CN113015444A

CN113015444A - Aerosol formulation

Info

Publication number: CN113015444A
Application number: CN201980075317.2A
Authority: CN
Inventors: 罗斯·卡伯特
Original assignee: Nicoventures Trading Ltd
Current assignee: Nicoventures Trading Ltd
Priority date: 2018-11-01
Filing date: 2019-10-31
Publication date: 2021-06-22
Also published as: AU2019371079A1; GB201817865D0; IL282523A; MX2021005123A; EP4353091A2; AU2019371079B2; WO2020089637A1; EP3873245B1; BR112021008556A2; JP2022506094A; US20210386110A1; CA3118051A1; EP3873245A1; UA128040C2; KR20210075107A

Abstract

Provided is an aerosolizable formulation comprising (i) water in an amount of at least 85 wt.%, based on the aerosolizable formulation; and (ii) nicotine. Also provided is a method for forming an aerosol, the method comprising aerosolizing an aerosolizable formulation comprising (i) water in an amount of at least 85 wt.%, based on the aerosolizable formulation; and (ii) nicotine or one or more flavoring agents.

Description

Aerosol formulation

Technical Field

The present invention relates to aerosolizable formulations, methods of forming the same, containers comprising the same, devices comprising the same, and methods and uses thereof.

Background

An electronic aerosol provision system, such as an electronic cigarette, typically comprises a reservoir of liquid to be vaporised, typically comprising nicotine. When the user inhales on the device, the heater is activated to vaporise a small amount of liquid which is then inhaled by the user.

The use of e-cigarettes has increased rapidly in the uk and it is estimated that over one million people are now using e-cigarettes in the uk.

One challenge facing providing such a system is providing the aerosol to be inhaled from the aerosol provision device, which provides an acceptable experience for the consumer. Some consumers may prefer an e-cigarette that produces an aerosol that "closely simulates" the smoke inhaled from a tobacco product, such as a cigarette. Aerosols from electronic cigarettes, as well as smoke from tobacco products (such as cigarettes), provide users with a complex flavor chain in the mouth, with nicotine absorbed in the mouth and throat, followed by nicotine absorption in the lungs. These various aspects are described by the user in terms of flavor, intensity/quality, impact, irritation/smoothness, and nicotine return (reward). Nicotine contributes to many of these factors and is closely related to factors such as shock, irritation, and smoothness; these are easily perceived by the consumer and the e-cigarette may provide more or less of these parameters to the consumer according to personal preferences. Nicotine return is particularly complex because it is caused by the amount and rate of nicotine absorption from the oral cavity membrane (lining), which is typical of nicotine in the gas phase, and from the lungs, which is typical of nicotine in the particulate phase of the inhaled aerosol. Each of these factors and their balance may greatly contribute to consumer acceptance of e-cigarettes. Therefore, there is a need for e-cigarette manufacturers to provide a means to optimize the overall e-cigarette (vaping) experience.

A further challenge facing such systems is the continuing need to reduce hazards. Hazards from cigarettes and electronic cigarette devices come primarily from poisons. Accordingly, it is desirable to reduce or remove components that may form poisons.

Disclosure of Invention

In one aspect, an aerosolizable formulation is provided comprising

(i) Water in an amount of at least 85 wt.%, based on the aerosolizable formulation; and

(ii) nicotine. In this regard, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation may be free of flavors capable of being encapsulated by the one or more cyclodextrins.

In one aspect, an aerosolizable formulation is provided comprising

(i) Water in an amount of at least 95 wt.%, based on the aerosolizable formulation; and

(ii) nicotine.

In one aspect, a method for forming an aerosol is provided that includes aerosolizing an aerosolizable formulation comprising

(ii) nicotine or one or more flavoring agents. In this regard, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation may be free of flavors capable of being encapsulated by the one or more cyclodextrins.

(ii) nicotine.

In one aspect, an aerosolizable formulation is provided comprising (a) a container; and (b) an aerosolizable formulation comprising (i) water in an amount of at least 85 wt.%, based on the aerosolizable formulation; and (ii) nicotine. In this regard, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation may be free of flavors capable of being encapsulated by the one or more cyclodextrins.

