add 1-20 wt.% of water, (ii) Nicotine and, (iii) Water-soluble acids and A gel containing the following is provided.

[0006] In one way, (i) Based on the crystalline powder, add less than 15 wt.% of water, (ii) Nicotine and, (iii) A water-soluble acid, (iv) One or more fragrances, (v) Encapsulation material and A crystalline powder containing the above is provided.

[0007] In one way, (i) Based on the gel, add 1-20 wt.% of water, (ii) Nicotine and, (iii) Water-soluble acids and A method for producing a gel containing, (a) (i) 50-90 wt.% of water based on the nicotine solution, (ii) Nicotine, and (iii) Water-soluble acid The steps include preparing a nicotine solution containing, (b) The step of dehydrating the nicotine solution to obtain a gel A method is provided that includes this.

[0008] In one way, (i) Based on the crystalline powder, add less than 15 wt% of water, (ii) Nicotine and, (iii) A water-soluble acid, (iv) One or more fragrances, (v) Encapsulation material and A method for producing a crystalline powder containing, (a) (i) Based on the nicotine solution, add 50-95 wt.% of water, (ii) Nicotine and, (iii) A water-soluble acid, (iv) One or more fragrances, (v) Encapsulation material and The steps include preparing a nicotine solution containing, (b) The step of dehydrating the nicotine solution to obtain a crystalline powder. A method is provided that includes this.

[0009] In one way, (i) Based on the gel, a quantity of water of 1-20 wt.% (ii) Nicotine, and (iii) Water-soluble acid A method for rehydrating a gel comprising a step of contacting the gel with water is provided.

[0010] In one embodiment, (i) water in an amount less than 15 wt.% based on the crystalline powder, (ii) nicotine, (iii) a water-soluble acid, (iv) one or more flavorings, and (v) an encapsulating material A method for rehydrating a crystalline powder comprising a step of contacting the crystalline powder with water is provided.

[0011] In one embodiment, (a) a container, and (b) (i) water in an amount of 1 to 20 wt.% based on the gel, (ii) nicotine, and (iii) a water-soluble acid A contained gel comprising is provided.

[0012] In one embodiment, (a) a container, and (b) (i) water in an amount less than 15 wt.% based on the crystalline powder, (ii) nicotine, (iii) a water-soluble acid, (iv) one or more flavorings, and (v) an encapsulating material A contained crystalline powder comprising is provided. Detailed description

[0013] As discussed in one embodiment herein, in one embodiment, a gel is provided comprising (i) 1 to 20 wt.% of water based on the gel, (ii) nicotine, and (iii) a water-soluble acid. In a further embodiment, a crystalline powder is provided comprising (i) less than 15 wt.% of water based on the crystalline powder, (ii) nicotine, (iii) a water-soluble acid, (iv) one or more flavorings, and (v) an encapsulation material.

[0014] The inventors have found that they can provide a favorable system in which a gel is produced from nicotine and a water-soluble acid, and that this gel can be used in the production of a crystalline powder comprising water, nicotine, a water-soluble acid, one or more flavorings, and an encapsulating material. The gel is produced by producing a gel from a solution of nicotine, water, and a water-soluble acid, followed by dehydration of this solution. The gel is easily transported without the need to transport unnecessary amounts of water. The gel is also easy to handle and avoids the leakage problems associated with liquids. If necessary, the gel can then be used to produce a solution of water, nicotine, a water-soluble acid, one or more flavorings, and an encapsulating material. This is achieved by contacting the gel with water, one or more flavorings, and an encapsulating material. This method is further advantageous because the gel can be easily dissolved without heating. This avoids the loss of volatile nicotine and / or flavorings. This further solution can be dehydrated to produce a crystalline powder. This crystalline powder contains the components necessary to produce an aerosolizable liquid. The production of this liquid may be carried out by the manufacturer or the end user. The inventors have found that crystalline powders are particularly advantageous because they dissolve only when a sufficient amount of water is provided, and therefore any solution delivered will not be overly concentrated with respect to nicotine. This is important to ensure that an undesirably concentrated nicotine solution is not provided to the end user.

[0015] For ease of reference, these and further aspects of the invention are discussed here under appropriate section headings. However, the teachings in each section are not necessarily limited to each specific section.

[0016] As those skilled in the art will understand, nicotine may exist in a non-protonated, monoprotonated, or diprotonated form. The structures of each of these forms are shown below. [ka]

[0017] In this specification, the term "protonated form" refers to both monoprotonated and diprotonated nicotine. In this specification, the term "amount of protonated form" refers to the combined amount of monoprotonated and diprotonated nicotine. Furthermore, when referring to a fully protonated formulation, it will be understood that at any point, a very small amount of unprotonated nicotine may be present, e.g., less than 1% unprotonated nicotine.

