ES2984536T3 - Aerosolizable formulation - Google Patents

Abstract

An aerosolizable formulation is provided comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and (ii) nicotine. Also provided is a process for forming an aerosol, the process comprising aerosolizing an aerosolizable formulation comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and (ii) nicotine or one or more flavorings. (Automatic translation with Google Translate, no legal value)

Description

DESCRIPTION

Aerosolizable formulation

Field of invention

The present description relates to an aerosolizable formulation, a method of forming the same, a container containing it, a device containing it and processes and uses thereof.

Background of the invention

Electronic aerosol delivery systems, such as e-cigarettes, typically contain a reservoir of liquid to be vaporized, which usually contains nicotine. When a user inhales on the device, a heater is activated to vaporize a small amount of liquid, which is then inhaled by the user.

The use of e-cigarettes in the UK has grown rapidly, and it has been estimated that there are now more than one million people using them in the UK.

A challenge faced in providing such systems is providing from the aerosol delivery device an inhalable aerosol that provides consumers with an acceptable experience. Some consumers may prefer an e-cigarette that generates an aerosol that closely "mimics" the inhaled smoke from a tobacco product, such as a cigarette. E-cigarette aerosols and smoke from tobacco products, such as cigarettes, provide the user with a complex chain of taste 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 taste, intensity/quality, impact, irritation/smoothness, and nicotine reward. Nicotine contributes to a number of these factors, and is strongly associated with factors such as impact, irritation, and smoothness; these are readily perceived by consumers, and e-cigarettes may offer too much or too little of these parameters for consumers, depending on individual preferences. Nicotine reward is particularly complex, as it results from both the amount and rate at which nicotine is absorbed from the lining of the mouth, this is typically nicotine in the vapour phase, and the amount and rate at which nicotine is absorbed from the lungs, this is typically nicotine in the aerosol particle phase that is inhaled. Each of these factors, and their balance, can contribute greatly to the consumer acceptability of an e-cigarette. Therefore, providing means to optimise the overall vaping experience is desirable for e-cigarette manufacturers.

Another challenge facing these systems is the continuing demand for harm reduction. The harm from cigarettes and e-cigarette devices comes primarily from toxic substances. Therefore, there is a desire to reduce or eliminate components that can form toxicants.

US2004034068 A1 teaches a liquid pharmaceutical formulation comprising a nicotine salt and at least 90% by weight of water. The composition is supplied as an aerosol. DE102015117811 A1 describes an aqueous nicotine composition containing 85-99% by weight of water and thymol as a flavouring agent. It is supplied in the form of an aerosol.

Brief description of the invention

In one aspect, there is provided an aerosolizable formulation as defined in claim 1 comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and

(ii) nicotine.

In one aspect, there is provided an aerosolizable formulation as defined in claim 3 comprising (i) water in an amount of at least 95% by weight based on the aerosolizable formulation; and

(ii) nicotine.

In one aspect according to claim 9, there is provided a process for forming an aerosol, the process comprising aerosolizing an aerosolizable formulation comprising

(i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and

(ii) nicotine or one or more flavors.

In one aspect, there is provided a contained aerosolizable formulation as defined in claim 12 comprising (a) a container; and (b) an aerosolizable formulation, comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and (ii) nicotine.

In one aspect, there is provided an electronic aerosol delivery system as defined in claim 14 comprising: (a) an aerosolizer for aerosolizing the formulation for inhalation by a user of the electronic aerosol delivery system; (b) a power source comprising a cell or battery for supplying power to the aerosolizer; (c) an aerosolizable formulation, comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and (ii) nicotine or one or more flavors.

Detailed description of the invention

It has been discovered that an advantageous system can be provided in which an aerosolizable formulation containing a very high water content is used to deliver nicotine and/or flavor.

We have surprisingly found that very high water content provides a sensory perception to the user that is desirably close to the nicotine “hit” and/or flavor release provided by tobacco-based cigarettes. This desirable nicotine “hit” and/or flavor release is in contrast to “traditional” glycerol and propylene glycol-based e-liquids that users sometimes do not use due to perceived differences from the nicotine “hit” and/or flavor release provided by tobacco-based cigarettes.

