RU2787865C2 - Gel and crystalline powder - Google Patents

Abstract

FIELD: smoking devices.

SUBSTANCE: invention relates to a gel and a crystalline powder used to produce a solution used in an aerosol providing apparatus. Gel contains water in an amount from 1 to 20 wt.% relative to the mass of the gel, nicotine and a water-soluble acid, wherein the molar ratio of acid to nicotine is from 3:1 to 1:3. Also proposed is a crystalline powder containing water in an amount less than 15 wt.% relative to the mass of the crystalline powder, nicotine, a water-soluble acid, one or multiple flavouring substances, and an encapsulating material.

EFFECT: production of a gel, dissolving easily without heating, allows avoiding loss of volatile nicotine and/or flavouring substance in electronic cigarettes, and easily dehydrated resulting in a crystalline powder for producing an aerosolising liquid in electronic cigarettes.

35 cl, 2 ex, 1 dwg

Description

The technical field to which the invention belongs

The present disclosure relates to a gel and crystalline powder, a method for their preparation, a container containing said gel and powder, a device containing them, as well as methods and uses of such a gel and crystalline powder.

State of the art

Electronic aerosol delivery systems, such as electronic cigarettes, typically contain a reservoir of liquid to be vaporized, typically containing nicotine. When a user inhales through such a device, the heater is activated so as to vaporize a small amount of liquid which is subsequently inhaled by the user.

The use of e-cigarettes in the UK is growing rapidly and it is estimated that over a million people are currently using them in the UK.

One of the problems encountered in designing such systems is to provide an inhalable aerosol from the aerosol supply device that provides an acceptable user experience. Some consumers may prefer e-cigarettes that produce an aerosol that very closely "simulates" the smoke inhaled from a tobacco product such as a cigarette. Aerosols from electronic cigarettes and smoke from tobacco products such as cigarettes provide the user with a complex chain of flavor sensations in the mouth, nicotine absorption in the mouth and throat, followed by nicotine absorption in the lungs. These various aspects are described by users in terms of flavor, intensity/quality, impact, irritation/softness, and nicotine satisfaction. Nicotine contributes to some of these factors and is strongly associated with factors such as exposure, irritation and mildness; these parameters are easily perceived by consumers, and electronic cigarettes can provide consumers with excessive or excessively weak specified sensations, depending on individual preferences. Satisfaction with nicotine is particularly complex because it is a result of both the amount and rate at which nicotine is absorbed from the oral mucosa, typically vapor phase nicotine, and the amount and rate at which nicotine is absorbed from the lungs, typically particulate nicotine. phase of the inhaled aerosol. Each of these factors and their balance can greatly contribute to consumer acceptance of an e-cigarette. Therefore, it is desirable for manufacturers of electronic cigarettes to offer means to optimize the overall perception of smoking an electronic cigarette.

Disclosure of invention

In one aspect, a gel is provided comprising:

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) a water soluble acid.

In one aspect, a crystalline powder is provided that contains

(i) water in an amount of less than 15% by weight. in relation to the mass of crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material.

In one aspect, a method is provided for preparing a gel containing

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) a water soluble acid;

moreover, this method includes the steps:

(a) providing a nicotine solution containing

(i) water in an amount of 50 to 90% by weight, based on the weight of the nicotine solution;

(ii) nicotine; as well as

(iii) a water soluble acid;

(b) dehydrogenating said nicotine solution to obtain a gel.

In one aspect, a method is provided for preparing a crystalline powder containing

(i) water in an amount of less than 15% by weight based on the weight of the crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

moreover, this method includes the steps:

(a) providing a nicotine solution containing

(i) water in an amount of from 50 to 95 wt.% in relation to the mass of the nicotine solution;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

(b) dehydrogenating said nicotine solution to obtain a crystalline powder.

In one aspect, a method is provided for rehydrating a gel containing

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) a water soluble acid;

wherein said method includes the step of contacting said gel with water.

In one aspect, a method is provided for rehydrating a crystalline powder containing

(i) water in an amount of less than 15% by weight based on the weight of the crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

wherein said method includes the step of contacting said crystalline powder with water.

In one aspect, a containerized gel is provided comprising:

(a) a container; as well as

(b) a gel containing:

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) a water soluble acid.

In one aspect, a containerized crystalline powder is provided comprising:

(a) a container; as well as

(b) a crystalline powder containing:

(i) water in an amount of less than 15% by weight based on the weight of the crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material.

Implementation of the invention

As discussed herein, in one aspect, a gel is provided that contains (i) water in an amount of 1 to 20% by weight based on the weight of the gel; (ii) nicotine; and (iii) a water soluble acid. In a further aspect, a crystalline powder is provided comprising (i) less than 15% by weight water. in relation to the mass of crystalline powder; (ii) nicotine; (iii) a water soluble acid; (iv) one or more flavoring substances; and (v) an encapsulating material.

