Patent Publication Number: US-2023144701-A1

Title: Aerosolisable formulation

Description:
PRIORITY CLAIM 
     The present application is a National Phase entry of PCT Application No. PCT/GB2021/050997, filed Apr. 23, 2021, which claims priority from GB Application No. 2006008.3, filed Apr. 24, 2020, each of which is hereby fully incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates to an aerosolizable formulation, a process for forming an aerosol from the aerosolizable formulation, containers which contain the aerosolizable formulation, electronic aerosol provision systems such as electronic aerosol delivery systems (e.g. e-cigarettes) incorporating said formulation, a process for preparing an aerosolizable formulation and the use of an aerosol formed from the aerosolizable formulation. 
     BACKGROUND 
     Electronic aerosol delivery systems such as e-cigarettes generally contain a reservoir of liquid (e-liquid) which is to be turned into an aerosol, typically containing nicotine. When a user inhales on the device, a heater is activated to aerosolize or vaporize a small amount of liquid, which is inhaled by the user. Other methods of aerosolizing e-liquids are known in the art, such as by using pressurized gas or mechanical atomization to generate an aerosol. Depending on the constituents of the aerosolizable formulation that are to be provided to a user, it may be preferable to formulate the aerosolizable formulation in a certain way. For example, it may be preferable to prepare the aerosolizable formulation so as to produce an aerosol with a particular profile. It may also be preferable to prepare the aerosolizable formulation so as to ensure the aerosolizable formulation meets certain standards of quality, consistency and the like. 
     It would thus be desirable to provide an aerosolizable formulation that is formulated so as to be acceptable to a user. 
     SUMMARY 
     In one aspect there is provided an aerosolizable formulation comprising: 
     (i) one or more aerosol-forming agents; and 
     (ii) nicotine; 
     wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
     In a further embodiment there is provided a process for forming an aerosol, the process comprising aerosolizing an aerosolizable formulation comprising: 
     (i) one or more aerosol-forming agents; and 
     (ii) nicotine; 
     wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
     In a further embodiment there is provided a contained aerosolizable formulation comprising: (a) a container; and 
     (b) an aerosolizable formulation, comprising 
     (i) one or more aerosol-forming agents; and 
     (ii) nicotine; 
     wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
     In a further embodiment there is provided an electronic aerosol provision system comprising: (a) an aerosolizer for turning a formulation into an aerosol for inhalation by a user of the electronic aerosol provision system; 
     (b) a power supply for supplying power to the aerosolizer; and 
     (c) an aerosolizable formulation comprising 
     (i) one or more aerosol-forming agents; and 
     (ii) nicotine; 
     wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
     In a further embodiment there is provided a process for preparing an aerosolizable formulation comprising 
     (i) one or more aerosol-forming agents; and 
     (ii) nicotine; 
     wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine; 
     the process comprising the steps of: 
     (a) providing the nicotine; and 
     (b) contacting the one or more aerosol-forming agents with the nicotine. 
     The present invention further provides the use of (R)-nicotine for reducing irritation of an aerosol when delivered to a user&#39;s oral or nasal cavity, wherein the aerosol is formed by aerosolizing an aerosolizable formulation comprising 
     (i) one or more aerosol-forming agents; and 
     (ii) nicotine; 
     wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     As discussed herein, the present invention provides an aerosolizable formulation comprising (i) one or more aerosol-forming agents, and (ii) nicotine; wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
     Nicotine is the most abundant alkaloid in tobacco, accounting for approximately 95% of the total alkaloid content in tobacco. In addition, there are several minor chemical components in tobacco, such as nicotine-N′-oxide (e.g., nicotine-1′-N-oxide), nicotyrine (e.g., β-Nicotyrine), cotinine, nornicotyrine, 2′,3-bipyridyl, anabasine, N-methyl anatabine, N-methyl anabasine, anabasine, and anatabine. 
     The nicotine molecule contains a chirogenic centre at the C2′-position of the pyrrolidine moiety and exists as two enantiomers, (R)-nicotine and (S)-nicotine, which are the only stereochemical stable alkaloids derivable from tobacco. 
     
       
         
         
             
             
         
       
     