We have also identified that a water-based system may be provided in which the aerosolised formulation is formed from an aerosolisable formulation at a low temperature. This is in contrast to 'traditional' e-cigarettes which use a heater, typically applied to glycerol and propylene glycol based liquids to form an aerosol formulation. The provision of such a system and the avoidance of heating may address prior art problems relating to the formation of toxic substances. More specifically, we have identified a water-based system which, by selecting a very high water content, provides desirable nicotine and/or flavour release, but avoids the need to use the heaters associated with prior glycerol and propylene glycol based liquids. In the present system, the number of components present may be reduced, leading to less chance of forming breakdown products/toxic substances. In particular, the use of water allows the replacement of part or all of the glycerol, propylene glycol, 1,3-propanediol and mixtures thereof typically used in electronic cigarettes.

For ease of reference, these and other aspects of the present invention are now discussed under appropriate section headings. However, the teachings of each section are not necessarily limited to that particular section.

Water

As discussed herein, the aerosolizable formulation comprises water in an amount of at least 85% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 87% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 89% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 91% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 93% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 95% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 97% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.1% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.2% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.3% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.4% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.5% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.6% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.7% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.8% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of at least 99.9% by weight based on the aerosolizable formulation.

In one aspect, the water is present in an amount of 85 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 90 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 92 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 94 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 95 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 96 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 97 to 99.9% by weight based on the aerosolizable formulation. In one aspect, the water is present in an amount of 98 to 99.9% by weight based on the aerosolizable formulation. in the aerosolizable formulation. In one aspect, water is present in an amount of 99 to 99.9% by weight based on the aerosolizable formulation.

As discussed herein, the use of water allows for the replacement of some or all of the glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof typically used in electronic cigarettes. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 10% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 8% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 1% by weight based on the aerosolizable formulation. In one embodiment, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 0.5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 0.2% by weight based on the aerosolizable formulation. In one embodiment, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 0.1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof in a combined amount of no more than 0.01% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation does not contain glycerol, propylene glycol, 1,3-propanediol, or mixtures thereof.

In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 10% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 8% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 0.5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 0.2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 0.1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no more than 0.01% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation does not contain glycerol, propylene glycol, or mixtures thereof.

In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 10% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 8% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 0.5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 0.2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 0.1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains glycerol in an amount of no greater than 0.01% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation does not contain glycerol.

In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 10% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 8% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 0.5% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 0.2% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 0.1% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation contains propylene glycol in an amount of no greater than 0.01% by weight based on the aerosolizable formulation. In one aspect, the aerosolizable formulation does not contain propylene glycol.

Acid

In one aspect, the aerosolizable formulation further comprises an acid. The acid may be any suitable acid. 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 consists of citric acid.

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

The acid may be present in any suitable amount. In one aspect, the acid is present in an amount of no more than 6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of no more than 4% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 4% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 4% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 4% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 4% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of no more than 3% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 3% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 3% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 3% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 3% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount no greater than 2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of no more than 1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.1 to 1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of no more than 0.6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 0.6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 0.6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 0.6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 0.6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.1 to 0.6% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of no more than 0.5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 0.5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 0.5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 0.5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 0.5% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount no greater than 0.2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 0.2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 0.2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 0.2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 0.2% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of no more than 0.1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.01 to 0.1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.02 to 0.1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.05 to 0.1% by weight based on the aerosolizable formulation. In one aspect, the acid is present in an amount of from 0.08 to 0.1% by weight based on the aerosolizable formulation.

In one aspect, the acid has a water solubility of at least 2 g/L at 20 °C. In one aspect, the acid has a water solubility of at least 5 g/L at 20 °C. In one aspect, the acid has a water solubility of at least 10 g/L at 20 °C. In one aspect, the acid has a water solubility 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.