In one aspect, an aerosolizable formulation is provided comprising, including

(a) A container; and

(b) an aerosolizable formulation comprising

(ii) nicotine.

In one aspect, there is provided an electronic aerosol provision system comprising: (a) an atomizer for aerosolizing a formulation for inhalation by a user of the electronic aerosol provision system; (b) a power supply comprising a unit or battery for supplying power to the atomizer; (c) an aerosolizable formulation comprising (i) water in an amount of at least 85 wt.%, based on the aerosolizable formulation; and (ii) nicotine or one or more flavoring agents. In this regard, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation may be free of flavors capable of being encapsulated by the one or more cyclodextrins.

In one aspect, there is provided an electronic aerosol provision system comprising:

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

(b) a power supply comprising a unit or battery for supplying power to the atomizer;

(c) an aerosolizable formulation comprising

(ii) nicotine.

Detailed Description

As discussed herein, there is provided an aerosolizable formulation comprising (i) water in an amount of at least 85 wt.%, based on the aerosolizable formulation; and (ii) nicotine. Also provided is a method for forming an aerosol, the method comprising aerosolizing an aerosolizable formulation comprising:

(ii) nicotine or one or more flavoring agents.

It has been found that an advantageous system can be provided wherein the aerosolizable formulation comprises a very high level of water and is used to deliver nicotine and/or flavors.

It has surprisingly been found that very high water content provides the user with a sensory perception that desirably approximates the nicotine "shock" and/or flavor release provided by tobacco-based cigarettes. This desirable nicotine "shock" and/or flavor release is in contrast to "traditional" e-liquids based on glycerin and propylene glycol, which are sometimes not used by users due to the perceived differences in nicotine "shock" and/or flavor release provided by tobacco-based cigarettes.

It has also been determined that it is possible to provide an aqueous-based system in which the aerosolized formulation is formed from an aerosolizable formulation at low temperatures. This is in contrast to "traditional" electronic cigarettes that use heaters that are typically applied to glycerin and propylene glycol based liquids to form aerosolized formulations. Providing such a system and avoiding heating may solve the problems associated with the formation of poisons of the prior art. More specifically, water-based systems have been identified that deliver the desired nicotine "shock" and/or flavor release by selecting very high water contents, but avoid the need for the use of heaters associated with prior art liquids based on glycerin and propylene glycol. In the system of the invention, the number of components present can be reduced, resulting in less chance of forming decomposition products/poisons. In particular, the use of water allows to replace some 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 will now be discussed under appropriate section headings. However, the teachings under each section are not necessarily limited to each particular section.

Water (W)

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

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

As discussed herein, the use of water allows for the replacement of some or all of the glycerin, propylene glycol, 1, 3-propanediol, and mixtures thereof typically used in electronic cigarettes. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 10 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 8 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 5 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 2 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 1 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 0.5 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 0.2 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 0.1 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, 1, 3-propanediol, and mixtures thereof in a total amount of no more than 0.01 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation is free of glycerin, propylene glycol, 1, 3-propanediol, and mixtures thereof.

In one aspect, the aerosolizable formulation comprises no more than 10 wt.% of glycerol, propylene glycol, and mixtures thereof, in total, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 8 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 5 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 2 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 1 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 0.5 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 0.2 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 0.1 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol, propylene glycol, and mixtures thereof in a total amount of no more than 0.01 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation is free of glycerin, propylene glycol, and mixtures thereof.

In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 10 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 8 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 5 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 2 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 1 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 0.5 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 0.2 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 0.1 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises glycerol in an amount of no more than 0.01 wt.% based on the aerosolizable formulation. In one aspect, the aerosolizable formulation is free of glycerin.

In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 10 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 8 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 5 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 2 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 1 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 0.5 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 0.2 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 0.1 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation comprises propylene glycol in an amount of no more than 0.01 wt.%, based on the aerosolizable formulation. In one aspect, the aerosolizable formulation is free of propylene glycol.

Acid(s)

In one aspect, the aerosolizable formulation further comprises an acid. The acid can 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 (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 2 to 5. In one aspect, the acid is a weak acid. In one aspect, the acid is a weak organic acid.