     (S)-nicotine is reported to be the predominant naturally occurring enantiomeric form of nicotine in tobacco, whereas (R)-nicotine is a minor form of nicotine derived from tobacco, if present at all. Typically (R)-nicotine is present in naturally derived nicotine in an amount of less than 1% of total nicotine. Studies have shown that (R)-nicotine may be present in tobacco smoke in an amount of about 2%-6% of the total nicotine content, which is likely the result of racemization during the combustion of tobacco. 
     Naturally derived (S)-nicotine is generally known to be more pharmacologically active than (R)-nicotine isomer, for example as a nicotinic acetylcholine receptor agonist. 
     We found that aerosolizable formulations comprising (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine content in the aerosolizable formulation provided an improved sensory experience and consumer satisfaction relative to aerosolizable formulations comprising predominantly (S)-nicotine. This was especially the case in aerosolizable formulations comprising high concentrations of nicotine. 
     We also found that aerosolizable formulations comprising (R)-nicotine in an amount of from about 1% to about 4.5% of the total nicotine content in the aerosolizable formulation enhanced the sensory effects associated with Flavoring and additional active agents added to the aerosolizable formulation, thereby improving the sensory experience of the user inhaling the aerosol. 
     For ease of reference, these and further aspects of the present invention are now discussed under appropriate section headings. As will be understood by the skilled person, the teachings of each section are not limited to the section in question, but may be combined with other sections as appropriate. 
     Nicotine 
     Nicotine may be provided in any suitable amount depending on the desired dosage when inhaled by the user. In one aspect nicotine is present in an amount of from about 0.1% to about 10% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 10% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 10% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 9% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 9% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 9% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 7% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 7% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 7% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 6% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 6% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 6% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 4% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 4% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 4% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 3% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 3% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 3% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 2.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 2.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 2.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 2.0% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5 to about 2.0% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 2.0% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 1.8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 1.8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 1.8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 1.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 1.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 1.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.1% to about 1.25% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 0.5% to about 1.25% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of from about 1% to about 1.25% by weight of the aerosolizable formulation. 
     In one aspect nicotine is present in an amount of no greater than about 10% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 9% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 7% based on the total weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 6% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 4% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 3% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 2.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 2.0% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 1.8% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 1.5% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 1.25% by weight of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 1.0% by weight of the aerosolizable formulation. 
     In one aspect nicotine is present in an amount of no greater than about 200 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 150 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 100 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 800 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 60 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 50 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 40 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 35 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 30 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 25 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 20 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 18 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 15 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 12 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 10 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 8 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 6 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 5 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 4 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 3 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 2 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of no greater than about 1 mg/ml of the aerosolizable formulation. 
     In one aspect nicotine is present in an amount of at least about 1 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 2 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 3 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 4 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 5 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 6 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 8 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 10 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 12 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 15 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 18 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 20 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 25 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 30 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 35 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 40 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 50 mg/ml of the aerosolizable formulation. In one aspect nicotine is present in an amount of at least about 60 mg/ml of the aerosolizable formulation. 
     As discussed herein, nicotine may comprise (S)-nicotine or (R)-nicotine in any suitable amount depending on the desired effect on the aerosolizable formulation and provided (R)-nicotine is present in an amount of from about 1.0% to about 4.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.0% to about 3.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.0% to about 3.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.5% to about 4.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.5% to about 4.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.5% to about 3.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 1.5% to about 3.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 4.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 3.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 3.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.5% to about 4.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.5% to about 4.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.5% to about 3.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 2.5% to about 3.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 3.0% to about 4.5% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 3.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine comprises (R)-nicotine in an amount of from about 3.0% to about 3.5% by weight of the total nicotine. 
     In one aspect nicotine is present in an amount of from about 0.1% to about 10% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 1.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine is present in an amount of from about 0.1% to about 10% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine is present in an amount of from about 0.1% to about 10% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 3.0% by weight of the total nicotine. In one aspect nicotine is present in an amount of from about 0.1% to about 10% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 3.0% to about 4.0% by weight of the total nicotine. 
     In one aspect nicotine is present in an amount of from about 0.5% to about 5% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 1.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine is present in an amount of from about 0.5% to about 5% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 4.0% by weight of the total nicotine. In one aspect nicotine is present in an amount of from about 0.5% to about 5% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 2.0% to about 3.0% by weight of the total nicotine. In one aspect nicotine is present in an amount of from about 0.5% to about 5% by weight of the aerosolizable formulation wherein nicotine comprises (R)-nicotine in an amount of from about 3.0% to about 4.0% by weight of the total nicotine. 
     While it is know in the art that nicotine can be extracted and purified from naturally derived sources for use in aerosolizable formulations, nicotine may also be synthetically derived in order to provide the pure enantiomeric forms of nicotine. Naturally derived nicotine and synthetically derived nicotine are distinct and distinguishable from each for a number of reasons. The term “naturally derived” refer to materials that are produced from natural or organic sources, such as tobacco plants or leaves. The term “synthetically derived” refer to materials that are manufactured using synthetic chemical processes to provide the material. In other words, the term “synthetically derived” refer to materials that are manufactured using non-natural chemical processes to provide the material. Synthetically derived nicotine is chemically identical to naturally derived nicotine and therefore shares the same physiological properties. 
     While methods for preparing synthetic nicotine have been known since the 1940s, the high cost of production has limited its use in products intended for human consumption. However, new methods are being developed to improve efficiency and reduce the costs for preparing synthetic nicotine. Methods for preparing synthetically derived nicotine are described in WO 2017/117575 A1. For example, synthetic nicotine can be prepared using the following synthetic process:
         1). React a nicotinate ester with N-vinyl-2-pyrrolidinone in the presence of a base and a solvent. Suitable bases may include metal hydrides comprising an alkali metal, such as lithium, potassium or sodium. Suitable solvents may include aromatic hydrocarbon or hydrocarbon solvents, dipolar aprotic solvents, ethers, polyethers, alcohols, toluene, xylenes, benzene and the like.   2). Combine mixture produced in step 1 with an acid, such as an aqueous hydrochloric acid solution, to form a second mixture comprising an aqueous layer.   3). Combine the separated aqueous layer with a concentrated acid, such as concentrated hydrochloric acid, to form a third mixture.   4). Combine the third mixture with a base to form a fourth mixture comprising myosamine, reducing myosamine to nornicotine using a reducing agent, such as a hydrogenation catalyst or a borohydride salt, and methylating the nornicotine to yield R, S-nicotine.       