[0018] water As discussed herein, the gel contains an amount of water of 1 to 20 wt.% based on the gel. In one embodiment, the water is present in an amount of 1 to 20 wt.% based on the gel. In one embodiment, the water is present in an amount of 1 to 15 wt.% based on the gel. In one embodiment, the water is present in an amount of 1 to 10 wt.% based on the gel.

[0019] As discussed herein, the crystalline powder contains less than 15 wt.% of water based on the crystalline powder. In one embodiment, the water is present in less than 10 wt.% of the crystalline powder. In one embodiment, the water is present in less than 8 wt.% of the crystalline powder.

[0020] nicotine It is possible to provide nicotine formulations that have desirable characteristics of flavor, impact, stimulation, smoothness, and / or nicotine reward for the user.

[0021] In one embodiment, nicotine is present in an amount of 6 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 10 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 10 wt% based on the total weight of the crystalline powder.

[0022] In one embodiment, nicotine is present in an amount of 8 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 8 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 8 wt% based on the total weight of the crystalline powder.

[0023] In one embodiment, nicotine is present in an amount of 6 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 6 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 6 wt% based on the total weight of the crystalline powder.

[0024] In one embodiment, nicotine is present in an amount of 5 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 5 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 5 wt% based on the total weight of the crystalline powder.

[0025] In one embodiment, nicotine is present in an amount of 4 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 4 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 4 wt% based on the total weight of the crystalline powder.

[0026] In one embodiment, nicotine is present in an amount of 3 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 3 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 3 wt% based on the total weight of the crystalline powder.

[0027] In one embodiment, nicotine is present in an amount of 2 wt% or less based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.01 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.02 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.05 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.08 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.1 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.2 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 0.5 to 2 wt% based on the total weight of the crystalline powder. In one embodiment, nicotine is present in an amount of 1 to 2 wt% based on the total weight of the crystalline powder.

[0028] In one embodiment, nicotine is present in an amount of 90 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45-90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 50-90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 60-90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 70-90 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 80-90 wt% based on the total weight of the gel.

[0029] In one embodiment, nicotine is present in an amount of 85 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 85 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45–85 wt% based on the total weight of the gel. In another embodiment, nicotine is present in an amount of 50–85 wt% based on the total weight of the gel.

[0030] In one embodiment, nicotine is present in an amount of 80 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45-80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 50-80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 60-80 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 70-80 wt% based on the total weight of the gel.

[0031] In one embodiment, nicotine is present in an amount of 75 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 75 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45–75 wt% based on the total weight of the gel. In another embodiment, nicotine is present in an amount of 50–75 wt% based on the total weight of the gel.

[0032] In one embodiment, nicotine is present in an amount of 70 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45-70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 50-70 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 60-70 wt% based on the total weight of the gel.

[0033] In one embodiment, nicotine is present in an amount of 60 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 60 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45–60 wt% based on the total weight of the gel. In another embodiment, nicotine is present in an amount of 50–60 wt% based on the total weight of the gel.

[0034] In one embodiment, nicotine is present in an amount of 50 wt% or less based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 1 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 5 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 10 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 15 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 20 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 25 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 30 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 35 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 40 to 50 wt% based on the total weight of the gel. In one embodiment, nicotine is present in an amount of 45-50 wt% based on the total weight of the gel.

[0035] The gel or crystalline powder contains nicotine in a protonated form. The gel or crystalline powder may also contain nicotine in an unprotonated form. In one embodiment, the gel or crystalline powder contains nicotine in an unprotonated form and nicotine in a monoprotonated form. In one embodiment, the gel or crystalline powder contains nicotine in an unprotonated form and nicotine in a diprotonated form. In one embodiment, the gel or crystalline powder contains nicotine in an unprotonated form, nicotine in a monoprotonated form and nicotine in a diprotonated form.

[0036] In one embodiment, at least 5 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 10 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 15 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 20 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 25 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 30 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 35 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 40 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 45 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 50 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 55 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 60 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 65 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 70 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 75 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 80 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 85 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In another embodiment, at least 90 wt% of the nicotine present in the gel or crystalline powder is in the protonated form.In one embodiment, at least 95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 99 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, at least 99.9 wt% of the nicotine present in the gel or crystalline powder is in the protonated form.

[0037] In one embodiment, 50-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 55-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 60-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 65-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 70-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 75-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 80-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In one embodiment, 85-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form. In another embodiment, 90-95 wt% of the nicotine present in the gel or crystalline powder is in the protonated form.