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

In one aspect, the acid has a solubility in water of at least 2g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 5g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 10g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 20g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 50g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 100g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 200g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 300g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 400g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 500g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 600g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 700g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 800g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 900g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 1000g/L at 20 ℃. In one aspect, the acid has a solubility in water of at least 1100g/L at 20 ℃.

The amount of acid and the solubility of the acid can be selected such that a given amount of acid will dissolve in water. In one aspect, at least 20% of the acid is dissolved in water at 20 ℃. In one aspect, at least 20% of the acid is dissolved in water at 25 ℃. In one aspect, at least 20% of the acid is dissolved in water at 30 ℃. In one aspect, at least 35% of the acid is dissolved in water at 20 ℃. In one aspect, at least 40% of the acid is dissolved in water at 20 ℃. In one aspect, at least 45% of the acid is dissolved in water at 20 ℃. In one aspect, at least 50% of the acid is dissolved in water at 20 ℃. In one aspect, at least 55% of the acid is dissolved in water at 20 ℃.

In aspects of the invention where nicotine is present, the molar ratio of acid to nicotine may 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 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 1.5:1 to 1: 1.5. In one aspect, the molar ratio of acid to nicotine is 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 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 1.5:1 to 1:1. In one aspect, the molar ratio of acid to nicotine is 1.2:1 to 1:1.

In one aspect, the total amount of acid present in the formulation does not exceed 5 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation does not exceed 4 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation does not exceed 3 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation does not exceed 2 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation does not exceed 1 molar equivalent based on nicotine.

In one aspect, the total amount of acid present in the formulation is not less than 0.01 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.05 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.1 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.2 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.3 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.4 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.5 molar equivalents based on nicotine. In one aspect, the total amount of acid present in the formulation is not less than 0.7 molar equivalents based on nicotine.

Nicotine

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

As understood by one of ordinary skill in the art, nicotine may exist in an unprotonated form, a monoprotonated form, or a biprotonated form. The structure of each of these forms is given below.

References to protonated forms in this specification refer to both monoprotized nicotine and biprotized nicotine. Reference in this specification to an amount in protonated form refers to the combined amount of monoprotized nicotine and diprotized nicotine. Furthermore, when referring to fully protonated formulations, it will be understood that very small amounts of unprotonated nicotine may be present at any one time, e.g., less than 1% unprotonated.

In one aspect, the formulation may include nicotine in a protonated form. In one aspect, the formulation may include nicotine in an unprotonated form. In one aspect, the formulation includes nicotine in an unprotonated form and nicotine in a monoprotonated form. In one aspect, the formulation includes nicotine in an unprotonated form and nicotine in a diprotonated form. In one aspect, the formulation includes nicotine in an unprotonated form, nicotine in a monoprotonated form, and nicotine in a diprotonated form.

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

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

The relative amount of nicotine present in protonated form in the formulations is identified herein. These amounts can be readily calculated by one skilled in the art. Nicotine, 3- (1-methylpyrrolidin-2-yl) pyridine, is a aprotic base with a pKa of 3.12 for the pyridine ring and 8.02 for the pyrrolidine ring. It can exist in pH-dependent (mono-and di-) protonated and unprotonated (free base) forms with different bioavailability.

The distribution of protonated and unprotonated nicotine will vary at different pH increments.

The proportion of unprotonated nicotine will dominate at high pH levels, whereas the proportion of protonated nicotine will increase with decreasing pH (mono-or bi-protonation, depending on pH). If the relative proportion of protonated nicotine and the total amount of nicotine in the sample is known, the absolute amount of protonated nicotine can be calculated.