The inventors have found that an advantageous system can be provided wherein the gel is derived from nicotine; and this gel and water-soluble acid can be used to obtain a crystalline powder containing water, nicotine; water soluble acid; one or more flavoring substances; and encapsulating material. The gel is obtained from a solution of nicotine, water and a water-soluble acid, which is subsequently dehydrated to form a gel. The gel is easily transported without the need to transport unnecessary amounts of water. Gels are also easy to handle and avoid the leakage problems associated with liquids. If necessary, the gel can then be used to make a solution of water and nicotine; water soluble acid; one or more flavoring substances; and encapsulating material. This is achieved by contacting the specified gel with water, one or more flavoring substances; and encapsulating material. This method is another advantage because the gel can be easily dissolved without heating. This avoids loss of volatile nicotine and/or flavor. This additional solution can be dehydrogenated to give a crystalline powder. This crystalline powder contains the components necessary to obtain an aerosolizable liquid. The preparation of this liquid may be performed by the manufacturer or the end user. The crystalline powder is particularly preferred because the inventors have found that it will only dissolve when sufficient water is present, and thus any solution delivered will not be too concentrated for nicotine. This is important to ensure that the end user is not provided with an undesirable concentration of nicotine solution.

For ease of reference, these and other aspects of the present invention are now discussed under their respective section headings. However, the ideas in each section are not necessarily limited to each particular section.

As one of skill in the art will appreciate, nicotine can exist in a non-protonated form, a monoprotonated form, or a diprotonated form. The structure of each of these forms is presented below.

Reference in the specification to the protonated form means both monoprotonated nicotine and diprotonated nicotine. Reference in the specification to amounts in protonated form means the combined amount of monoprotonated nicotine and diprotonated nicotine. Furthermore, when reference is made to a fully protonated composition, it should be understood that very small amounts of unprotonated nicotine may be present at any given time, eg less than 1% of unprotonated nicotine.

Water

As stated in the present description, the gel contains water in an amount of from 1 to 20 wt.% in relation to the weight of the gel. In one aspect, water is present in an amount of 1 to 20% by weight, based on the weight of the gel. In one aspect, water is present in an amount of 1 to 15% by weight, based on the weight of the gel. In one aspect, water is present in an amount of 1 to 10% by weight based on the weight of the gel.

As mentioned in the present description, the crystalline powder contains water in an amount of less than 15 wt.% in relation to the mass of the crystalline powder. In one aspect, water is present in an amount of less than 10% by weight based on the weight of the crystalline powder. In one aspect, water is present in an amount of less than 8% by weight based on the weight of the crystalline powder.

Nicotine

Nicotine compositions can be provided that have the desired flavor, impact, irritation, mildness, and/or nicotine satisfaction properties for the user.

In one aspect, nicotine is present in an amount of not more than 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 10% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 10% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of no more than 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 8% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 8% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of not more than 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 6% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 6% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of not more than 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 5% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 5% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of no more than 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 4% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 4% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of no more than 3% by weight, based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 3% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 3% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of no more than 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.01 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.02 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.05 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.08 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.1 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.2 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 0.5 to 2% by weight based on the total weight of the crystalline powder. In one aspect, nicotine is present in an amount of 1 to 2% by weight based on the total weight of the crystalline powder.

In one aspect, nicotine is present in an amount of no more than 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 50 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 60 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 70 to 90% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 80 to 90% by weight based on the total weight of the gel.

In one aspect, nicotine is present in an amount of no more than 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 85% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 50 to 85% by weight based on the total weight of the gel.

In one aspect, nicotine is present in an amount of no more than 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 50 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 60 to 80% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 70 to 80% by weight based on the total weight of the gel.

In one aspect, nicotine is present in an amount of no more than 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 75% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 50 to 75% by weight based on the total weight of the gel.

In one aspect, nicotine is present in an amount of no more than 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 50 to 70% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 60 to 70% by weight based on the total weight of the gel.

In one aspect, nicotine is present in an amount of no more than 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 60% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 50 to 60% by weight based on the total weight of the gel.

In one aspect, nicotine is present in an amount of no more than 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 1 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 5 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 10 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 15 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 20 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 25 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 30 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 35 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 40 to 50% by weight based on the total weight of the gel. In one aspect, nicotine is present in an amount of 45 to 50% by weight based on the total weight of the gel.

The gel or crystalline powder contains nicotine in its protonated form. The gel or crystalline powder may contain nicotine in a non-protonated form. In one aspect, the gel or crystalline powder contains nicotine in a non-protonated form and nicotine in a monoprotonated form. In one aspect, the gel or crystalline powder contains nicotine in a non-protonated form and nicotine in a diprotonated form. In one aspect, the gel or crystalline powder contains nicotine in unprotonated form, nicotine in monoprotonated form, and nicotine in diprotonated form.

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

In one aspect, 50 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, from 55 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, from 60 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, from 65 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, from 70 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, from 75% to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, 80 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, 85 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form. In one aspect, 90 to 95% by weight of the nicotine present in the gel or crystalline powder is in protonated form.

The corresponding amounts of nicotine present in the composition in protonated form are given herein. These quantities can be easily calculated by those skilled in the art. Nicotine, which is 3-(1-methylpyrrolidin-2-yl)pyridine, is a dibasic base characterized by pKa values of 3.12 for the pyridine ring and 8.02 for the pyrrolidine ring. It can exist in pH-dependent protonated (mono- and di-) and non-protonated (free base) forms, which are characterized by different bioavailability.