[0038] The relative amounts of nicotine present in the formulation in protonated form are specified herein. These amounts can be readily calculated by those skilled in the art. Nicotine (3-(1-methylpyrrolidine-2-yl)pyridine) is a diacid base with a pKa of 3.12 for the pyridine ring and 8.02 for the pyrrolidine ring. Nicotine can exist in pH-dependent protonated (mono- and di-) and unprotonated (free base) forms, which have different bioavailability. [ka]

[0039] The distribution of protonated and unprotonated nicotine will change with varying pH levels. [ka]

[0040] The proportion of unprotonated nicotine becomes dominant at high pH levels, while decreasing pH leads to an increase in the proportion of protonated nicotine (mono- or di-, depending on pH). If the relative proportion of protonated nicotine and the total amount of nicotine in a sample are known, the absolute amount of protonated nicotine can be calculated.

[0041] The relative proportion of protonated nicotine in a compound can be calculated using the Henderson-Hasselbalch equation, which expresses pH as the derivation of the acid dissociation constant. The Henderson-Hasselbalch equation is widely used in chemistry and biology. Consider the following equilibrium: [ka]

[0042] The Henderson-Hasselbalch equation for this equilibrium is:

number

[0043] In the formula, [B] is the amount of unprotonated nicotine (i.e., free base), [BH+] is the amount of protonated nicotine (i.e., conjugate acid), and pKa is the reference pKa value of the pyrrolidine ring nitrogen of nicotine (pKa = 8.02). The relative proportion of protonated nicotine can be derived from the alpha value of unprotonated nicotine calculated from the Henderson-Hasselbalch equation as follows:

number

[0044] The pKa values ​​of nicotine-containing compounds were determined using the basic method described in "Spectroscopic investigations into the acid-base properties of nicotine at different temperatures" by Peter M. Clayton, Carl A. Vas, Tam TTBui, Alex F. Drake, and Kevin McAdam, Anal. Methods, 2013, 5, 81-88.

[0045] acid As discussed herein, each of the gels and crystalline powders contains a water-soluble acid. The term "water-soluble" means that the acid has a solubility in water of at least 20 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 50 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 100 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 200 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 300 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 400 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 500 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 600 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 700 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 800 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 900 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 1000 g / L at 20°C. In one embodiment, the acid has a solubility in water of at least 1100 g / L at 20°C.

[0046] In one aspect, the acid is an organic acid. In one aspect, the acid is a carboxylic acid. In one aspect, the acid is an organic carboxylic acid.

[0047] In one embodiment, the acid is selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof. In one embodiment, the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, lactic acid, sorbic acid, and mixtures thereof. In one embodiment, the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, and mixtures thereof. In one embodiment, the acid is at least citric acid. In one embodiment, the acid consists of citric acid.

[0048] In one embodiment, the acid is a mixture of (i) citric acid and (ii) a further acid other than citric acid. In one embodiment, the acid is a mixture of (i) citric acid and (ii) a further acid selected from the group consisting of acetic acid, lactic acid, formic acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, sorbic acid, propionic acid, phenylacetic acid and mixtures thereof. In one embodiment, the acid is a mixture of (i) citric acid and (ii) a further acid selected from the group consisting of benzoic acid, levulinic acid, lactic acid, sorbic acid and mixtures thereof. In one embodiment, the acid is a mixture of (i) citric acid and (ii) a further acid selected from the group consisting of benzoic acid, levulinic acid and mixtures thereof.

[0049] In one embodiment, the acid is selected from acids having a pka of 2 to 5. In one embodiment, the acid is a weak acid. In one embodiment, the acid is a weak organic acid.

[0050] The molar ratio of acid to nicotine may be selected as desired. In one embodiment, the molar ratio of acid to nicotine is 5:1 to 1:5. In one embodiment, the molar ratio of acid to nicotine is 4:1 to 1:4. In one embodiment, the molar ratio of acid to nicotine is 3:1 to 1:3. In one embodiment, the molar ratio of acid to nicotine is 2:1 to 1:2. In one embodiment, the molar ratio of acid to nicotine is 1.5:1 to 1:1.5. In one embodiment, the molar ratio of acid to nicotine is 1.2:1 to 1:1.2. In one embodiment, the molar ratio of acid to nicotine is 5:1 to 1:1. In one embodiment, the molar ratio of acid to nicotine is 4:1 to 1:1. In one embodiment, the molar ratio of acid to nicotine is 3:1 to 1:1. In one embodiment, the molar ratio of acid to nicotine is 2:1 to 1:1. In one embodiment, the molar ratio of acid to nicotine is 1.5:1 to 1:1. In another embodiment, the molar ratio of acid to nicotine is 1.2:1 to 1:1.