     The above method produces a racemic mixture (50:50) of (R)- and (S)-nicotine with a purity that can exceed 99%. 
     In one aspect, the nicotine comprises a mixture of synthetically derived nicotine and naturally derived nicotine. In one aspect the nicotine comprises synthetically derived (R)-nicotine and naturally derived (S)-nicotine. In one aspect the nicotine comprises synthetically derived (R)- and (S)-nicotine. In one aspect the nicotine comprises synthetically derived (R)-nicotine and a mixture of synthetically derived (S)-nicotine and naturally derived (S)-nicotine. 
     In one aspect nicotine comprises synthetically derived (R)-nicotine in an amount of no greater than about 10% by weight of the total nicotine. In one aspect nicotine comprises synthetically derived (R)-nicotine in an amount of no greater than about 5% by weight of the total nicotine. In one aspect the nicotine comprises synthetically derived (R)-nicotine in an amount of no greater than about 3% by weight of the total nicotine. 
     In one aspect the nicotine comprises at least about 80% naturally derived (S)-nicotine, no greater than about 10% synthetically derived (S)-nicotine and no greater than about 10% synthetically derived (R)-nicotine by weight of the total nicotine. In one aspect the nicotine comprises at least about 90% naturally derived (S)-nicotine, no greater than about 5% synthetically derived (S)-nicotine and no greater than about 5% synthetically derived (R)-nicotine by weight of the total nicotine. In one aspect the nicotine comprises at least about 94% naturally derived (S)-nicotine, no greater than about 3% synthetically derived (S)-nicotine and no greater than about 3% synthetically derived (R)-nicotine by weight of the total nicotine. 
     In one aspect the nicotine comprises at least about 90% synthetically derived (S)-nicotine and no greater than about 10% synthetically derived (R)-nicotine by weight of the total nicotine. In one aspect the nicotine comprises at least about 95% synthetically derived (S)-nicotine and no greater than about 5% synthetically derived (R)-nicotine by weight of the total nicotine. In one aspect the nicotine comprises at least about 96% synthetically derived (S)-nicotine and no greater than about 4% synthetically derived (R)-nicotine by weight of the total nicotine. In one aspect the nicotine comprises at least about 97% synthetically derived (S)-nicotine and no greater than about 3% synthetically derived (R)-nicotine by weight of the total nicotine. 
     In one aspect, a racemic mixture of synthetically derived (R)- and (S)-nicotine can be combined with naturally derived nicotine, i.e. approximately 100% (S)-nicotine, in order to provide an aerosolizable formulation comprising nicotine and (R)-nicotine as defined in any one of the above embodiments. 
     Aerosol-Forming Agents 
     The aerosolizable formulation of the present invention includes one or more aerosol-forming agents. An aerosol is a suspension of particles of liquid, solid, or both, within a gas. By the term “aerosol-forming agent” is meant a compound which when included in the formulation with the nicotine, and heated to a temperature between about 100 to about 250° C., forms a suspension of nicotine in its gaseous form. In other words, the aerosol-forming agent is involved in the formation of a suspension of nicotine upon heating of the formulation. 
     The one or more aerosol-forming agents can be selected from the group consisting of glycerin (also called glycerine or glycerol), 1,3-propanediol, 1,2-propanediol (propylene glycol) and sugar alcohols (e.g. sorbitol, ethylene glycol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol). In one aspect the one or more aerosol-forming agents are selected from the group consisting of glycerol, 1,2-propanediol, 1,3-propanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, erythritol, meso-Erythritol, ethyl vanillate, ethyl laurate, diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, propylene carbonate, and combinations thereof. In one aspect the one or more aerosol-forming agents are selected from the group consisting of glycerol, 1,2-propanediol, and mixtures thereof. 
     In one aspect the aerosolizable formulation of the present invention includes two or more aerosol-forming agents. 
     In one aspect the one or more aerosol-forming agents are present in a total amount of at least about 50% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of at least about 60% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of at least about 70% by weight of the aerosolizable formulation. 
     In one aspect the one or more aerosol-forming agents are present in a total amount of from about 50% to about 90% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of from about 60% to about 90% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of from about 70% to about 90% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of from about 50% to about 80% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of from about 60% to about 80% by weight of the aerosolizable formulation. In one aspect the one or more aerosol-forming agents are present in a total amount of from about 70% to about 80% by weight of the aerosolizable formulation. 
     Other Components 
     The aerosolizable formulation of the present invention may include one or more further components. These components may be selected depending on the nature of the formulation. 
     In one aspect the aerosolizable formulation further comprises water. The water can be distinguished from the aerosol-forming agent(s) by the concentration at which it is included in the formulation. 
     In one aspect water is present in an amount of from about 0.1% to about 30% by weight of the aerosolizable formulation. In one aspect water is present in an amount of from about 5% to about 30% by weight of the aerosolizable formulation. In one aspect water is present in an amount of from about 10% to about 30% by weight of the aerosolizable formulation. In one aspect water is present in an amount of from about 15% to about 30% by weight of the aerosolizable formulation. 
     In one aspect the aerosolizable formulation is in the form of a liquid. In one aspect the aerosolizable formulation is not in the form of a gel. 
     In one aspect the formulation further comprises an active agent in addition to nicotine. By “active agent” it is meant an agent that imparts a physiologically active material, i.e. a material intended to achieve or enhance a physiological response. The additional active agent may for example be selected from nutraceuticals, nootropics, psychoactives. The additional active agent may be naturally occurring or synthetically obtained. The additional active agent may comprise for example caffeine, taurine, theine, vitamins such as B6 or B12 or C, melatonin, cannabinoids, or constituents, derivatives, or combinations thereof. The additional active agent may comprise one or more constituents, derivatives or extracts of cannabis or another botanical. 