The distribution of protonated and non-protonated nicotine will vary with different pH elevations.

The proportion of non-protonated nicotine will predominate at high pH values, while a decrease in pH will lead to an increase in the proportion of protonated nicotine (mono- or di- depending on the pH value). If the relative proportion of protonated nicotine and the total amount of nicotine in the sample are known, the absolute amount of protonated nicotine can be calculated.

The relative proportion of protonated nicotine in a composition can be calculated using the Henderson-Hasselbach equation, which describes the pH value as a derivative of the acid dissociation constant equation, and which is widely used in chemical and biological systems. The following equilibrium is considered:

The Henderson-Hasselbach equation for this equilibrium is:

where [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 pKa reference value for the nitrogen atom of the pyrrolidine ring of nicotine (pKa = 8 .02). The relative proportion of protonated nicotine can be derived from the alpha value for non-protonated nicotine calculated from the Henderson-Hasselbach equation as:

Determination of pKa values for nicotine solutions can be done using the basic approach described in "Spectroscopic investigations into the acid-base properties of nicotine at different temperatures", Peter M. Clayton, Carl A. Vas, Tam T. T. Bui, Alex F. Drake and Kevin McAdam, Anal. Methods, 2013, 5, 81-88.

Acid

As discussed here, each of the gel and crystalline powder contains an acid that is water soluble. The term "water-soluble" means that the acid has a solubility in water of at least 20 g/l at 20°C. In one aspect, the acid has a water solubility of at least 50 g/l at 20°C. In one aspect, the acid has a water solubility of at least 100 g/l at 20°C. In one aspect, the acid has a water solubility of at least 200 g/l at 20°C. In one aspect, the acid has a water solubility of at least 300 g/l at 20°C. In one aspect, the acid has a water solubility of at least 400 g/l at 20°C. In one aspect, the acid has a water solubility of at least 500 g/l at 20°C. In one aspect, the acid has a water solubility of at least 600 g/l at 20°C. In one aspect, the acid has a water solubility of at least 700 g/l at 20°C. In one aspect, the acid has a water solubility of at least 800 g/l at 20°C. In one aspect, the acid has a water solubility of at least 900 g/l at 20°C. In one aspect, the acid has a water solubility of at least 1000 g/l at 20°C. In one aspect, the acid has a water solubility of at least 1100 g/l at 20°C.

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.

In one aspect, 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 aspect, the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, lactic acid, sorbic acid, and mixtures thereof. In one aspect, the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, and mixtures thereof. In one aspect, the acid is at least citric acid. In one aspect, the acid is citric acid.

In one aspect, the acid is a mixture of (i) citric acid and (ii) an additional acid that is not citric acid. In one aspect, the acid is a mixture of (i) citric acid and (ii) an additional 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 aspect, the acid is a mixture of (i) citric acid and (ii) an additional acid selected from the group consisting of benzoic acid, levulinic acid, lactic acid, sorbic acid, and mixtures thereof. In one aspect, the acid is a mixture of (i) citric acid and (ii) an additional acid selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof.

In one aspect, the acid is selected from acids having a pka of 2 to 5. In one aspect, the acid is a weak acid. In one aspect, the acid is a weak organic acid.

The molar ratio of acid to nicotine can be selected as desired. In one aspect, the molar ratio of acid to nicotine is from 5:1 to 1:5. In one aspect, the molar ratio of acid to nicotine is from 4:1 to 1:4. In one aspect, the molar ratio of acid to nicotine is from 3:1 to 1:3. In one aspect, the molar ratio of acid to nicotine is from 2:1 to 1:2. In one aspect, the molar ratio of acid to nicotine is from 1.5:1 to 1:1.5. In one aspect, the molar ratio of acid to nicotine is from 1.2:1 to 1:1.2. In one aspect, the molar ratio of acid to nicotine is from 5:1 to 1:1. In one aspect, the molar ratio of acid to nicotine is from 4:1 to 1:1. In one aspect, the molar ratio of acid to nicotine is from 3:1 to 1:1. In one aspect, the molar ratio of acid to nicotine is from 2:1 to 1:1. In one aspect, the molar ratio of acid to nicotine is from 1.5:1 to 1:1. In one aspect, the molar ratio of acid to nicotine is from 1.2:1 to 1:1.

In one aspect, the total acid content present in the gel or crystalline powder is not more than 5 molar equivalents based on nicotine. In one aspect, the total acid content present in the gel or crystalline powder is not more than 4 mole equivalents based on nicotine. In one aspect, the total acid content present in the gel or crystalline powder is not more than 3 molar equivalents based on nicotine. In one aspect, the total acid content present in the gel or crystalline powder is not more than 2 molar equivalents based on nicotine. In one aspect, the total acid content present in the gel or crystalline powder does not exceed 1 mol equivalent based on nicotine.

In one aspect, the total content of acid present in the gel or crystalline powder is not less than 0.1 mole equivalents based on nicotine. In one aspect, the total content of acid present in the gel or crystalline powder is not less than 0.2 mole equivalents based on nicotine. In one aspect, the total content of acid present in the gel or crystalline powder is not less than 0.3 mole equivalents based on nicotine. In one aspect, the total content of acid present in the gel or crystalline powder is not less than 0.4 mole equivalents based on nicotine. In one aspect, the total content of acid present in the gel or crystalline powder is not less than 0.5 mole equivalents based on nicotine. In one aspect, the total content of acid present in the gel or crystalline powder is not less than 0.7 mole equivalents based on nicotine.