The relative proportion of protonated nicotine in a formulation can be calculated by using the Henderson-Hasselbalch equation, which describes pH as the derivative of the acid dissociation constant equation, and which is widely used in chemical and biological systems. Consider the following balance:

the Henderson-Hasselbalch equation for this balance 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 reference pKa value for the pyrrolidine ring nitrogen of nicotine (pKa ═ 8.02). The relative proportion of protonated nicotine may be derived from the alpha value of unprotonated nicotine, calculated according to the Henderson-Hasselbalch equation:

the determination of the pKa values of nicotine formulations is carried out using the basic method described in "Spectroscopic studies of acid-base properties of nicotine at different temperatures" (Spectroscopic improvements of nicotine at differential temperatures) ", Peter M, Clayton, Carl A.vas, Tam T.T.Bui, Alex F.Drake and Kevin McAam, anal. methods, 2013, 5, 81-88.

Flavouring agent

As discussed herein, the aerosolizable formulation can include one or more flavoring agents or flavor components. As used herein, the terms "flavor" and "aroma" refer to materials that can be used to generate a desired taste or aroma in products of adult consumers as permitted by local regulations. They may include extracts (e.g., licorice (liquorice), hydrangea (hydrangea), Japanese white bark magnolia leaf (Japanese white bark woody leaf), chamomile (chamomile), fenugreek (fenugreek), clove (clover), menthol, Japanese mint, anise (aniseed), cinnamon (cinmamon), vanilla (herb), wintergreen, cherry, berry, peach, apple, Drambuie, bourbon (bourbon), scotch (scotch), whisky, spearmint (spirm), peppermint, lavender (lavender), cardamom (cardamom), celery (celery), salicyl (cascarilla), nutmeg (nutmeg), sandalwood (sandwood), bergamot (bergamot), geranium (orange oil, rose (jasmine oil), honey (jasmine oil), orange oil (sesame oil), cassia oil (orange oil), olive (orange oil), cinnamon (cinnamon), peppermint (cinnamon), cassia (cinnamon (black bayberry), olive (orange oil (cinnamon), cinnamon (cinnamon), olive (orange oil (black bayberry oil), black bayberry (black bayberry oil), black bayberry oil (black bayberry oil, Sage (fennel), fennel (piment), ginger, fennel (orange), coriander (coriander), coffee or peppermint oil from any species of the genus mentha), flavor enhancers, bitter taste receptor site blockers, sensory receptor site activators or stimulators, sugars and/or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives (such as charcoal, chlorophyll, minerals, botanicals, or odor fresheners). They may be imitations, synthetic or natural ingredients or mixtures thereof. They may be in any suitable form, for example oil, liquid or powder. The one or more flavoring agents are selected from the group consisting of: (4- (p-) methoxyphenyl) -2-butanone, vanillin, gamma undecalactone, menthone, 5-propenylethylguaiacol (5-propenylguaethol), menthol, p-mentha-8-thiol-3-one (para-mentha-8-thiol-3-one), and mixtures thereof. In one aspect, the flavoring agent is at least menthol.

If present, the one or more flavoring agents can be present in any suitable amount. In one aspect, the one or more flavoring agents are present in a total amount of no more than 10 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavorings are present in a total amount of no more than 7 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of no more than 5 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavorings are present in a total amount of no more than 4 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavorings are present in a total amount of no more than 3 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavorings are present in a total amount of no more than 2 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of no more than 1 wt.%, based on the aerosolizable formulation.

In one aspect, the one or more flavoring agents are present in a total amount of 0.01 to 5 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of 0.01 to 4 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of 0.01 to 3 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of 0.01 to 2 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of 0.01 to 1 wt.%, based on the aerosolizable formulation. In one aspect, the one or more flavoring agents are present in a total amount of 0.01 to 0.5 wt.%, based on the aerosolizable formulation.

Formulations

In one aspect, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation is free of flavors capable of being encapsulated by the one or more cyclodextrins. In one aspect, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation is free of flavoring.

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

The aerosolizable formulations of the present invention can comprise 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 cyclodextrin. In one aspect, the at least one cyclodextrin is a substituted cyclodextrin. In one aspect, the one or more cyclodextrins are selected from the group consisting of: a substituted cyclodextrin.

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

In one aspect, the 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, the one or more cyclodextrins are selected from unsubstituted (β) -cyclodextrins.