     In one aspect, the additional active agent comprises caffeine, melatonin or vitamin B12. As discussed herein, the additional active agent may comprise or be derived from one or more botanicals or constituents, derivatives or extracts thereof. As used herein, the term “botanical” includes any material derived from plants including, but not limited to, extracts, leaves, bark, fibers, stems, roots, seeds, flowers, fruits, pollen, husk, shells or the like. Alternatively, the material may comprise an active compound naturally existing in a botanical, obtained synthetically. The material may be in the form of liquid, gas, solid, powder, dust, crushed particles, granules, pellets, shreds, strips, sheets, or the like. Example botanicals are eucalyptus, star anise, hemp, cocoa, cannabis, fennel, lemongrass, peppermint, spearmint, rooibos, chamomile, flax, ginger,  Ginkgo biloba , hazel, hibiscus, laurel, licorice (liquorice), matcha, mate, orange skin, papaya, rose, sage, tea such as green tea or black tea, thyme, clove, cinnamon, coffee, aniseed (anise), basil, bay leaves, cardamom, coriander, cumin, nutmeg, oregano, paprika, rosemary, saffron, lavender, lemon peel, mint, juniper, elderflower, vanilla, wintergreen, beefsteak plant, curcuma, turmeric, sandalwood, cilantro, bergamot, orange blossom, myrtle, cassis, valerian, pimento, mace, damien, marjoram, olive, lemon balm, lemon basil, chive, carvi, verbena, tarragon, geranium, mulberry, ginseng, theanine, theacrine, maca, ashwagandha, damiana, guarana, chlorophyll, baobab or any combination thereof. The mint may be chosen from the following mint varieties:  Mentha  Arventis,  Mentha  c.v.,  Mentha niliaca, Mentha piperita, Mentha piperita citrata  c.v.,  Mentha piperita  c.v,  Mentha spicata crispa, Mentha cardifolia, Mentha longifolia, Mentha  suaveolens variegata,  Mentha  pulegium,  Mentha spicata  c.v. and  Mentha suaveolens    
     In one aspect, the additional active agent comprises or derived from one or more botanicals or constituents, derivatives or extracts thereof and the botanical is selected from eucalyptus, star anise, cocoa and hemp. In one aspect, the additional active agent comprises or is derived from one or more botanicals or constituents, derivatives or extracts thereof and the botanical is selected from rooibos and fennel. 
     Flavoring Agents 
     The aerosolizable formulation of the present invention may further comprise one or more a flavoring agents. The terms “flavoring agent”, “flavor” or “flavorant” refer to materials which, where local regulations permit, may be used to create a desired taste, aroma or other somatosensorial sensation in a product for adult consumers. They may include naturally occurring flavor materials, botanicals, extracts of botanicals, synthetically obtained materials, or combinations thereof (e.g., tobacco, cannabis, licorice (liquorice), hydrangea, eugenol, Japanese white bark magnolia leaf, chamomile, fenugreek, clove, maple, matcha, menthol, Japanese mint, aniseed (anise), cinnamon, turmeric, Indian spices, Asian spices, herb, wintergreen, cherry, berry, red berry, cranberry, peach, apple, orange, mango, clementine, lemon, lime, tropical fruit, papaya, rhubarb, grape, durian, dragon fruit, cucumber, blueberry, mulberry, citrus fruits, Drambuie, bourbon, scotch, whiskey, gin, tequila, rum, spearmint, peppermint, lavender, aloe vera, cardamom, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, khat, naswar, betel, shisha, pine, honey essence, rose oil, vanilla, lemon oil, orange oil, orange blossom, cherry blossom, cassia, caraway, cognac, jasmine, ylang-ylang, sage, fennel, wasabi, piment, ginger, coriander, coffee, hemp, a mint oil from any species of the genus  Mentha , eucalyptus, star anise, cocoa, lemongrass, rooibos, flax,  Ginkgo biloba , hazel, hibiscus, laurel, mate, orange skin, rose, tea such as green tea or black tea, thyme, juniper, elderflower, basil, bay leaves, cumin, oregano, paprika, rosemary, saffron, lemon peel, mint, beefsteak plant, curcuma, cilantro, myrtle, cassis, valerian, pimento, mace, damien, marjoram, olive, lemon balm, lemon basil, chive, carvi, verbena, tarragon, limonene, thymol, camphene), flavor enhancers, bitterness receptor site blockers, sensorial receptor site activators or stimulators, sugars and/or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharine, 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 blends thereof. They may be in any suitable form, for example, liquid such as an oil, solid such as a powder, or gas. 
     In one aspect, the flavor comprises menthol, spearmint and/or peppermint. In one aspect, the flavor comprises flavor components of cucumber, blueberry, citrus fruits and/or redberry. In one aspect, the flavor comprises eugenol. In one aspect, the flavor comprises flavor components extracted from tobacco. In one aspect, the flavor comprises flavor components extracted from cannabis. 
     In one aspect, the flavor may comprise a sensate, which is intended to achieve a somatosensorial sensation which are usually chemically induced and perceived by the stimulation of the fifth cranial nerve (trigeminal nerve), in addition to or in place of aroma or taste nerves, and these may include agents providing heating, cooling, tingling, numbing effect. A suitable heat effect agent may be, but is not limited to, vanillyl ethyl ether and a suitable cooling agent may be, but not limited to eucolyptol, WS-3. 
     The flavoring agent is present in any amount to deliver the desired flavor to the aerosolizable formulation. The amount of the flavoring agent is defined with respect to the total weight of the aerosolizable formulation. In one aspect the flavoring agent is food-grade. As will be understood by the skilled person, the term “food-grade” refers to materials which are non-toxic and safe for human consumption. 
     In one aspect the flavoring agent is present in an amount of no greater than about 10 wt. % based on the aerosolizable formulation. In one aspect the flavoring agent is present in an amount of no greater than about 5 wt. %. In one aspect the flavoring agent is present in an amount of no greater than about 2 wt. %. In one aspect the flavoring agent is present in an amount of no greater than about 1.0 wt. %. In one aspect the flavoring agent is present in an amount of no greater than about 0.75 wt. %. In one aspect the flavoring agent is present in an amount of no greater than about 0.5 wt. %. 