In one aspect, the acid is present in an amount of no more than 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 4% by weight based on the weight of the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 4% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 4% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 4% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 4% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 3% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 3% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 3% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 3% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 3% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 0.6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 0.6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 0.6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 0.6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 0.6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 0.6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 0.5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 0.5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 0.5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 0.5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 0.5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 0.2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 0.2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 0.2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 0.2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 0.2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 0.1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.01 to 0.1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.02 to 0.1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.05 to 0.1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.08 to 0.1% by weight based on the total weight of the gel or crystalline powder.

In one aspect, the acid is present in an amount of no more than 60% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 60% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 60% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 60% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 60% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 50% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 50% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 50% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 50% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 40% by weight of the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 40% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 40% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 40% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 40% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 30% by weight of the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 30% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 30% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 30% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 30% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 20% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 20% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 20% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 20% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 20% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 10% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 10% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 10% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 10% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 10% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 1 to 10% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 1 to 6% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of no more than 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 2% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 5% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of not more than 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.1 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.2 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.5 to 1% by weight based on the total weight of the gel or crystalline powder. In one aspect, the acid is present in an amount of 0.8 to 1% by weight based on the total weight of the gel or crystalline powder.

The amount of acid and the solubility of the acid can be chosen such that a given amount of acid is soluble in water. In one aspect, at 20° C., at least 20% of the acid dissolves in water. In one aspect, at 25° C., at least 20% of the acid is dissolved in water. In one aspect, at 30° C., at least 20% of the acid is dissolved in water. In one aspect, at 20° C., at least 35% of the acid is dissolved in water. In one aspect, at 20° C., at least 40% of the acid is dissolved in water. In one aspect, at 20° C., at least 45% of the acid dissolves in water. In one aspect, at 20° C., at least 50% of the acid is dissolved in water. In one aspect, at 20° C., at least 55% of the acid dissolves in water.

In one aspect, the acid is selected from acids that are solid at 25°C.

Flavoring substance

As discussed herein, the crystalline powder contains one or more flavoring agents or flavoring components. In one aspect, the gel further comprises one or more flavoring agents or flavoring components. As used herein, the terms "flavour" and "flavor" refer to materials that, where local laws permit, may be added to a composition to create a desired flavor or aroma in an adult product. These may include extracts (eg, licorice, hydrangea, Japanese white magnolia leaves, chamomile, fenugreek, cloves, menthol, Japanese mint, aniseed, cinnamon, herbs, wintergreen, cherries, berries, peach, apple, Drambuie, bourbon, scotch , whiskey, spearmint, peppermint, lavender, cardamom, celery, cascarole, nutmeg, sandalwood, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, cassia, cumin, cognac, jasmine, ylang -ylang, sage, fennel, cloves, ginger, anise, coriander, coffee, or peppermint oil from any plant of the genus Mentha), flavor enhancers, bitterness receptor site blockers, sensory receptor site activators or stimulants, sugars and/or sugar substitutes (eg sucralose, acesulfame potassium, aspartame, saccharin, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or mannitol) and other additives such as charcoal, chlorophyll l, minerals, vegetable raw materials or breath fresheners. They may be artificial, synthetic or natural ingredients, or mixtures thereof. They may be in any suitable form, such as an oil, liquid or powder. One or more flavoring agents may be selected from the group consisting of 4-(p-methoxyphenyl)-2-butanone, vanillin, γ-undecalactone, menthone, 5-propenylguaethol, menthol, p-mentha-8-thiol-3-one and their mixtures. In one aspect, the flavoring agent is at least menthol.

One or more flavors may be present in any amount, if present. In one aspect, one or more flavors are present in a total amount of not more than 10% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of no more than 7% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of not more than 5% by weight, based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of not more than 4% by weight, based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of not more than 3% by weight, based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of not more than 2% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of not more than 1% by weight based on the weight of the gel or crystalline powder.

In one aspect, one or more flavors are present in a total amount of 0.01 to 5% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of 0.01 to 4% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in an amount of 0.01 to 3% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavors are present in a total amount of 0.01 to 2% by weight based on the weight of the gel or crystalline powder. In one aspect, one or more flavoring substances are present in an amount of from 0.01 to 1 wt.% in relation to the weight of the gel or crystalline powder. In one aspect, one or more flavoring substances are present in an amount of from 0.01 to 0.5 wt.% in relation to the weight of the gel or crystalline powder.

encapsulating material

As discussed herein, the crystalline powder contains an encapsulating material. The encapsulating material may be present in any suitable amount in the crystalline powder.

In one aspect, the encapsulating material is present in a total amount of not more than 12% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 10% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 9% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 8% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 7% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 6% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 5% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 4% by weight based on the weight of the crystalline powder. In one aspect, the encapsulating material is present in a total amount of not more than 3% by weight based on the weight of the crystalline powder.