[0051] In one embodiment, the total acid content present in the gel or crystalline powder is 5 molar equivalents or less based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 4 molar equivalents or less based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 3 molar equivalents or less based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 2 molar equivalents or less based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 1 molar equivalent or less based on nicotine.

[0052] In one embodiment, the total acid content present in the gel or crystalline powder is 0.1 molar equivalents or more based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 0.2 molar equivalents or more based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 0.3 molar equivalents or more based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 0.4 molar equivalents or more based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 0.5 molar equivalents or more based on nicotine. In one embodiment, the total acid content present in the gel or crystalline powder is 0.7 molar equivalents or more based on nicotine.

[0053] In one embodiment, the acid is present in an amount of 6 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 4 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 4 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 4 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 4 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 4 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 3 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 3 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 3 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 3 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 3 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 2 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 2 wt% based on the total weight of the gel or crystalline powder.In one embodiment, the acid is present in an amount of 0.02 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 1 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.6 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 0.6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 0.6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 0.6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 0.6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 0.6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 0.5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 0.5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 0.5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 0.5 wt% based on the total weight of the gel or crystalline powder.In one embodiment, the acid is present in an amount of 0.2 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 0.2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 0.2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 0.2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.08 to 0.2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.01 to 0.1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.02 to 0.1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.05 to 0.1 wt% based on the total weight of the gel or crystalline powder. In another embodiment, the acid is present in an amount of 0.08 to 0.1 wt% based on the total weight of the gel or crystalline powder.

[0054] In one embodiment, the acid is present in an amount of 60 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 60 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 60 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 60 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 60 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 50 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 50 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 50 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 50 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 40 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 40 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 40 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 40 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 40 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 30 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 30 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 30 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 30 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 30 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 20 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 20 wt% based on the total weight of the gel or crystalline powder.In one embodiment, the acid is present in an amount of 0.2 to 20 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 20 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 20 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 10 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 10 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 10 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 10 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 10 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 1 to 10 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 6 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 1 to 6 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 5 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 5 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 2 wt% or less based on the total weight of the gel or crystalline powder.In one embodiment, the acid is present in an amount of 0.1 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 2 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 1 wt% or less based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.1 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.2 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.5 to 1 wt% based on the total weight of the gel or crystalline powder. In one embodiment, the acid is present in an amount of 0.8 to 1 wt% based on the total weight of the gel or crystalline powder.

[0055] The amount of acid and the solubility of the acid may be selected so that a given amount of acid dissolves in water. In one embodiment, at least 20% of the acid dissolves in water at 20°C. In one embodiment, at least 20% of the acid dissolves in water at 25°C. In one embodiment, at least 20% of the acid dissolves in water at 30°C. In one embodiment, at least 35% of the acid dissolves in water at 20°C. In one embodiment, at least 40% of the acid dissolves in water at 20°C. In one embodiment, at least 45% of the acid dissolves in water at 20°C. In one embodiment, at least 50% of the acid dissolves in water at 20°C. In one embodiment, at least 55% of the acid dissolves in water at 20°C.

[0056] In one embodiment, the acid is selected from acids that are solid at 25°C.

[0057] fragrance As discussed herein, the crystalline powder comprises one or more fragrances or flavoring components. In one embodiment, the gel further comprises one or more fragrances or flavoring components. As used herein, the terms “fragrance” and “flavoring” refer to materials that can be used in adult consumer products to produce a desired taste or aroma, where local control is permitted. The fragrances and flavorings include extracts (e.g., licorice, hydrangea, magnolia leaf, chamomile, fenugreek, clove, menthol, Japanese mint, aniseed, cinnamon, herbs, wintergreen, cherry, berry, peach, apple, Drambuie, bourbon, scotch, whiskey, spearmint, peppermint, lavender, cardamom, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, cassia, caraway, cognac, jasmine, ylang-ylang). It may also contain other additives such as peppermint oil (derived from sage, fennel, bell pepper, ginger, anise, coriander, coffee, or any species of the genus Mentha), flavor enhancers, bitter taste receptor site blockers, sensory receptor site activators or stimulants, sugars and / or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and charcoal, chlorophyll, minerals, plant substances, or breath fresheners. These may be imitation ingredients, synthetic ingredients, natural ingredients, or blends thereof. They may be in any suitable form, e.g., oil, liquid, or powder. One or more fragrances may be selected from the group consisting of (4-(para-)methoxyphenyl)-2-butanone, vanillin, γ-undecalactone, menthone, 5-propenylguaetol, menthol, para-menta-8-thiol-3-one, and mixtures thereof. In one embodiment, the fragrance is at least menthol.