     In one aspect the flavoring agent is present in an amount of from about 0.01 to about 10 wt. % based on the aerosolizable formulation. In one aspect the flavoring agent is present in an amount of from about 0.01 to about 5 wt. % based on the aerosolizable formulation. In one aspect the flavoring agent is present in an amount of from about 0.01 to about 2 wt. % based on the aerosolizable formulation. In one aspect the flavoring agent is present in an amount of from about 0.01 to about 1.0 wt. % based on the aerosolizable formulation. In one aspect the flavoring agent is present in an amount of from about 0.01 to about 0.75 wt. % based on the aerosolizable formulation. In one aspect the flavoring agent is present in an amount of from about 0.01 to about 0.5 wt. % based on the aerosolizable formulation. 
     It will be understood by the skilled person that the flavoring agent may be a multi-component flavoring agent or a single component flavoring agent. When the formulation includes more than one such flavorants, each can be included at the above defined amounts. v 
     Processes 
     As discussed herein, the present invention provides a process for forming an aerosol, the process comprising aerosolizing an aerosolizable formulation as defined herein. In one aspect, the aerosol is formed by a process performed at a temperature of from about 100° C. to about 250° C. 
     In another aspect is a process for forming an aerosol, the process comprising aerosolizingaerosolizing an aerosolizable formulation as defined herein by a process performed using a pressurizedpressurized gas or mechanical atomizationatomization. 
     Also discussed herein, the present invention provides a process for preparing an aerosolizable formulation comprising (i) one or more aerosol-forming agents; and (ii) nicotine; wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine; the process comprising the steps of (a) providing the nicotine; and (b) contacting the one or more aerosol-forming agents with the nicotine. In one aspect of this process, step (a) comprises combining a racemic mixture of synthetic nicotine with naturally derived nicotine such that the amount of (R)-nicotine is from about 1% to about 4.5% by weight of the total nicotine. In one aspect of this process, step (a) comprises combining a racemic mixture of synthetic nicotine with naturally derived nicotine such that the amount of (R)-nicotine is in an amount as defined in any one of the embodiments defined herein. 
     Further Aspects 
     The aerosolizable formulation may be contained or delivered by any means. In one aspect the present invention provides a contained aerosolizable formulation comprising (a) a container; and (b) an aerosolizable formulation as defined herein. 
     The container may be any suitable container, for example to allow for the storage or delivery of the solution. In one aspect the container is configured for engagement with an electronic aerosol provision system. The container may be a bottle. The container may be configured to become in communication with an electronic aerosol provision system, such as in fluid communication, so that solution may be delivered to the electronic aerosol provision system. As described above, the present disclosure relates to container which may be used in an electronic aerosol provision system, such as an e-cigarette. Throughout the following description the term “e-cigarette” is used; however, this term may be used interchangeably with electronic aerosol provision system. 
     As discussed herein, the container of the present invention is typically provided for the delivery of aerosolizable formulation to or within an e-cigarette. The aerosolizable formulation may be held within an e-cigarette or may be sold as a separate container for subsequent use with or in an e-cigarette. It is well known in the art that aerosolizable formulations that are suitable for use in e-cigarettes are often referred to as “e-liquids”. In one aspect the aerosolizable formulation of the present invention is an e-liquid. As understood by one skilled in the art, e-cigarettes may contain a unit known as a detachable cartomizercartomizer which typically comprises a reservoir of aerosolizable formulation, a wick material and a device for aerosolizing the aerosolizable formulation. In some e-cigarettes, the cartomizer is part of a single-piece device and is not detachable. In one aspect the container is a cartomizer or is part of a cartomizercartomizer. In one aspect the container is not a cartomizer or part of a cartomizer and is a container, such as a tank, which may be used to deliver aerosolizable formulation to or within an e-cigarette. 
     In one aspect the container is part of an e-cigarette. Therefore in a further aspect the present invention provides an electronic aerosol provision system comprising: (a) an aerosolizer for aerosolizing formulation for inhalation by a user of the electronic aerosol provision system; (b) a power supply for supplying power to the aerosolizer (c) an aerosolizable formulation as defined herein. In one aspect the power supply comprises a cell or battery for supplying power to the aerosolizer. 
     In addition to the aerosolizable formulation of the present invention and to systems such as containers and electronic aerosol provision systems containing the same, the present invention provides use of (R)-nicotine for reducing irritation of an aerosol when delivered to a user&#39;s oral or nasal cavity, wherein the aerosol is formed by aerosolizing an aerosolizable formulation comprising (i) one or more aerosol-forming agents; and (ii) nicotine; wherein the nicotine comprises (R)-nicotine in an amount of from about 1% to about 4.5% by weight of the total nicotine. 
     EXAMPLES 
     Example 1 
     The satisfaction performance of aerosolizable formulations comprising naturally derived or synthetically derived nicotine was evaluated. 
     A sequential monadic study was carried out involving 114 participants, who were either users of factory-made cigarettes (FMC) or dualists (consumers of both FMC and e-cigarettes). The study group consisted of 50% males and 50% females. 
     Each participant consumed 2 separate aerosolizable formulations comprising (i) 18 mg/ml of naturally derived nicotine and (ii) 18 mg/ml of synthetically derived nicotine. Both formulations consisted of 100% (S)-nicotine after initial product testing and were Flavored with “rich tobacco” Flavor. The participants used an ePen3 aerosol delivery device (produced by British American Tobacco) to consume each formulation. 
     This study was used to assess the satisfaction performance of aerosolizable formulations comprising either naturally derived nicotine or synthetically derived nicotine. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                 Sample A 
                 Sample B 
               