In one aspect, one or more encapsulating materials are selected from the group consisting of micelles, cyclodextrins, calixarenes, organometallic scaffolds, dendrimers, polymers, hydrocolloids, pollen spores, yeast particles, porous silica, and mixtures thereof. In one aspect, one or more encapsulating materials are selected from cyclodextrins and mixtures thereof.

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

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

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

In one aspect, one or more cyclodextrins are selected from the group consisting of substituted (α)-cyclodextrin, substituted (β)-cyclodextrin, substituted (γ)-cyclodextrin, and mixtures thereof. In one aspect, one or more cyclodextrins are selected from substituted (β)-cyclodextrins. Chemical substitutions are preferred at the 2-, 3-, and 6-hydroxyl positions, with more preferred substitutions at the 2-position.

In one aspect, 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 aspect, one or more cyclodextrins are at least 2-hydroxypropyl-α-cyclodextrin. In one aspect, one or more cyclodextrins are at least 2-hydroxypropyl-β-cyclodextrin. In one aspect, one or more cyclodextrins are at least 2-hydroxypropyl-γ-cyclodextrin.

2-Hydroxypropyl derivatives of cyclodextrins such as 2-hydroxypropyl-β-cyclodextrin have increased water solubility compared to basic cyclodextrins such as β-cyclodextrin.

One or more cyclodextrins may or may not be present in any suitable amount in the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 12% by weight based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 10% by weight, based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 9% by weight based on the weight of the crystalline powder. In one aspect, the one or more cyclodextrins are present in a total amount of not more than 8% by weight based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 7% by weight based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 6% by weight based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 5% by weight, based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 4% by weight, based on the weight of the crystalline powder. In one aspect, one or more cyclodextrins are present in a total amount of not more than 3% by weight, based on the weight of the crystalline powder.

Way

In one aspect, a method is provided for preparing a gel containing

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) a water soluble acid;

moreover, this method includes the steps:

(a) providing a nicotine solution containing

(i) water in an amount of 50 to 90% by weight, based on the weight of the nicotine solution;

(ii) nicotine; as well as

(iii) a water soluble acid;

(b) dehydrogenating said nicotine solution to obtain a gel.

As discussed in the present description, in one aspect, a method is provided for obtaining a crystalline powder containing

(i) water in an amount of less than 15% by weight based on the weight of the crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

moreover, this method includes the steps:

(a) providing a nicotine solution containing

(i) water in an amount of 50 to 95% by weight, based on the weight of the nicotine solution;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

(b) dehydrogenating said nicotine solution to obtain a crystalline powder.

In one aspect, in a method for producing a gel, a nicotine solution is provided containing water in an amount of from 55 to 90 wt.% relative to the weight of the nicotine solution. In one aspect, in a method for producing a gel, a nicotine solution is provided containing water in an amount of 60 to 90% by weight relative to the weight of the nicotine solution. In one aspect, the gel preparation process provides a nicotine solution containing water in an amount of 65 to 90% by weight relative to the weight of the nicotine solution. In one aspect, in a method for producing a gel, a nicotine solution is provided containing water in an amount of 70 to 90% by weight relative to the weight of the nicotine solution. In one aspect, in a method for producing a gel, a nicotine solution is provided containing water in an amount of 75 to 90% by weight relative to the weight of the nicotine solution. In one aspect, the gel preparation process provides a nicotine solution containing water in an amount of 75 to 85% by weight relative to the weight of the nicotine solution.

In one aspect, in a method for producing a crystalline powder, a nicotine solution is provided containing water in an amount of from 55 to 95 wt.% relative to the weight of the nicotine solution. In one aspect, in a process for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 60 to 95% by weight relative to the weight of the nicotine solution. In one aspect, in a method for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 65 to 95% by weight relative to the weight of the nicotine solution. In one aspect, in a process for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 70 to 95% by weight relative to the weight of the nicotine solution. In one aspect, in a method for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 75 to 95% by weight relative to the weight of the nicotine solution. In one aspect, in a process for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 80 to 95% by weight relative to the weight of the nicotine solution. In one aspect, in a method for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 85 to 95% by weight relative to the weight of the nicotine solution. In one aspect, in a method for producing a crystalline powder, a nicotine solution is provided containing water in an amount of 90 to 95% by weight relative to the weight of the nicotine solution.

A typical method is described as follows.

During preparation, the composition is prepared, which is stirred and heated to approximately 40°C. This allows the components to be properly mixed throughout the entire process. At this temperature, cyclodextrin (such as (2-hydroxypropyl)-β-cyclodextrin) is thermally stable and must be added first. Generally, the maximum loading of 10% by weight should not be exceeded. This loading will depend on the percentage of flavor composition and is expected to be less to achieve 90% water incorporation.

The nicotine can then be added, bearing in mind that since it is already water-miscible, no precipitation will be observed. Typical loading ranges are from 0.1 to 1.2 wt%.

Flavoring components should be added last; this is due to the generally higher binding energy (compared to nicotine) with the cyclodextrin carrier. The inventors found that the greater the difference in binding energies, the less likely a competing mechanism of complex formation with nicotine would occur. For menthol, for example, the approximate binding energy is -4.13 kcal.mol ^-1 (nicotine) and -5.06 kcal.mol ^-1 (menthol). It should be noted that for this example, and depending on the load, a slight precipitation of menthol may be observed upon cooling from 40°C to ambient temperature. In this case, microfiltration can be performed to remove any excess menthol that has not complexed with the cyclodextrin.