[0058] If present, one or more fragrances may be present in any suitable amount. In one embodiment, one or more fragrances are present in a total amount of 10 wt.% or less based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 7 wt.% or less based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 5 wt.% or less based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 4 wt.% or less based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 3 wt.% or less based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 2 wt.% or less based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 1 wt.% or less based on the gel or crystalline powder.

[0059] In one embodiment, one or more fragrances are present in a total amount of 0.01 to 5 wt.% based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 0.01 to 4 wt.% based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 0.01 to 3 wt.% based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 0.01 to 2 wt.% based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 0.01 to 1 wt.% based on the gel or crystalline powder. In one embodiment, one or more fragrances are present in a total amount of 0.01 to 0.5 wt.% based on the gel or crystalline powder.

[0060] Encapsulation materials As discussed herein, the crystalline powder includes an encapsulating material. The encapsulating material may be present in the crystalline powder in any suitable amount.

[0061] In one embodiment, the encapsulating material is present in a total amount of 12 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 10 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 9 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 8 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 7 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 6 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 5 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 4 wt.% or less based on the crystalline powder. In one embodiment, the encapsulating material is present in a total amount of 3 wt.% or less based on the crystalline powder.

[0062] In one embodiment, one or more encapsulation materials are selected from the group consisting of micelles, cyclodextrins, calixarenes, metal-organic skeletons, dendrimers, polymers, hydrophilic colloids, pollen spores, yeast particles, porous silica, and mixtures thereof. In one embodiment, one or more encapsulation materials are selected from cyclodextrins and mixtures thereof.

[0063] One or more cyclodextrins may be selected from the group consisting of unsubstituted cyclodextrins, substituted cyclodextrins, and mixtures thereof. In one embodiment, at least one cyclodextrin is an unsubstituted cyclodextrin. In one embodiment, one or more cyclodextrins are selected from the group consisting of unsubstituted cyclodextrins. In one embodiment, at least one cyclodextrin is a substituted cyclodextrin. In one embodiment, one or more cyclodextrins are selected from the group consisting of substituted cyclodextrins.

[0064] In one embodiment, one or more cyclodextrins are selected from the group consisting of unsubstituted (α)-cyclodextrins, substituted (α)-cyclodextrins, unsubstituted (β)-cyclodextrins, substituted (β)-cyclodextrins, unsubstituted (γ)-cyclodextrins, substituted (γ)-cyclodextrins, and mixtures thereof. In one embodiment, one or more cyclodextrins are selected from the group consisting of unsubstituted (β)-cyclodextrins, substituted (β)-cyclodextrins, and mixtures thereof.

[0065] In one embodiment, one or more cyclodextrins are selected from the group consisting of unsubstituted (α)-cyclodextrins, unsubstituted (β)-cyclodextrins, unsubstituted (γ)-cyclodextrins, and mixtures thereof. In one embodiment, one or more cyclodextrins are selected from unsubstituted (β)-cyclodextrins.

[0066] In one embodiment, one or more cyclodextrins are selected from the group consisting of substituted (α)-cyclodextrins, substituted (β)-cyclodextrins, substituted (γ)-cyclodextrins, and mixtures thereof. In one embodiment, one or more cyclodextrins are selected from substituted (β)-cyclodextrins. Chemical substitutions at the 2-, 3-, and 6-hydroxyl sites, particularly substitutions at the 2-position, are envisioned.

[0067] In one embodiment, one or more cyclodextrins are selected from the group consisting of 2-hydroxypropyl-α-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin, and mixtures thereof. In one embodiment, one or more cyclodextrins are at least 2-hydroxypropyl-α-cyclodextrin. In one embodiment, one or more cyclodextrins are at least 2-hydroxypropyl-β-cyclodextrin. In one embodiment, one or more cyclodextrins are at least 2-hydroxypropyl-γ-cyclodextrin.

[0068] 2-hydroxypropyl derivatives of cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin, increased solubility in water compared to basic cyclodextrins such as β-cyclodextrin.

[0069] One or more cyclodextrins may or may not be present in the crystalline powder in any suitable amount. In one embodiment, one or more cyclodextrins are present in a total amount of 12 wt.% or less based on the crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 10 wt.% or less based on the crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 9 wt.% or less based on the crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 8 wt.% or less based on the crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 7 wt.% or less based on the crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 6 wt.% or less based on the crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 5 wt.% or less based on crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 4 wt.% or less based on crystalline powder. In one embodiment, one or more cyclodextrins are present in a total amount of 3 wt.% or less based on crystalline powder.