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

In aspects of the invention in which nicotine is present, the molar ratio of acid to nicotine may be selected as desired. In one embodiment, the molar ratio of acid to nicotine is from 5:1 to 1:5. In one embodiment, the molar ratio of acid to nicotine is from 4:1 to 1:4. In one embodiment, the molar ratio of acid to nicotine is from 3:1 to 1:3. In one embodiment, the molar ratio of acid to nicotine is from 2:1 to 1:2. In one embodiment, the molar ratio of acid to nicotine is from 1.5:1 to 1:1.5. In one embodiment, the molar ratio of acid to nicotine is from 1.2:1 to 1:1.2. In one embodiment, the molar ratio of acid to nicotine is from 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 one embodiment, the molar ratio of acid to nicotine is 1.2:1 to 1:1.

In one aspect the total acid content present in the formulation is not greater than 5 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 4 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 3 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 2 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 1 equivalent mole based on nicotine.

In one aspect the total acid content present in the formulation is not greater than 0.01 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.05 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.1 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.2 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.3 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.4 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.5 equivalent moles based on nicotine. In one aspect the total acid content present in the formulation is not greater than 0.7 mol equivalents based on nicotine.

Nicotine

Nicotine formulations having desirable properties of taste, impact, irritation, smoothness, and/or nicotine reward to the user may be provided. In one aspect, nicotine is present in an amount of no more than 6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of no more than 4% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 4% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 4% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 4% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 4% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount no greater than 3% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 3% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 3% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 3% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 3% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount no greater than 2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of no more than 1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.1 to 1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of no more than 0.6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 0.6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 0.6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 0.6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 0.6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.1 to 0.6% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of no more than 0.5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 0.5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 0.5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 0.5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 0.5% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of no greater than 0.2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 0.2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 0.2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 0.2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 0.2% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of no greater than 0.1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.01 to 0.1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.02 to 0.1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.05 to 0.1% by weight based on the total weight of the aerosolizable formulation. In one aspect, nicotine is present in an amount of 0.08 to 0.1% by weight based on the total weight of the aerosolizable formulation.

As will be understood by one skilled in the art, nicotine may exist in an unprotonated form, a monoprotonated form, or a diprotonated form. The structures of each of these forms are given below.

deprotonated nicotine monoprotonated nicotine diprotonated nicotine

The reference in the specification to the protonated form means both monoprotonated and diprotonated nicotine. The reference in the specification to the amounts in protonated form means the combined amount of monoprotonated nicotine and diprotonated nicotine. In addition, where reference is made to a fully protonated formulation, it will be understood that at any one time there may be very small amounts of non-protonated nicotine present, for example less than 1% non-protonated nicotine.

In one aspect, the formulation may comprise nicotine in protonated form. In one aspect, the formulation may comprise nicotine in non-protonated form. In one aspect, the formulation comprises nicotine in non-protonated form and nicotine in monoprotonated form. In one aspect, the formulation comprises nicotine in non-protonated form and nicotine in diprotonated form. In one aspect, the formulation comprises nicotine in non-protonated form, nictoine in monoprotonated form, and nicotine in diprotonated form.

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

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

The relevant amounts of nicotine that are present in the formulation in protonated form are specified herein. These amounts can be readily calculated by one skilled in the art. Nicotine, 3-(1-methylpyrrolidin-2-yl)pyridine, is a diprotic base with pKa of 3.12 for the pyridine ring and 8.02 for the pyrrolidine ring. It can exist in pH-dependent protonated (mono- and diprotonated) and non-protonated (free base) forms that have different bioavailabilities.

The distribution of protonated and unprotonated nicotine will vary with varying increases in pH.

The fraction of unprotonated nicotine will be predominant at high pH levels, while as the pH decreases the fraction of protonated nicotine will increase (mono or di-depending on the pH). If the relative fraction 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 fraction of protonated nicotine in the formulation can be calculated using the Henderson-Hasselbalch equation, which describes pH as a derivation of the acid dissociation constant equation, and is widely used in chemical and biological systems. Consider the following equilibrium:

B H+ ^ BH+

The Henderson-Hasselbalch equation for this equilibrium is:

pH=pKa4- log- root

BH-h|

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

% protonated nicotine = 100

The determination of pKa values of nicotine formulations was carried out 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.