               
                   
                 Naturally Derived 
                 Synthetically Derived 
               
               
                   
                 Nicotine 
                 Nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 Flavor liking (Mean) 
                 2.7 
                 2.8 
               
               
                 Mild Taste (Mean) 
                 2.5 
                 2.4 
               
               
                 Smooth Taste (Mean) 
                 2.7 
                 2.6 
               
               
                 Not Bitter Taste (Mean) 
                 3.0 
                 2.8 
               
               
                 Mild Pepper Taste (Mean) 
                 3.2 
                 3.2 
               
               
                   
               
               
                 Significance test at 90% confidence interval 
               
               
                 Flavor Liking was measured on a scale of 1 to 5: 1 representing a “dislike of Flavor” and 5 representing a “liking of the Flavor”. 
               
               
                 Mild Taste was measured on a scale of 1 to 5: 1 representing “strong taste” and 5 representing “mild taste”. 
               
               
                 Smooth Taste was measured on a scale of 1 to 5: 1 representing a “harsh taste” and 5 representing a “smooth taste”. 
               
               
                 Not Bitter Taste was measured on a scale of 1 to 5: 1 representing “bitter” and 5 representing “not bitter”. 
               
               
                 Mild Pepper Taste was measured on a scale of 1 to 5: 1 representing “strong taste” and 5 representing “mild peppery taste”. 
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Sample A 
                 Sample B 
               
               
                   
                 Naturally Derived 
                 Synthetically Derived 
               
               
                   
                 Nicotine 
                 Nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 Flavor Liking (Mean) 
                 2.7 
                 2.9 
               
               
                 Flavor Pleasantness (Mean) 
                 2.7 
                 2.7 
               
               
                 Taste Intensity/Amount % JR 
                 46% 
                 46% 
               
               
                 Aroma During Usage % JR 
                 62% 
                 67% 
               
               
                 End of Usage After Taste % 
                 48% 
                 48% 
               
               
                 JR 
               
               
                   
               
               
                 Significance test at 90% confidence interval 
               
               
                 % JR is used to determine intensity of specific sensory attributes relative to one&#39;s hypothetical satisfactory level, which can affect the acceptance of the overall product. Acceptance tests are used to identify the liking of a product and individual product attributes. 
               
               
                 % JR is also frequently referred to as a “Just Right” (JR) scale or “Just about Right” scale (JAR). 
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                 Sample A 
                 Sample B 
               
               
                   
                 Naturally Derived 
                 Synthetically Derived 
               
               
                   
                 Nicotine 
                 Nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 Satisfaction (Mean) 
                 2.7 
                 2.9 
               
               
                 Overall rating - T3B 
                 46% 
                 50% 
               
               
                   
               
               
                 Significance test at 90% confidence interval 
               
               
                 Satisfaction of the participant was measured on a scale of 1 to 5: 1 representing “unsatisfied” and 5 representing “satisfied”. 
               