In one aspect, the one or more cyclodextrins are selected from the group consisting of: substituted (α) -cyclodextrins, substituted (β) -cyclodextrins, substituted (γ) -cyclodextrins, and mixtures thereof. In one aspect, the one or more cyclodextrins are selected from substituted (β) -cyclodextrins. Chemical substitutions at the 2-, 3-, and 6-hydroxy positions are contemplated, and in particular substitutions at the 2-position.

In one aspect, the one or more cyclodextrins are selected from the group consisting of: 2-hydroxy-propyl-alpha-cyclodextrin, 2-hydroxy-propyl-beta-cyclodextrin, 2-hydroxy-propyl-gamma-cyclodextrin, and mixtures thereof. In one aspect, the one or more cyclodextrins are at least 2-hydroxy-propyl-alpha-cyclodextrin. In one aspect, the one or more cyclodextrins are at least 2-hydroxy-propyl- β -cyclodextrin. In one aspect, the one or more cyclodextrins are at least 2-hydroxy-propyl- γ -cyclodextrin.

2-hydroxy-propyl derivatives of cyclodextrins (such as 2-hydroxy-propyl-beta-cyclodextrin) have increased solubility in water when compared to the base cyclodextrin (such as beta-cyclodextrin).

In other aspects, the aerosolizable formulation comprises no more than 0.001 wt.% of a cyclodextrin in a total amount, based on the aerosolizable formulation, such as no more than 1x10 in a total amount, based on the aerosolizable formulation^-4wt.% of cyclodextrin, such as, based on the aerosolizable formulation, no more than 1x10 in total^-5wt.% of cyclodextrin, such as, based on the aerosolizable formulation, no more than 1x10 in total^-6wt.% cyclodextrin. Thus, in a further aspect, the invention provides

(1) An aerosolizable formulation comprising

(ii) nicotine;

wherein the cyclodextrin is present in a total amount of 0 to 0.001 wt.%, based on the aerosolizable formulation.

(2) A method for forming an aerosol, the method comprising aerosolizing an aerosolizable formulation comprising:

(ii) nicotine or one or more flavoring agents;

(3) An aerosolizable formulation comprising

(a) A container; and

(b) an aerosolizable formulation comprising

(ii) nicotine;

(4) An electronic aerosol provision system comprising:

(c) an aerosolizable formulation comprising

(ii) nicotine or one or more flavoring agents;

Method

As discussed herein, in one aspect, there is provided a method for forming an aerosol, the method comprising aerosolizing an aerosolizable formulation comprising:

(ii) nicotine or one or more flavoring agents.

In a further aspect, a method for forming an aerosol is provided, the method comprising aerosolizing an aerosolizable formulation comprising

(ii) nicotine.

In this method, the aerosol may be formed by a process carried out at a temperature of less than 60 ℃. In this method, the aerosol may be formed by a process carried out at a temperature of less than 50 ℃. In this method, the aerosol may be formed by a process carried out at a temperature below 40 ℃. In this method, the aerosol may be formed by a process carried out at a temperature of less than 30 ℃. In this method, the aerosol may be formed by a process carried out at a temperature of less than 25 ℃. In this method, the aerosol may be formed by a process that does not involve heating.

In this method, an aerosol may be formed by applying ultrasonic energy to an aerosolizable formulation.

In one aspect, the aerosol of the aerosolized formulation has a D50 of 2 to 6 μm. Reference in this specification to Particle Size distribution D50, D10 or D90 refers to values measured By Particle Size Analysis By Laser Diffraction (Particle Size Analysis By Laser Light Diffraction) according to British and European PHARMACOPOEIA 2.9.31 (see BRITISH PHARMACOPOEIA COMMISON. (2014), British Pharmacopeia.London, England: static Office and COUNCIL OF EUROPE. (2013). Europan Pharmacopeia.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 Dx90 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 μm. In one aspect, the aerosol has a D10 of at least 1 μm. In one aspect, the aerosol has a D10 of at least 2 μm.

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

The formulation may be contained or delivered by any means. In one aspect, the present invention provides an aerosolizable formulation for inclusion, 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 to interface with an electronic aerosol provision system. The container may be configured to become in fluid communication with the electronic aerosol provision system such that the formulation may be delivered to the electronic aerosol provision system. As described above, the present disclosure relates to a container that may be used in an electronic aerosol provision system (such as an electronic cigarette). Throughout the following description, the term "electronic cigarette" is used; however, the term may be used interchangeably with the electronic aerosol provision system.