Flavor

As discussed herein, the aerosolizable formulation may comprise one or more flavors or flavoring components. As used herein, the terms "flavor" and "flavoring" refer to materials that, when permitted by local regulations, may be used to create a desired flavor or aroma in a product for adult consumers. They may include extracts (e.g. licorice, hydrangea, Japanese white bark, magnolia leaf, chamomile, fenugreek, clove, menthol, Japanese mint, anise, cinnamon, aromatic herb, wintergreen, cherry, blackberry, 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, sage, fennel, pepper, ginger, anise, coriander, coffee, or a mint oil of any species of the genus Mentha), flavor enhancers, bitter receptor blockers, sensory receptor activators or stimulators, sugars and/or sugar substitutes (e.g. sucralose, acesulfame potassium, aspartame, saccharin, cyclamates, lactose, sucrose, glucose, fructose, sorbitol or mannitol), and other additives such as charcoal, chlorophyll, minerals, botanicals or breath freshening agents. They may be imitation, synthetic or natural ingredients or mixtures thereof. They may be in any suitable form, for example, oil, liquid or powder. The one or more flavors may be selected from the group consisting of (4-(para-)methoxyphenyl)-2-butanone, vanillin, Y-undecalactone, menthone, 5-propenyl guaethol, menthol, para-mint-8-thiol-3-one and mixtures thereof. In one aspect the flavorant is at least menthol.

If present, the one or more flavors may be present in any suitable amount. In one aspect the one or more flavors are present in a total amount of no more than 10% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in a total amount of no more than 7% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in a total amount of no more than 5% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in a total amount of no more than 4% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in a total amount of no more than 3% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in a total amount of no more than 2% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in a total amount of no more than 1% by weight based on the aerosolizable formulation.

In one aspect the one or more flavors are present in an amount of from 0.01 to 5% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in an amount of from 0.01 to 4% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in an amount of from 0.01 to 3% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in an amount of from 0.01 to 2% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in an amount of from 0.01 to 1% by weight based on the aerosolizable formulation. In one aspect the one or more flavors are present in an amount of from 0.01 to 0.5% by weight based on the aerosolizable formulation.

Formulation

In one aspect, if the aerosolizable formulation contains one or more cyclodextrins, then the aerosolizable formulation does not contain flavors that can be encapsulated by the one or more cyclodextrins. In one aspect, if the aerosolizable formulation contains one or more cyclodextrins, then the aerosolizable formulation does not contain flavors.

As will be appreciated, the one or more cyclodextrins may or may not be present in any suitable amount in the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 12% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 10% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 9% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 8% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 7% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 6% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 5% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 4% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 3% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 2% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 1% by weight based on the aerosolizable formulation. In one embodiment, the one or more cyclodextrins are present in a total amount of no more than 0.1% by weight based on the aerosolizable formulation. In one aspect, the one or more cyclodextrins are present in a total amount of no more than 0.01% by weight based on the aerosolizable formulation. In one aspect, the one or more cyclodextrins are present in a total amount of no more than 0.001% by weight based on the aerosolizable formulation.

The aerosolizable formulation of the present invention comprises one or more cyclodextrins. The 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, the 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, the one or more cyclodextrins are selected from the group consisting of substituted cyclodextrins.

In one aspect, the one or more cyclodextrins are selected from the group consisting of (a)-unsubstituted cyclodextrin, (a)-substituted cyclodextrin, (p)-unsubstituted cyclodextrin, (p)-substituted cyclodextrin, (Y)-unsubstituted cyclodextrin, (y)-substituted cyclodextrin, and mixtures thereof. In one embodiment, the one or more cyclodextrins are selected from the group consisting of (p)-unsubstituted cyclodextrin, (p)-substituted cyclodextrin, and mixtures thereof.