               
                 The overall rating by the participant was measured on a scale of 1 to 5: 1 representing “poor” and 5 representing “excellent”. 
               
               
                 T3B is defined as a “Top 3 Box” score, associated with the Box Score analytical method. This analytical method is used as a way of summarizing the positive responses from a Likert scale (i.e. a psychometric scale) survey question by combining the highest 3 responses to create a rating. 
               
            
           
         
       
     
     No significant difference was observed between the use of synthetically derived nicotine and naturally derived nicotine in terms of taste, Flavor or pleasantness. Sample A and Sample B are therefore comparable. 
     Example 2 
     The satisfaction performance of aerosolizable formulation comprising different racemic ratios of (S)- and (R)-nicotine was evaluated. 
     A sequential monadic study was carried out involving 114 participants, who were either users of factory-made cigarettes (FMC) or dualists (consumers of both FMC and e-cigarettes). The study group consisted of 50% males and 50% females. 
     Each participant consumed 4 aerosolizable formulations comprising of 18 mg/ml of isomeric nicotine and Flavored with “rich tobacco” Flavor. Said formulations consisted of naturally derived (S)-nicotine and synthetically derived (R)-nicotine in racemic ratios as defined in Tables 4-8. The participants used an ePen3 aerosol delivery device (produced by British American Tobacco) to consume each formulation. 
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 4 
               
               
                   
                   
               
               
                   
                   
                 Sample C 
                 Sample D 
                 Sample E 
               
               
                   
                   
                 97% (S)- 
                 95% (S)- 
                 90% (S)- 
               
               
                   
                 Sample A 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                 100% (S)- 
                 3% (R)- 
                 5% (R)- 
                 10% (R)- 
               
               
                   
                 nicotine 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Flavor Liking 
                 2.7 
                 2.9      
                 2.8      
                 2.9 
               
               
                 (Mean) 
               
               
                 Mild Taste 
                 2.5 
                     2.9 A * 
                  3.1 AE * 
                 2.7 
               
               
                 (Mean) 
               
               
                 Smooth Taste 
                 2.7 
                 3.0 a  †   
                 3.0 a  †   
                 2.8 
               
               
                 (Mean) 
               
               
                 Not Bitter 
                 3.0 
                 3.3 e  †   
                 3.2      
                 3 
               
               
                 Taste (Mean) 
               
               
                 Mild Pepper 
                 3.2 
                       3.6 ADE * 
                 3.4 e  †   
                 3.1 
               
               
                 Taste (Mean) 
               
               
                   
               
               
                   †  Significance test at 90% confidence interval 
               
               
                 * Significance test at 95% confidence interval 
               
               
                 Flavor Liking was measured on a scale of 1 to 5: 1 representing a “dislike of Flavor” and 5 representing a “liking of the Flavor”. 
               
               
                 Mild Taste was measured on a scale of 1 to 5: 1 representing “strong taste” and 5 representing “mild taste”. 
               
               
                 Smooth Taste was measured on a scale of 1 to 5: 1 representing a “harsh taste” and 5 representing a “smooth taste”. 
               
               
                 Not Bitter Taste was measured on a scale of 1 to 5: 1 representing “bitter” and 5 representing “not bitter”. 
               
               
                 Mild Pepper Taste was measured on a scale of 1 to 5: 1 representing “strong taste” and 5 representing “mild peppery taste”. 
               
               
                 Sample C was less bitter, less peppery and had a milder taste relative to Sample A, Sample D and Sample E, which provided for a better overall experience. 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 5 
               
               
                   
                   
               
               
                   
                   
                 Sample C 
                 Sample D 
                 Sample E 
               
               
                   
                   
                 97% (S)- 
                 95% (S)- 
                 90% (S)- 
               
               
                   
                 Sample A 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                 100% (S)- 
                 3% (R)- 
                 5% (R)- 
                 10% (R)- 
               
               
                   
                 nicotine 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Likes - Smooth/Not 
                 7% 
                 25% A * 
                 18% A * 
                   17% A * 
               
               
                 Harsh 
               
               
                 Likes - Not Too 
                 1% 
                     15% AE * 
                  8% A * 
                 3% 
               
               
                 Strong 
               
               
                 Dislike - Don&#39;t Get 
                 3% 
                 11% A*  
                 10% A * 
                 5% 
               
               
                 a Hit of Nicotine 
               
               
                 Dislike - 
                 16%  
                 11%    
                 8%   
                   18% D * 
               
               
                 Unpleasant 
               
               
                 Aftertaste 
               
               
                 Dislike - Artificial 
                 4% 
                 2%   
                 4%   
                 9% 
               
               
                 Flavor 
               
               
                   
               
               
                 * Significance test at 95% confidence interval 
               
               
                 Sample C was less bitter, less peppery and had a milder taste relative to Sample A, Sample D and Sample E, which provided for a better overall experience. 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 6 
               
               
                   
                   
               
               
                   
                   
                 Sample C 
                 Sample D 
                 Sample E 
               
               
                   
                   
                 97% (S)- 
                 95% (S)- 
                 90% (S)- 
               
               
                   