An aqueous solution of citric acid and nicotine was prepared using a 1:1 molar equivalent ratio. The resulting liquid is bright orange and shows no signs of separation. With the help of a desiccator, water and any water-soluble impurities are removed from the liquid, resulting in a bright orange precipitate of a gel-like consistency. It can be called "nicotinium citrate" gel. The composition can then be prepared as above, except that no heating or filtration steps are required. When nicotinium citrate gel is added in place of nicotine in the final formulation steps, it dissociates into the corresponding nicotinium(+) and citrate(-) ions. Because nicotinium(+) is inherently larger than nicotine (it has inherited a proton from its corresponding citrate(-) ion), it does not interfere with the menthol-cyclodextrin complexation mechanism, since menthol is now the preferred guest compound. Thus, there is no visual precipitate of menthol. Perceptually, the composition is more stable if it is prepared in this way. Flavor delivery is optimized and no longer stops with increasing nicotine concentration. The delivery of nicotine is also optimized because the nicotine is now in the particulate phase rather than the vapor phase, so it can penetrate deep into the lungs. The presence of citrate(-) ions complements the properties of nicotine, providing the inherent bitterness and improving the "hook" of the throat. Due to this effect, a further decrease in the concentration of nicotine is possible.

Thus, in one aspect, a method is provided for preparing a crystalline powder containing

(i) water in an amount of less than 15% by weight based on the weight of the crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

moreover, this method includes the steps:

(a) providing a gel containing

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) water soluble acid

(b) providing a flavoring solution containing

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

bringing said gel into contact with said flavoring solution to form a nicotine solution; as well as

(c) dehydrogenating said nicotine solution to obtain a crystalline powder.

As discussed herein, in one aspect, a method is provided for rehydrating a gel containing

(i) water in an amount of 1 to 20% by weight based on the weight of the gel;

(ii) nicotine; as well as

(iii) a water soluble acid;

said method comprising the step of contacting said gel with water.

As discussed herein, in one aspect, a method is provided for rehydrating a crystalline powder containing

(i) water in an amount of less than 15% by weight based on the weight of the crystalline powder;

(ii) nicotine;

(iii) a water soluble acid;

(iv) one or more flavoring substances; as well as

(v) an encapsulating material;

wherein said method includes the step of contacting said crystalline powder with water.

The gel or crystalline powder may be placed in a container or delivered by any means. In one aspect, the present invention relates to a containerized gel or crystalline powder comprising (a) one or more containers; and (b) a gel or crystalline powder as defined herein. The container may be any suitable container, for example for storage or delivery of a gel or crystalline powder. In one aspect, the container is configured to interact with an electronic aerosol delivery system. The container may be configured to be in fluid communication with the electronic aerosol delivery system so that the gel or crystalline powder can be delivered to the electronic aerosol delivery system. As described above, the present invention relates to a container that can be used in an electronic aerosol delivery system such as an electronic cigarette. In the following description, the term "electronic cigarette" is used; however, the term may be used as a synonym for an electronic aerosol delivery system.

As discussed herein, the container of the present invention is typically designed to deliver a gel or crystalline powder to or within an electronic cigarette. The gel or crystalline powder may be stored inside the electronic cigarette or may be sold as a separate container for later use with or in the electronic cigarette. As one skilled in the art will appreciate, electronic cigarettes may comprise a unit known as a plug-in cartomizer, which typically includes a reservoir of gel or crystalline powder, a wick, and a heating element to vaporize the gel or crystalline powder. In some electronic cigarettes, the cartomizer is part of the whole device and is not removable. In one aspect, the container is a cartomizer or part of a cartomizer. In one aspect, the container is not a cartomizer or part of a cartomizer, but is a container, such as a reservoir, that can be used to deliver nicotine gel or crystalline powder to or within an electronic cigarette.

In one aspect, the container is part of an electronic cigarette. Therefore, in a further aspect, the present invention provides an electronic aerosol delivery system comprising: a gel or crystalline powder as defined herein; an aerosol generator for aerosolizing a gel or crystalline powder to be inhaled by a user of the electronic aerosol supply system; a power source containing a galvanic cell or battery, designed to supply the aerosol generator with energy.

In addition to the gel or crystalline powder of the present invention and systems such as containers and electronic aerosol delivery systems containing them, the present invention provides a method for improving the organoleptic properties of aerosolized nicotine. In a further aspect, the present invention provides a method for improving the storage stability of an aerosolized nicotine gel or crystalline powder.

Reference to improving the organoleptic properties of the vaporized nicotine solution may include improving the softness of the vaporized nicotine solution as perceived by the user.

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

Brief description of the drawings

The present invention will now be described in more detail by way of example only with reference to the accompanying figure, in which:

in fig. 1 is a graph illustrating the change in p _s K _a2 as a function of nicotine concentration.