In one embodiment, the one or more cyclodextrins are selected from the group consisting of (a)-unsubstituted cyclodextrin, (p)-unsubstituted cyclodextrin, (Y)-unsubstituted cyclodextrin, and mixtures thereof. In one embodiment, the one or more cyclodextrins are selected from (p)-unsubstituted cyclodextrin.

In one embodiment, the one or more cyclodextrins are selected from the group consisting of (a)-substituted cyclodextrin, (p)-substituted cyclodextrin, (Y)-substituted cyclodextrin, and mixtures thereof. In one embodiment, the one or more cyclodextrins are selected from substituted (p)-cyclodextrins. Chemical substitutions at the 2-, 3-, and 6-hydroxyl sites, and in particular substitution at the 2-position, are envisioned.

In one aspect, the one or more cyclodextrins are selected from the group consisting of 2-hydroxy-propyl-a-cyclodextrin, 2-hydroxy-propyl-p-cyclodextrin, 2-hydroxy-propyl-Y-cyclodextrin, and mixtures thereof. In one aspect, the one or more cyclodextrins is at least 2-hydroxy-propyl-a-cyclodextrin. In one aspect, the one or more cyclodextrins is at least 2-hydroxy-propyl-p-cyclodextrin. In one aspect, the one or more cyclodextrins is at least 2-hydroxy-propyl-Y-cyclodextrin.

2-Hydroxypropyl derivatives of cyclodextrins, such as 2-hydroxypropyl-p-cyclodextrin, have a higher water solubility compared to basic cyclodextrins such as p-cyclodextrin.

In further aspects, the aerosolizable formulation contains cyclodextrins in a total amount of no more than 0.001% by weight based on the aerosolizable formulation, such as cyclodextrins in a total non-weight amount based on the aerosolizable formulation, such as cyclodextrins in a total non-weight amount based on the aerosolizable formulation, such as cyclodextrins in a total non-weight amount based on the aerosolizable formulation. Thus, in further aspects, the present invention provides (1) an aerosolizable formulation comprising

(i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and

(ii) nicotine;

wherein the cyclodextrins are present in a total amount of up to 0.001% by weight based on the aerosolizable formulation.

(2) a process for forming an aerosol, the process comprising aerosolizing an aerosolizable formulation comprising

(i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and

(ii) nicotine or one or more flavors;

wherein the cyclodextrins are present in a total amount of up to 0.001% by weight based on the aerosolizable formulation.

(3) an aerosolizable formulation contained comprising

(a) a container; and

(b) an aerosolizable formulation, comprising

(i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and (ii) nicotine;

wherein the cyclodextrins are present in a total amount of up to 0.001% by weight based on the aerosolizable formulation.

(4) an electronic aerosol delivery system comprising:

(a) an aerosolizer for aerosolizing the formulation for inhalation by a user of the electronic aerosol delivery system;

(b) a power source comprising a cell or battery for supplying power to the aerosolizer (c) an aerosolizable formulation, comprising

(i) water in an amount of at least 85% by weight based on the aerosolizable formulation; and (ii) nicotine or one or more flavors;

wherein the cyclodextrins are present in a total amount of up to 0.001% by weight based on the aerosolizable formulation.

Process

In the process, the aerosol may be formed by a process carried out at a temperature below 60 °C. In the process, the aerosol may be formed by a process carried out at a temperature below 50 °C. In the process, the aerosol may be formed by a process carried out at a temperature below 40 °C. In the process, the aerosol may be formed by a process carried out at a temperature below 30 °C. In the process, the aerosol may be formed by a process carried out at a temperature below 25 °C. In the process, the aerosol may be formed by a process that does not involve heating.

In the process, aerosol can be formed by applying ultrasonic energy to the aerosolizable formulation.