                 Sample A 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                 100% (S)- 
                 3% (R)- 
                 5% (R)- 
                 10% (R)- 
               
               
                   
                 nicotine 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Flavor Liking 
                 2.7 
                 2.9 
                 2.8 
                 2.9 
               
               
                 (Mean) 
               
               
                 Flavor Pleasantness 
                 2.7 
                 2.9 
                 3.1 
                 2.8 
               
               
                 (Mean) 
               
               
                 Taste Intensity/ 
                 46% 
                     63% a  †   
                 57% 
                 54% 
               
               
                 Amount % JR 
               
               
                 Aroma During 
                 62% 
                 66% 
                 70% 
                 70% 
               
               
                 Usage % JR 
               
               
                 End of Usage After 
                 48% 
                 59% 
                    61% A * 
                 53% 
               
               
                 Taste % JR 
               
               
                   
               
               
                   †  Significance test at 90% confidence interval 
               
               
                 * Significance test at 95% confidence interval 
               
               
                 Flavor Liking was measured on a scale of 1 to 5: 1 representing a “dislike of Flavor” and 5 representing a “liking of the Flavor”. 
               
               
                 Flavor Pleasantness was measured on a scale of 1 to 5: 1 representing “unpleasant” and 5 representing “pleasant”. 
               
               
                 % JR is used to determine intensity of specific sensory attributes relative to one&#39;s hypothetical satisfactory level, which can affect the acceptance of the overall product. Acceptance tests are used to identify the liking of a product and individual product attributes. 
               
               
                 % JR is also frequently referred to as a “Just Right” (JR) scale or “Just about Right” scale (JAR). 
               
               
                 Sample C provided optimal taste intensity and end of usage aftertaste. Flavor liking and pleasantness were comparable to Sample A, i.e. formulations consisting of naturally derived (S)-nicotine and similar to the taste of natural tobacco. 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 7 
               
               
                   
                   
               
               
                   
                   
                 Sample C 
                 Sample D 
                 Sample E 
               
               
                   
                   
                 97% (S)- 
                 95% (S)- 
                 90% (S)- 
               
               
                   
                 Sample A 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                 100% (S)- 
                 3% (R)- 
                 5% (R)- 
                 10% (R)- 
               
               
                   
                 nicotine 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Irritation 
                 2.3 
                 2.1 
                 2.3 
                 2.4 c  †   
               
               
                 Level 
               
               
                 (Mean) 
               
               
                 Coughed at 
                 35% 
                 28% 
                 33% 
                       48% ACD * 
               
               
                 First Puff 
               
               
                 (% Yes) 
               
               
                 Throat 
                 49% 
                 56% 
                 56% 
                 54% 
               
               
                 Kick - 
               
               
                 % JR 
               
               
                 Vapor 
                 70% 
                 71% 
                 76% 
                 74% 
               
               
                 Inhaled 
               
               
                 % JR 
               
               
                 Chest Impact 
                 68% 
                 66% 
                 66% 
                 70% 
               
               
                 % JR 
               
               
                 Smoothness 
                 50% 
                     61% a  †   
                 58% 
                 52% 
               
               
                 % JR 
               
               
                   
               
               
                   †  Significance test at 90% confidence interval 
               
               
                 * Significance test at 95% confidence interval 
               
               
                 Irritation Level was measured on a scale of 1 to 5: 1 representing a “low irritation” and 5 representing a “high irritation”. 
               
               
                 Sample C provided optimal smoothness when consumed. 
               
               
                 Sample D caused higher levels of coughing and irritation in study participants. 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 8 
               
               
                   
                   
               
               
                   
                   
                 Sample C 
                 Sample D 
                 Sample E 
               
               
                   
                   
                 97% (S)- 
                 95% (S)- 
                 90% (S)- 
               
               
                   
                 Sample A 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                 100% (S)- 
                 3% (R)- 
                 5% (R)- 
                 10% (R)- 
               
               
                   
                 nicotine 
                 nicotine 
                 nicotine 
                 nicotine 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Satisfaction (Mean) 
                 2.7 
                 3.0 A * 
                 2.9 
                 2.9 
               
               
                 Overall rating - 
                 46% 
                 56% 
                 52% 
                 48% 
               
               
                 T3B 
               
               
                   
               
               
                 * Significance test at 95% confidence interval 
               
               
                 Satisfaction of the participant was measured on a scale of 1 to 5: 1 representing “unsatisfied” and 5 representing “satisfied”. 
               
               
                 The overall rating by the participant was measured on a scale of 1 to 5: 1 representing “poor” and 5 representing “excellent”. 
               
               
                 T3B is defined as a “Top 3 Box” score, associated with the Box Score analytical method. This analytical method is used as a way of summarizing the positive responses from a Likert scale (i.e. a psychometric scale) survey question by combining the highest 3 responses to create a rating. 
               
            
           
         
       
     
     The satisfaction of participants was significantly higher for Sample C than for formulations consisting of (S)-nicotine, i.e. Sample A. 
     Sample D showed a directional advantage relative to Sample A and Sample E, while Samples A and E were considered comparable in terms of satisfaction and overall rating. Various modifications and variations of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the 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.