[0070] method As discussed herein, in one embodiment, (i) Based on the gel, add 1-20 wt.% of water, (ii) Nicotine and, (iii) Water-soluble acids and A method for producing a gel containing, (a) (i) 50-90 wt.% of water based on the nicotine solution, (ii) Nicotine, and (iii) Water-soluble acid The steps include preparing a nicotine solution containing, (b) The step of dehydrating the nicotine solution to obtain a gel A method is provided that includes this.

[0071] As discussed herein, in one embodiment, (i) Based on the crystalline powder, add less than 15 wt% of water, (ii) Nicotine and, (iii) A water-soluble acid, (iv) One or more fragrances, (v) Encapsulation material and A method for producing a crystalline powder containing, (a) (i) 50-95 wt.% of water based on the nicotine solution, (ii) Nicotine, (iii) a water-soluble acid; (iv) One or more fragrances, and (v) Encapsulation material The steps include preparing a nicotine solution containing, (b) The step of dehydrating the nicotine solution to obtain a crystalline powder. A method is provided that includes this.

[0072] In one embodiment, in a method for producing a gel, a nicotine solution is prepared containing 55-90 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing a gel, a nicotine solution is prepared containing 60-90 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing a gel, a nicotine solution is prepared containing 65-90 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing a gel, a nicotine solution is prepared containing 70-90 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing a gel, a nicotine solution is prepared containing 75-90 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing a gel, a nicotine solution is prepared containing 75-85 wt.% of water based on a nicotine solution.

[0073] In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 55-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 60-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 65-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 70-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 75-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 80-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing crystalline powder, a nicotine solution is prepared containing 85-95 wt.% of water based on a nicotine solution. In one embodiment, in a method for producing a crystalline powder, a nicotine solution is prepared based on a nicotine solution, containing 90-95 wt.% of water.

[0074] A typical method is described as follows:

[0075] During preparation, the formulation is prepared, stirred, and heated to approximately 40°C. This allows for proper mixing of the components throughout the process. At this temperature, cyclodextrins (such as (2-hydroxypropyl)-β-cyclodextrin) are thermally stable and should be added first. Typically, the maximum addition amount should not exceed 10% w / w.

[0076] The amount added will depend on the percentage of the fragrance composition, and it is expected that a smaller amount will be needed to achieve a water content of 90%.

[0077] Next, nicotine may be added, taking note that since nicotine is already miscible with water, no precipitate will be observed. A typical addition amount range is 0.1–1.2 wt%.

[0078] Flavoring components should be added last, due to their generally higher binding energy with the cyclodextrin host (relative to nicotine). The inventors found that the greater the difference in binding energy, the less likely a competitive complex formation mechanism with nicotine is. In the case of menthol, the approximate binding energy is -4.13 kcal.mol. -1 (Nicotine) and -5.06 kcal.mol -1 (Menthol). In this example, depending on the amount added, a slight precipitate of menthol may be observed when cooling from 40°C to ambient temperature. Then, microfiltration may be performed to remove any excess menthol that did not form a complex with the cyclodextrin.

[0079] An aqueous solution of citric acid and nicotine was prepared using a molar equivalent ratio of 1:1. The resulting liquid was bright orange in color and showed no signs of separation. Using a desiccator, water and any water-soluble impurities were removed from the liquid, thereby producing a bright orange precipitate with gel-like viscosity. This is sometimes called "nicotinium citrate" gel. The formulation can then be prepared as described above, except that no heating or filtration steps are required. When nicotinium citrate gel is added in place of nicotine at the final formulation stage, the nicotinium citrate gel dissociates into the corresponding nicotinium(+) and citrate(-) ions. Since nicotinium(+) is originally larger than nicotine (nicotinium(+) takes a proton from the corresponding citrate(-) ion), and menthol is now the preferred guest species, nicotinium(+) does not interfere with the menthol-cyclodextrin complex formation mechanism. Therefore, no visible menthol precipitate is present. Subjectively, the formulation is stronger when prepared in this way. Flavor delivery is optimized and no longer gradually weakens with increasing nicotine concentration. Nicotine delivery is also optimized because nicotine is now present in the particulate phase rather than the vapor phase, and therefore can penetrate deep into the lungs. The presence of citrate- (-) ions complements the nicotine properties by providing an inherent bitterness and improved throat catch. This effect makes it possible to further reduce the nicotine concentration.