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

Examples

Example 1

It was experimentally found that the solubility of the crystalline powder in isopropyl alcohol (IPA) was approximately 1 g/100 ml at 20°C after vigorous stirring. 20 ml of the crystalline powder extract was prepared in triplicate and analyzed for nicotine/menthol and water content by gas chromatography with a flame ionization detector (GC-FID).

N-heptadecane was added as an internal standard at 125 mg/ml to each extract for nicotine/menthol measurements, and ethanol (100%) was added as an internal standard at 125 mg/ml to each extract for water measurements.

Menthol was measured below the reported limit of 0.0747 mg/mL for all three samples. Two samples contained nicotine measured below the method limit of 0.0251 mg/mL.

Water was detected in all samples within the limits of the method calibration curve (0.00–0.09 mg/mL).

Example 2

Method for obtaining nicotinium citrate

Prepared 5 ml of an aqueous solution of 0.2044 g of citric acid and 0.2035 g of nicotine using a ratio of molar equivalents of 1:1. The resulting liquid was homogeneous and showed no signs of separation. No heating or filtration steps were required.

Dehydrogenation process

Using a desiccator and silica gel, water and any water-soluble impurities were removed from the liquid using vacuum for 24 hours, which led to the formation of a precipitate of a gel-like consistency. The resulting gel was dried in air overnight. It was called "nicotinium citrate" gel.

Combining nicotinium citrate with a flavoring agent

First, 10 ml of an aqueous solution was prepared by stirring 0.9% (w/w) menthol and 9% (w/w) 2-hydroxypropyl-β-cyclodextrin on a hot plate at 40° C. for about 30 minutes. Then, an aqueous solution containing a flavoring compound and an encapsulating material was added to the dried gel, and stirred to dissolve for another 30 minutes. The result was a homogeneous solution without any signs of segregation.

Method for obtaining crystalline powder

The resulting solution was then dried using the same dehydrogenation process for 1 week, resulting in a crystalline powder (solid) containing nicotine, flavor, encapsulating material, and ~7% (w/w) water. This powder was later rehydrated by simply adding water and mixing. After stirring for 3 minutes, the powder was completely rehydrated to give a clear solution.

For organoleptic testing, 1.5 g of the crystalline powder was dissolved in 10 ml of water by stirring for 3 minutes at room temperature. The solution provided was loaded into a commercially available nebulizer. The organoleptic perception of the rehydrated composition was assessed by the panel members as acceptable.

Various modifications and variations of the present invention will be understood by those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the claimed invention should not be unduly limited to such specific embodiments. Indeed, various modifications of the described methods of carrying out the invention, which are understood by a person skilled in the field of chemistry or related fields, are intended to be included in the scope of the following claims.

Claims (102)