As discussed herein, the container of the present invention is generally provided for delivery of an aerosolizable formulation to or within an electronic cigarette. The aerosolizable formulation can be held within the electronic cigarette, or can be sold as a separate container for subsequent use with or in an electronic cigarette. As understood by those skilled in the art, an e-cigarette may comprise a unit known as a removable cartridge (cartomiser), which typically includes a reservoir of an aerosolizable formulation, an atomizer, such as a wick material, and a heating element for vaporizing the aerosolizable formulation. In some electronic cigarettes, the cartridge is part of a single piece device and is not removable. In one aspect, the container is or is part of a cartridge. In an aspect, the container is not a cartridge or part of a cartridge and is a container, such as a canister, that can be used to deliver nicotine formulation to or within an electronic cigarette.

In one aspect, the container is part of an electronic cigarette. Accordingly, in a further aspect, the present invention provides an electronic aerosol provision system comprising: an aerosolizable formulation as defined herein; an atomizer for atomizing the formulation for inhalation by a user of the electronic aerosol provision system; and a power supply comprising a unit or battery for supplying power to the atomizer.

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

Drawings

The invention will now be described in further detail, by way of example only, with reference to the following drawings, in which: -

FIG. 1 shows an illustration p_sK_a2Graph of variation with nicotine concentration.

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

Examples

Example 1

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

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

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

Each of these devices was presented to 8 panelists, including the e-cigarette user, and the panelists were asked to draw (puff) on the device in a sequential, one-time fashion (sequential monoadic washin), 5 puffs on each device. Each panelist was asked to select their chosen palatable flavor to aid in feedback on water, glycerin and propylene glycol composition.

The 8 panelists preferably did not contain formulations of propylene glycol or glycerol at concentrations above 10.0% (w/w). 5 persons prefer the formulation in the control device, and 3 persons prefer the formulation with 10% glycerin.

Example 2

Three almond (Amaretto) flavored and three non-flavored formulations were blindly evaluated by up to 9 panelists who were experienced smokers (vaper) with varying nicotine tolerance. During sensory evaluation, panelists rated several sensory attributes, such as throat irritation and chest impact, from low (1) to high (9). Panelists were also asked to indicate the most advantageous formulation in the test. A series of tests were performed using a commercially available vibrating mesh nebulizer apparatus.

These devices were loaded with formulations containing:

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

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

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

Preparation 4-82% (w/w) water, 2.0% (w/w) propylene glycol with almond flavour, 9.8% (w/w) glycerol, 5% (w/w) ethanol, 0.6% (w/w) nicotine and 0.6% (w/w) citric acid.

Preparation 5-85% (w/w) water, 2.0% (w/w) propylene glycol with almond flavour, 6.8% (w/w) glycerol, 5% (w/w) ethanol, 0.6% (w/w) nicotine and 0.6% (w/w) citric acid.

Preparation 6-87% (w/w) water, 2.0% (w/w) propylene glycol with almond flavour, 4.8% (w/w) glycerol, 5% (w/w) ethanol, 0.6% (w/w) nicotine and 0.6% (w/w) citric acid.

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

5 of the 7 panelists preferably had a non-flavor formulation with a water content of 85% (w/w), 1 of the 7 panelists preferably had a non-flavor formulation with a water content of 87% (w/w), and only 1 panelist preferably had a non-flavor formulation with a water content of 82% (w/w).

8 of the 9 panelists preferably had almond flavor formulations with water contents of 85% and 87% (w/w), while only 1 panelist preferably had an almond flavor formulation with a water content of 82% (w/w).

Various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. While the invention has been described in connection with certain preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in chemistry or related fields are intended to be within the scope of the following claims.

Claims

1. An aerosolizable formulation comprising

(ii) nicotine.

2. The aerosolizable formulation according to claim 1, wherein water is present in an amount of at least 90 wt.%, based on the aerosolizable formulation.