[0080] Therefore, in one way, (i) Based on the crystalline powder, add less than 15 wt% of water, (ii) Nicotine and, (iii) A water-soluble acid, (iv) One or more fragrances, (v) Encapsulation material and A method for producing a crystalline powder containing, (a) (i) Based on the gel, a quantity of water of 1-20 wt.% (ii) Nicotine, and (iii) Water-soluble acid The steps include preparing a gel containing and (b) (iii) a water-soluble acid; (iv) One or more fragrances, and (v) Encapsulation material The steps include preparing a fragrance solution containing and The steps include: bringing the gel into contact with a fragrance solution to produce a nicotine solution, (c) The step of dehydrating the nicotine solution to obtain a crystalline powder. A method is provided that includes this.

[0081] As discussed herein, in one embodiment, (i) Based on the gel, a quantity of water of 1-20 wt.% (ii) Nicotine, and (iii) Water-soluble acid A method is provided for rehydrating a gel containing a substance, the method comprising the step of bringing the gel into contact with water.

[0082] As discussed herein, in one embodiment, (i) A quantity of water less than 15 wt.% based on the crystalline powder, (ii) Nicotine, (iii) a water-soluble acid; (iv) One or more fragrances, and (v) Encapsulation material A method is provided for rehydrating a crystalline powder containing a substance, the method comprising the step of bringing the crystalline powder into contact with water.

[0083] The gel or crystalline powder may be contained or delivered by any means. In one embodiment, the present invention provides a contained gel or crystalline powder comprising (a) one or more containers and (b) the gel or crystalline powder as defined herein. The container may be any suitable container for, for example, enabling the storage or delivery of the gel or crystalline powder. In one embodiment, the container is configured to engage with an electron aerosol supply system. The container may be configured to fluidly communicate with an electron aerosol supply system so that the gel or crystalline powder can be delivered to the electron aerosol supply system. As stated above, this disclosure relates to a container that can be used in an electron aerosol supply system such as an e-cigarette. Throughout the following description, the term “e-cigarette” will be used, but this term can be used interchangeably with electron aerosol supply system.

[0084] As discussed herein, the containers of the present invention are typically provided for the delivery of a gel or crystalline powder to or within an e-cigarette. The gel or crystalline powder may be retained within the e-cigarette or may be sold as a separate container for subsequent use with or within the e-cigarette. As will be understood by those skilled in the art, the e-cigarette may include a unit known as a removable cartomizer, which typically comprises a reservoir for the gel or crystalline powder, a wicking material, and a heating element for vaporizing the gel or crystalline powder. In some e-cigarettes, the cartomizer is part of a molded device and is not removable. In one embodiment, the container is either a cartomizer or part of a cartomizer. In one embodiment, the container is either not a cartomizer or part of a cartomizer, but a container such as a tank, which can be used to deliver nicotine gel or crystalline powder to or within an e-cigarette.

[0085] In one embodiment, the container is part of the e-cigarette. Thus, in a further embodiment, the present invention provides an electronic aerosol supply system comprising an aerosolizer for aerosolizing the gel or crystalline powder, as defined herein, for inhalation by a user of the electronic aerosol supply system, and a power supply comprising a battery or power source for supplying power to the aerosolizer.

[0086] In addition to the gel or crystalline powder of the present invention and systems such as containers and electronic aerosol supply systems for containing them, the present invention also provides a method for improving the sensory properties of aerosolized nicotine. In a further embodiment, the present invention provides a method for improving the storage stability of aerosolized nicotine gel or crystalline powder.

[0087] References to improvements in the sensory characteristics of vaporized nicotine may include improvements in the smoothness of vaporized nicotine as perceived by the user.

[0088] The method of the present invention may include additional steps before, after, or between one or more of the listed steps.

[0089] Herein, the present invention will be described in more detail, merely as an example, with reference to the attached drawings. [Brief explanation of the drawing]

[0090] [Figure 1] This graph shows the change in psKa2 in relation to nicotine concentration. [Examples]

[0091] The present invention will now be described with reference to the following non-limiting examples.

[0092] Example 1 Experiments revealed that the solubility of the crystalline powder in isopropyl alcohol (IPA) was approximately 1 g / 100 mL at 20°C after vigorous stirring. Three 20 ml crystalline powder extracts were prepared and analyzed for nicotine / menthol and water content using GC-FID.

[0093] N-heptadecane was added to each extract for nicotine / menthol measurement at a concentration of 125 mg / mL as an internal standard, and ethanol (100%) was added to each extract for water measurement at a concentration of 125 mg / mL as an internal standard.