1. Gel used to obtain a crystalline powder, containing: (i) water in an amount of 1 to 20% by weight based on the weight of the gel, (ii) nicotine; as well as (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20° C., while the molar ratio of acid to nicotine is from 3:1 to 1:3. 2. Gel according to claim. 1, characterized in that water is present in an amount of from 1 to 15 wt.% in relation to the mass of the gel. 3. Gel according to claim. 1 or 2, characterized in that water is present in an amount of from 1 to 10 wt.% in relation to the mass of the gel. 4. Gel according to claim. 1, 2 or 3, characterized in that nicotine is present in an amount of not more than 90 wt.% in relation to the mass of the gel. 5. Gel according to claim. 4, characterized in that nicotine is present in an amount of from 50 to 75 wt.% in relation to the mass of the gel. 6. Gel according to any one of paragraphs. 1-5, characterized in that the molar ratio of acid to nicotine is from 2:1 to 1:2. 7. Gel according to any one of paragraphs. 1-6, characterized in that 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 acids and their mixtures. 8. Gel according to any one of paragraphs. 1-7, characterized in that the water-soluble acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, lactic acid, sorbic acid and mixtures thereof. 9. Gel according to any one of paragraphs. 1-8, characterized in that the water-soluble acid is at least citric acid. 10. Crystalline powder used to obtain a solution for an aerosol supply device, containing: (i) water in an amount of less than 15 wt.% in relation to the mass of the crystalline powder; (ii) nicotine; (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20°C; (iv) one or more flavoring substances; as well as (v) an encapsulating material, while the molar ratio of acid to nicotine is from 3:1 to 1:3. 11. Crystalline powder according to claim 10, characterized in that nicotine is present in an amount of not more than 10 wt.% in relation to the mass of crystalline powder. 12. The crystalline powder according to claim 11, characterized in that nicotine is present in an amount of 1 to 3 wt.% relative to the mass of the crystalline powder. 13. Crystalline powder according to any one of paragraphs. 10-12, characterized in that water is present in an amount of less than 10 wt.% in relation to the mass of the crystalline powder. 14. Crystalline powder according to any one of paragraphs. 10-13, characterized in that water is present in an amount of less than 8 wt.% relative to the mass of the crystalline powder. 15. Crystalline powder according to any one of paragraphs. 10-14, characterized in that the molar ratio of acid to nicotine is from 2:1 to 1:2. 16. Crystalline powder according to any one of paragraphs. 10-15, characterized in that 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 acids and their mixtures. 17. Crystalline powder according to any one of paragraphs. 10-16, characterized in that the water-soluble acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, lactic acid, sorbic acid and mixtures thereof. 18. Crystalline powder according to any one of paragraphs. 10-17, characterized in that the water-soluble acid is at least citric acid. 19. Crystalline powder according to any one of paragraphs. 10-18, characterized in that the encapsulating material is one or more cyclodextrins. 20. The crystalline powder according to claim 19, characterized in that one or more cyclodextrins are selected from the group consisting of substituted or unsubstituted (α)-cyclodextrin, substituted or unsubstituted (β)-cyclodextrin, substituted or unsubstituted (γ)-cyclodextrin and their mixtures. 21. Crystalline powder according to claim 19 or 20, characterized in that one or more cyclodextrins are present in a total amount of not more than 85 wt.% in relation to the mass of crystalline powder. 22. Crystalline powder according to any one of paragraphs. 19-21, characterized in that one or more cyclodextrins are present in a total amount of 50 to 85 wt.% relative to the mass of the crystalline powder. 23. Crystalline powder according to any one of paragraphs. 10-22, characterized in that one or more flavoring substances are selected from the group consisting of (4-(para)methoxyphenyl)-2-butanone, vanillin, γ-undecalactone, menthone, 5-propenylguaethol, menthol, para-mentha- 8-thiol-3-one and mixtures thereof. 24. The crystalline powder according to claim 23, wherein the flavoring agent is at least menthol. 25. Crystalline powder according to any one of paragraphs. 23 or 24, characterized in that one or more flavoring substances are present in a total amount of not more than 2 wt.% in relation to the mass of the gel or crystalline powder. 26. Crystalline powder according to any one of paragraphs. 23-25, characterized in that one or more flavoring substances are present in a total amount of 0.01 to 1 wt.% relative to the mass of the gel or crystalline powder. 27. A method of obtaining a gel used to obtain a crystalline powder containing: (i) water in an amount of 1 to 20% by weight based on the weight of the gel; (ii) nicotine; as well as (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20° C., while the molar ratio of acid to nicotine is from 3:1 to 1:3; moreover, this method includes the steps: (a) providing a nicotine solution containing: (i) water in an amount of 50 to 90% by weight, based on the weight of the nicotine solution; (ii) nicotine; as well as (iii) said water-soluble acid; (b) dehydrogenating said nicotine solution to obtain a gel. 28. The method according to p. 27, characterized in that the gel is a gel, as defined in any of paragraphs. 2-9. 29. A method for obtaining a crystalline powder used to obtain a solution for an aerosol providing device, containing: (i) water in an amount of less than 15 wt.% in relation to the mass of the crystalline powder; (ii) nicotine; (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20°C; (iv) one or more flavoring substances; as well as (v) an encapsulating material, while the molar ratio of acid to nicotine is from 3:1 to 1:3; moreover, this method includes the steps: (a) providing a nicotine solution containing: (i) water in an amount of 50 to 95% by weight, based on the weight of the nicotine solution; (ii) nicotine; (iii) said water soluble acid; (iv) one or more flavoring substances; as well as (v) an encapsulating material; while the molar ratio of acid to nicotine is from 3:1 to 1:3; (b) dehydrogenating said nicotine solution to obtain a crystalline powder. 30. The method according to p. 29, characterized in that the crystalline powder is a crystalline powder, as defined in any of paragraphs. 10-26. 31. The method according to claim 29 or 30, wherein said method includes the steps of: (a) bringing the gel according to any one of paragraphs. 1-9 in contact with a flavoring solution containing: (iii) a water soluble acid; (iv) one or more flavoring substances; as well as (v) an encapsulating material; to obtain a nicotine solution; (b) dehydrogenating said nicotine solution to obtain a crystalline powder. 32. The method of rehydration of the gel used to obtain a crystalline powder containing: (i) water in an amount of 1 to 20% by weight based on the weight of the gel; (ii) nicotine; as well as (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20° C., while the molar ratio of acid to nicotine is from 3:1 to 1:3; said method comprising the step of contacting said gel with water. 33. Method for rehydration of crystalline powder to obtain a solution for an aerosol supply device, containing: (i) water in an amount of less than 15 wt.% in relation to the mass of the crystalline powder; (ii) nicotine; (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20°C; (iv) one or more flavoring substances; as well as (v) an encapsulating material; while the molar ratio of acid to nicotine is from 3:1 to 1:3; wherein said method includes the step of contacting said crystalline powder with water. 34. A containerized gel used to obtain a crystalline powder, containing: (a) a container; as well as (b) a gel containing: (i) water in an amount of 1 to 20% by weight based on the weight of the gel; (ii) nicotine; as well as (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20° C., while the molar ratio of acid to nicotine is from 3:1 to 1:3. 35. A crystalline powder enclosed in a container used to obtain a solution for an aerosol supply device, containing: (a) a container; as well as (b) a crystalline powder containing: (i) water in an amount of less than 15% by weight based on the weight of the crystalline powder; (ii) nicotine; (iii) a water-soluble acid having a solubility in water of at least 20 g/l at 20°C; (iv) one or more flavoring substances; as well as (v) an encapsulating material, while the molar ratio of acid to nicotine is from 3:1 to 1:3.

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