3. The aerosolizable formulation according to claim 1 or 2, wherein water is present in an amount of at least 95 wt.%, based on the aerosolizable formulation.

4. An aerosolizable formulation comprising

(ii) nicotine.

5. The aerosolizable formulation according to any one of claims 1-4, wherein water is present in an amount of at least 99 wt.%, based on the aerosolizable formulation.

6. The aerosolizable formulation according to any one of claims 1-5, wherein the nicotine is present in an amount of no more than 1 wt.%, based on the aerosolizable formulation.

7. The aerosolizable formulation according to claim 6, wherein the nicotine is present in an amount of 0.01 to 0.6 wt.% based on the aerosolizable formulation.

8. The aerosolizable formulation according to any one of claims 1-7, wherein the aerosolizable formulation further comprises an acid.

9. The aerosolizable formulation according to claim 8, 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.

10. The aerosolizable formulation according to claim 8 or 9, wherein the acid is selected from the group consisting of: citric acid, benzoic acid, levulinic acid, sorbic acid, lactic acid, and mixtures thereof.

11. The aerosolizable formulation according to any one of claims 8-10, wherein the acid is at least citric acid.

12. The aerosolizable formulation according to any one of claims 8-11, wherein the total amount of acid present in the formulation does not exceed 1 molar equivalent, based on the nicotine.

13. The aerosolizable formulation according to any one of claims 8-12, wherein the total amount of acid present in the solution is not less than 0.1 molar equivalents based on the nicotine.

14. The aerosolizable formulation according to any one of claims 1-13, further comprising one or more flavoring agents.

15. The aerosolizable formulation according to claim 14, wherein the one or more flavoring agents are selected from the group consisting of: (4-p-methoxyphenyl) -2-butanone, vanillin, gamma undecalactone, menthone, 5-propenyl guaethol, menthol, p-menthyl-8-thiol-3-one, and mixtures thereof.

16. The aerosolizable formulation according to claim 15, wherein the flavoring agent is at least menthol.

17. The aerosolizable formulation according to any one of claims 14-16, wherein the one or more flavorants are present in a total amount of no more than 2 wt.%, based on the aerosolizable formulation.

18. The aerosolizable formulation according to any one of claims 14-17, wherein the one or more flavoring agents are present in a total amount of 0.01 to 1 wt.%, based on the aerosolizable formulation.

19. The aerosolizable formulation according to any one of claims 1-18, wherein, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation is free of flavors capable of being encapsulated by the one or more cyclodextrins.

20. The aerosolizable formulation according to any one of claims 1-21, wherein, if the aerosolizable formulation comprises one or more cyclodextrins, the aerosolizable formulation is free of flavoring agents.

21. A method for forming an aerosol, the method comprising aerosolizing an aerosolizable formulation comprising:

(ii) nicotine or one or more flavoring agents.

22. A method according to claim 21, wherein the aerosolizable formulation comprises nicotine and optionally one or more flavoring agents.

23. The method according to claim 22, wherein the aerosolizable formulation is an aerosolizable formulation as defined in any one of claims 2-20.

24. A method according to claim 21, 22 or 23, wherein the aerosol is formed by a process carried out at a temperature below 50 ℃.

25. The method of any one of claims 21 to 24, wherein the aerosol is formed by applying ultrasonic energy to the aerosolizable formulation.

26. An aerosolizable formulation comprising, comprising

(a) A container; and

(b) an aerosolizable formulation comprising

(ii) nicotine.

27. The contained aerosolizable formulation according to claim 26, wherein the aerosolizable formulation is an aerosolizable formulation as defined in any one of claims 2-20.

28. The contained aerosolizable formulation according to claim 26 or 27, wherein the container is configured to interface with an electronic aerosol supply system.

29. An electronic aerosol provision system comprising:

(c) an aerosolizable formulation comprising:

(ii) nicotine or one or more flavoring agents.

30. An electronic aerosol provision system according to claim 29, wherein the aerosolizable formulation comprises nicotine and optionally one or more flavourings.

31. An electronic aerosol provision system according to claim 29 or 30, wherein the aerosolizable formulation is an aerosolizable formulation as defined in any one of claims 2 to 20.