In one aspect, the aerosol of the aerosolized formulation has a D50 of 2 to 6 µm. References herein to particle size distribution, D50, D10 or D90 refer to values measured in accordance with the British and European Pharmacopoeia, 2.9.31 Particle size analysis by laser light diffraction (see BRITISH PHARMACOPOEIA COMMISSION. (2014), British Pharmacopoeia. London, England: Stationery Office and COUNCIL OF EUROPE. (2013). European Pharmacopoeia. Strasbourg, France: Council of Europe). The terms D50, Dv50 and Dx50 are interchangeable. The terms D10, Dv10 and Dx10 are interchangeable. The terms D90, Dv90 and Dx9o are interchangeable.

In one aspect, the aerosol has a D50 of 2.5 to 6 µm. In one aspect, the aerosol has a D50 of 3 to 6 µm. In one aspect, the aerosol has a D50 of 3.5 to 6 µm. In one aspect, the aerosol has a D50 of 4 to 6 µm. In one aspect, the aerosol has a D50 of 4.5 to 6 µm. In one aspect, the aerosol has a D50 of 5 to 6 µm. In one aspect, the aerosol has a D50 of 2.5 to 5.5 µm. In one aspect, the aerosol has a D50 of 3 to 5.5 µm. In one aspect, the aerosol has a D50 of 3.5 to 5.5 µm.

In one aspect, the aerosol has a D50 of 4 to 5.5 µm. In one aspect, the aerosol has a D50 of 4.5 to 5.5 µm. In one aspect, the aerosol has a D50 of 5 to 5.5 µm.

In one aspect, the aerosol has a D10 of at least 0.5 jm. In one aspect, the aerosol has a D10 of at least 1 jm.

In one aspect, the aerosol has a D10 of at least 2 jm.

In one aspect, the aerosol has a D90 of no more than 15 µm. In one aspect, the aerosol has a D90 of no more than 12 µm. In one aspect, the aerosol has a D90 of no more than 10 µm.

In one aspect, D50 is measured after exclusion of particles having a particle size less than 1 µm. In one aspect, D10 is measured after exclusion of particles having a particle size less than 1 µm. In one aspect, D90 is measured after exclusion of particles having a particle size less than 1 µm.

The formulation may be contained or administered by any means. In one aspect, the present invention provides a contained aerosolizable formulation comprising (a) one or more containers; and (b) an aerosolizable formulation as defined herein. The container may be any suitable container, for example, to allow storage or delivery of the formulation. In one aspect, the container is configured for assembly with an electronic aerosol providing system. The container may be configured to be in fluid communication with an electronic aerosol delivery system such that the formulation may be delivered to the electronic aerosol delivery system. As described above, the present disclosure relates to a container that may be used in an electronic aerosol providing system, such as an electronic cigarette. Throughout the following description, the term "electronic cigarette" is used; however, this term may be used interchangeably with electronic aerosol providing system.

As discussed herein, the packaging of the present invention is typically provided for delivery of the aerosolizable formulation to or within an electronic cigarette. The aerosolizable formulation may be held within an electronic cigarette or may be sold as a separate packaging for later use with or in an electronic cigarette. As understood by one skilled in the art, electronic cigarettes may contain a unit known as a detachable cartomizer that typically comprises a reservoir of aerosolizable formulation, an aerosol such as a wick material, and a heating element for vaporizing the aerosolizable formulation. In some electronic cigarettes, the cartomizer is part of a single-piece device and is not detachable. In one aspect, the packaging is a cartomizer or part of a cartomizer. In one aspect, the packaging is not a cartomizer or part of a cartomizer and is a packaging, such as a reservoir, that can be used to deliver nicotine formulation to or within an electronic cigarette.

In one aspect, the packaging forms part of an electronic cigarette. Therefore, in a further aspect, the present invention provides an electronic aerosol delivery system comprising: an aerosolizable formulation as defined herein; an aerosolizer for aerosolizing the formulation for inhalation by a user of the electronic aerosol delivery system; and a power source comprising a cell or battery for supplying power to the aerosolizer.