[0094] In all three samples, menthol was measured below the reporting limit of 0.0747 mg / ml. Two of the samples contained nicotine, which was measured below the reporting limit of 0.0251 mg / ml for this method.

[0095] Water was found in all samples within the limits of the calibration curve for this method (0.00–0.09 mg / ml).

[0096] Example 2 Method for producing nicotinium citrate Using a molar equivalent ratio of 1:1, 5 ml of aqueous solution of 0.2044 g of citric acid and 0.2035 g of nicotine was prepared. The resulting liquid was homogeneous and showed no signs of separation. No heating or filtration steps were necessary.

[0097] Dehydration method Using a desiccator and silica gel, water and all water-soluble impurities were removed from the liquid under vacuum for 24 hours, resulting in a precipitate with gel-like viscosity. The resulting gel was air-dried overnight. This was called "nicotinium citrate" gel.

[0098] Combination of fragrance with nicotinium citrate First, a 10 ml aqueous solution was prepared by stirring 0.9% (w / w) menthol and 9% (w / w) 2-hydroxypropyl-β-cyclodextrin on a 40°C hot plate for approximately 30 minutes. Next, the aqueous solution containing the fragrance compound and encapsulation material was added to the dry gel and stirred for a further 30 minutes to dissolve. This resulted in a homogeneous solution with no signs of separation.

[0099] Method for producing crystalline powder Next, the resulting solution was dried by applying the same dehydration method over a week. This yielded a crystalline powder (solid) containing nicotine, flavoring, encapsulating material, and approximately 7% (w / w) water. Subsequently, the powder was rehydrated by simply adding water and stirring. After stirring for 3 minutes, the powder was completely rehydrated, giving a clear solution.

[0100] To conduct a sensory evaluation, 1.5 g of crystalline powder was dissolved in 10 ml of water by stirring at room temperature for 3 minutes. The resulting solution was then filled into a commercially available nebulizer. The sensory perception of the rehydrated formulation was evaluated by the panelists as acceptable.

[0101] Without departing from the scope and spirit of the present invention, various modifications and variations of the present invention will be apparent to those skilled in the art. Although the present invention has been described in relation to certain preferred embodiments, it should be understood that the present invention as described in the claims should not be unduly limited to such specific embodiments. In fact, various modifications of the described modes for carrying out the present invention, which are obvious to those skilled in the art in the chemical or related fields, are intended to fall within the scope of the following claims.

Claims

1. (i) Based on the gel, add 1 to 20 wt.% of water, (ii) Based on the gel, 20-75 wt.% of nicotine, (iii) A water-soluble acid having a solubility of at least 20 g / L in water at 20°C and A gel containing [a specific substance], with an acid-to-nicotine molar ratio of 5:1 to 1:

5.

2. The gel according to claim 1, wherein water is present in an amount of 1 to 15 wt.% based on the gel.

3. The gel according to claim 1 or 2, wherein water is present in an amount of 1 to 10 wt.% based on the gel.

4. The gel according to any one of claims 1 to 3, wherein the water-soluble acid is selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof.

5. The gel according to any one of claims 1 to 4, wherein the water-soluble acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, lactic acid, sorbic acid, and mixtures thereof.

6. The gel according to any one of claims 1 to 5, wherein the water-soluble acid is at least citric acid.

7. (i) Based on the gel, add 1 to 20 wt.% of water, (ii) Based on the gel, 20-75 wt.% of nicotine, (iii) A water-soluble acid having a solubility of at least 20 g / L in water at 20°C and A method for producing a gel containing the following, wherein the molar ratio of acid to nicotine is 5:1 to 1:5: (a) (i) 50-90 wt.% of water based on the nicotine solution, (ii) Nicotine, and (iii) The water-soluble acid The steps include preparing a nicotine solution containing, (b) The step of dehydrating the nicotine solution to obtain the gel Methods that include...

8. The method according to claim 7, wherein the gel is the gel described in any one of claims 2 to 6.

9. (i) Based on the gel, 1 to 20 wt.% of water (ii) Nicotine in amounts of 20-75 wt.% based on the gel, and (iii) A water-soluble acid having a solubility of at least 20 g / L in water at 20°C A method for rehydrating a gel containing an acid-to-nicotine molar ratio of 5:1 to 1:5, comprising the step of bringing the gel into contact with water.

10. (a) A container and (b) (i) Based on the gel, 1 to 20 wt.% of water (ii) Nicotine in amounts of 20-75 wt.% based on the gel, and (iii) A water-soluble acid having a solubility of at least 20 g / L in water at 20°C A gel containing an acid-to-nicotine molar ratio of 5:1 to 1:5 The contained gel, including

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