The process of the present invention may comprise additional steps before the listed steps, 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:

Figure 1 shows a graph illustrating the variation of psKa<2> with nicotine concentration. The invention will now be described with reference to the following non-limiting examples.

Examples

Example 1 (not according to the invention)

A series of tests were conducted using commercially available vibrating mesh nebulizer devices. The "control" device was loaded with a formulation containing 90.0% (w/w) water, 8.8% (w/w) propylene glycol-containing flavoring, and 1.2% (w/w) nicotine.

A similar device was prepared in which 10.0% w/w glycerol was added to the formulation, with the water content reduced proportionally to 80.0% (w/w).

A similar device was prepared in which 10.0% w/w propylene glycol was added to the formulation, with the water content adjusted proportionally to 80.0% (w/w).

A similar device was prepared in which 5.0% w/w glycerol and 5.0% (w/w) propylene glycol were added to the formulation, with the water content adjusted proportionally to 80.0% (w/w).

A similar device was prepared in which 20.0% w/w glycerol was added to the formulation, with the water content reduced proportionally to 70.0% (w/w).

A similar device was prepared in which 20.0% w/w propylene glycol was added to the formulation, with the water content adjusted proportionally to 70.0% (w/w).

A similar device was prepared in which 10.0% w/w glycerol and 10.0% propylene glycol were added to the formulation, with the water content adjusted proportionally to 70.0% (w/w).

One of each of these devices was presented to 8 panelists comprising e-cigarette users, and the panelists were asked to inhale the devices monadicly sequentially for 5 puffs on each device. Each panelist was asked to choose a palatable flavour of their choice to aid feedback regarding the water, glycerol and propylene glycol composition. 8 panelists preferred the formulations that did not contain propylene glycol or glycerol at a concentration greater than 10.0% (w/w). 5 individuals preferred the formulation in the control device and 3 individuals preferred the formulation with 10% glycerol.

Example 2, whereby formulations 4-6 are not in accordance with the invention

Three Amaretto flavoured and three unflavoured formulations were blindly evaluated by up to 9 panelists, who are experienced vapers with varying tolerances to nicotine. During the sensory evaluation, the panelists rated various sensory attributes, such as throat irritation and chest impact, from low (1) to high (9). The panelists were also asked to indicate the most favourite formulation among those tested. A series of tests were conducted using commercially available vibrating mesh nebuliser devices.

The devices were loaded with formulations containing

Formulation 1 - 82% (w/w) water, 9.4% (w/w) 2-hydroxy-propyl-p-cyclodextrin, 8% (w/w) glycerol and 0.6% (w/w) nicotine.

Formulation 2 - 85% (w/w) water, 9.4% (w/w) 2-hydroxy-propyl-p-cyclodextrin, 5% (w/w) glycerol and 0.6% (w/w) nicotine.

Formulation 3 - 87% (w/w) water, 9.4% (w/w) 2-hydroxy-propyl-p-cyclodextrin, 3% (w/w) glycerol and 0.6% (w/w) nicotine.

Formulation 4 - 82% (w/w) water, 2.0% (w/w) propylene glycol containing amaretto flavor, 9.8% (w/w) glycerol, 5% (w/w) ethanol, 0.6% (w/w) nicotine and 0.6% (w/w) citric acid.

Formulation 5 - 85% (w/w) water, 2.0% (w/w) propylene glycol containing amaretto flavor, 6.8% (w/w) glycerol, 5% (w/w) ethanol, 0.6% (w/w) nicotine and 0.6% (w/w) citric acid.

Formulation 6 - 87% (w/w) water, 2.0% (w/w) propylene glycol containing amaretto flavor, 4.8% (w/w) glycerol, 5% (w/w) ethanol, 0.6% (w/w) nicotine and 0.6% (w/w) citric acid.

The summary of the tested formulations is presented in the table below.

5 of 7 panelists preferred an unflavored formulation with a water content of 85% (w/w), 1 of 7 panelists preferred an unflavored formulation with a water content of 87% (w/w), while only 1 panelist preferred an unflavored formulation with a water content of 82% (w/w).

8 out of 9 panelists preferred the Amaretto flavoured formulation with a water content of 85% and 87% (w/w), while only 1 panelist preferred the Amaretto flavoured formulation with a water content of 82% (w/w).

Claims (15)

1. An aerosolizable formulation comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; (ii) nicotine; and (iii) one or more cyclodextrins, wherein the aerosolizable formulation contains no flavors or does not contain flavors that can be encapsulated by the one or more cyclodextrins. 2. An aerosolizable formulation according to claim 1, wherein the water is present in an amount of at least 90% by weight based on the aerosolizable formulation, such as where the water is present in an amount of at least 95% by weight based on the aerosolizable formulation. 3. An aerosolizable formulation according to claim 1, comprising water in an amount of at least 95% by weight based on the aerosolizable formulation. 4. An aerosolizable formulation according to any one of claims 1 to 3, wherein water is present in an amount of at least 99% by weight based on the aerosolizable formulation. 5. An aerosolizable formulation according to any one of claims 1 to 4, wherein the nicotine is present in an amount of no more than 1% by weight based on the aerosolizable formulation, such as wherein the nicotine is present in an amount of 0.01 to 0.6% by weight based on the aerosolizable formulation. 6. An aerosolizable formulation according to any one of claims 1 to 5, wherein the aerosolizable formulation further comprises an acid, such as wherein 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, such as wherein the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, sorbic acid, lactic acid and mixtures thereof, such as wherein the acid is at least citric acid. 7. An aerosolizable formulation according to claim 6, wherein the total acid content present in the formulation is not greater than 1 molar equivalent based on nicotine, such as where the total acid content present in the solution is not less than 0.1 molar equivalent based on nicotine. 8. An aerosolizable formulation according to any one of claims 1 to 7 further comprising one or more flavors, such as wherein the one or more flavors are selected from the group consisting of (4-(para-)methoxyphenyl)-2-butanone, vanillin, Y-undecalactone, menthone, 5-propenyl guaethol, menthol, para-menthol-8-thiol-3-one and mixtures thereof, such as wherein the flavor is at least menthol, and/or wherein the one or more flavors are present in a total amount of not more than 2% by weight based on the aerosolizable formulation, such as wherein the one or more flavors are present in a total amount of 0.01 to 1% by weight based on the aerosolizable formulation. 9. A process for forming an aerosol, the process comprising aerosolizing an aerosolizable formulation comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; (ii) nicotine or one or more flavors; and (iii) one or more cyclodextrins, where the aerosolizable formulation does not contain flavors that can be encapsulated by the one or more cyclodextrins. 10. A process according to claim 9, wherein the aerosolizable formulation comprises nicotine and, optionally, one or more flavors. 11. A process according to claim 9 or 10, wherein the aerosol is formed by a process carried out at a temperature below 50 °C, such as where the aerosol is formed by applying ultrasonic energy to the aerosolizable formulation. 12. An aerosolizable formulation contained comprising (a) a container; and (b) an aerosolizable formulation, comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; (ii) nicotine; and (iii) one or more cyclodextrins, wherein the aerosolizable formulation contains no flavors or does not contain flavors that can be encapsulated by the one or more cyclodextrins. 13. An aerosolizable formulation contained according to claim 12, wherein the container is configured to couple with an electronic aerosol delivery system. 14. An electronic aerosol delivery system comprising: (a) an aerosolizer for aerosolizing the formulation for inhalation by a user of the electronic aerosol delivery system; (b) a power supply comprising a cell or battery for supplying power to the aerosolizer (c) an aerosolizable formulation, comprising (i) water in an amount of at least 85% by weight based on the aerosolizable formulation; (ii) nicotine or one or more flavors; and (iii) one or more cyclodextrins, where the aerosolizable formulation does not contain flavors that can be encapsulated by the one or more cyclodextrins. 15. An electronic aerosol delivery system according to claim 14, wherein the aerosolizable formulation comprises nicotine and, optionally, one or more flavors.