Consumables for aerosolisable or vaporisable formulations comprising acetals, the acetals being a reaction product of a c3 to CI8 keto acid and a polyhydric alcohol, or a c2 to c18 carboxy-aldehyde and a polyhydric alcohol.

Abstract

There is provided a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to C18 keto acid and a polyhydric alcohol, or a C2 to C18 carboxy-aldehyde and a polyhydric alcohol. Also provided is a substance delivery system comprising the consumable. The present disclosure also relates to the use of said consumable, containers comprising the formulation, and processes of generating an aerosol or vapour using the formulation.

Description

CONSUMABLEFIELD OF THE INVENTION

[0001] The present disclosure relates to a consumable for an aerosolisable or vaporisable formulation, in particular an aerosolisable formulation suitable for use with an electronic aerosol provision system such as an e-cigarette. Also provided is a substance delivery system comprising the consumable. The present disclosure also relates to the use of said consumable, containers comprising the formulation, and processes of generating an aerosol or vapour using the formulation.BACKGROUND

[0002] Devices have been developed which allow a user to replicate parts of the smoking experience without having to use conventional cigarettes. In particular, devices such as e-cigarettes have been developed which allow a user to generate an artificial aerosol which can then be inhaled to replicate the smoking experience. The aerosol is typically produced by vaporising a liquid which comprises an aerosol forming component such as glycerol. The vaporisation occurs via a heater (or other atomization means) which is powered by a power source such as a battery.

[0003] Other devices are also available which seek to replicate the smoking experience without having to use conventional cigarettes. These devices may be referred to as tobacco heating devices, since they generally have the capacity to heat tobacco but not combust it.

[0004] Collectively, e-cigarettes and tobacco heating devices may be referred to as aerosol delivery devices or aerosol provision systems. However, one potential drawback with such devices or systems, in particular with e-cigarettes, is that they may fail to completely replicate the sensorial experience normally associated with smoking a conventional cigarette, which users of conventional cigarettes may find less desirable.

[0005] Some consumers may prefer an e-cigarette that generates an aerosol that closely 'mimics' smoke inhaled from a tobacco product, such as a cigarette. Aerosols from e-cigarettes and smoke from tobacco products such as cigarettes provides to the user a complex chain of flavour in the mouth, nicotine absorption in the mouth and throat, followed by nicotine absorption in the lungs. These various aspects are described by users in terms of flavour, intensity / quality, impact, irritation / smoothness and nicotine reward. Providing means to optimise these factors and affect the overall vaping experience is therefore desirable to e-cigarette manufacturers. It was surprisingly found that the use of acetals and hemiacetals candesirably impact the overall vaping experience.

[0006] Containers, packages or cartridges containing consumables for an aerosolisable or vaporisable formulation or other aerosol-free delivery system typically comprise a solvent. The solvent may be a polyhydric alcohol, such as glycerol. The containers, packages or cartridges are often stored for significant periods from the time of manufacture until consumption by the user. This period includes the time of distribution, stocking by a retailer and storage by the end user before use. During this storage period, loss of active components, such as nicotine, may occur. A further advantage of the present invention is to employ acetals and hemiacetals to prevent loss of active components.SUMMARY OF THE INVENTION

[0007] In accordance with some embodiments described herein, there is provided a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to C keto acid and a polyhydric alcohol, or a C2 to C carboxy-aldehyde and a polyhydric alcohol.

[0008] In one aspect there is provided a formulation for a substance delivery system, wherein the formulation comprises polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (II):wherein m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;R3 is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb; orR3and R4are independently selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb;each of R5and R6are independently selected from H, C1.6 alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rb is selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R3, R4, Rs, Re, Rb and / or Rcis substituted by C(O)OH.

[0009] In one aspect there is provided an aerosol comprising one or more acetal, wherein the acetal is a reaction product of a C3 to C keto acid and polyhydric alcohol, or a C2 to C carboxy-aldehyde and polyhydric alcohol, preferably wherein the C3 to C keto acid, the C2 to Cis carboxy-aldehyde and polyhydric alcohol

[0010] In one aspect there is provided a vaporisable formulation for a vapour provision system comprising a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to Cis keto acid and a polyhydric alcohol, or a C2 to C carboxy-aldehyde and a polyhydric alcohol.

[0011] In one aspect there is provided a container or package containing a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to C keto acid and a polyhydric alcohol, or a C2 to C carboxy-aldehyde and a polyhydric alcohol.

[0012] In one aspect there is provided a substance delivery system comprising a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to C keto acid and a polyhydric alcohol, or a C2 to C carboxy-aldehyde and a polyhydric alcohol.

[0013] In one aspect there is provided a method of preparing a formulation for a substance delivery system, the method comprising:(a) reacting a C3 to C keto acid or a C2 to C carboxy-aldehyde with polyhydric alcohol to form a product comprising one or more acetals, and(b) preparing the formulation with the reaction product comprising one or more acetals formed by step (a).

[0014] In one aspect there is provided a formulation for a substance delivery system, wherein the formulation comprises polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (Ila):wherein m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;R3 is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb; orR3 and R4 are independently selected from H, OH, CH(O), C(O)OH, C(O)Rb, or C(O)ORb, Ci- 6 alkyl, Ci-6 alkenyl or C3-14 aryl, wherein the alkyl, alkenyl and / or aryl moieties are optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb; each of R5 and Re are independently selected from H, OH, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb; each Rb is selected from H, OH, th theCi-6 alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) C(O)OH or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from H, OH, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R3, R4, Rs, Re, Rb and / or Rcis substituted by C(O)OH.

[0015] In one aspect there is provided an aerosolisable or vaporisable formulation obtained from the abovementioned method.

[0016] In one aspect there is provided a cartridge for an aerosol provision system, the cartridge comprising a formulation for a substance delivery system, wherein the formulation comprises polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (II), as defined herein.

[0017] In one aspect there is provided a method of preparing the abovementioned cartridge, wherein the method comprises placing a aerosolisable formulation comprising a polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (II), into a reservoir comprised within a housing of the cartridge

[0018] In one aspect there is provided a cartridge for an aerosol provision system, the cartridge comprising a formulation for a substance delivery system, wherein the formulationcomprises polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (Ila), as defined herein.

[0019] In one aspect there is provided a method of preparing the abovementioned cartridge, wherein the method comprises placing a aerosolisable formulation comprising a polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (Ila), into a reservoir comprised within a housing of the cartridgeBRIEF DESCRIPTION OF THE DRAWINGS

[0020] Having thus described aspects of the disclosure in the foregoing general terms, reference will now be made to the accompanying figures. The figures are exemplary only and should not be construed as limiting the disclosure.

[0021] Figure 1 is a schematic representation of an example aerosol provision system.

[0022] Figure 2 is a mass spectra of a consumable prepared using a pre-formulated levulinic acid / glycerol product.

[0023] Figure 3 is a mass spectra of a consumable prepared using a pre-formulated levulinic acid / glycerol / propylene glycol product.

[0024] Figure 4 is a mass spectra of a consumable prepared using a pre-formulated levulinic acid / glycerol product at point of formulation (i.e. T=0hr).

[0025] Figure 5 is a mass spectra of a consumable prepared using a pre-formulated levulinic acid / glycerol product after storage (i.e. T=18hr).

[0026] Figure 6 is a mass spectra of consumable prepared using a single step manufacturing process.

[0027] Figure 7 is a chromatogram of a consumable prepared using a pre-formulated 4-formylbenzoic acid / glycerol product at point of formulation (i.e. T=0hr).

[0028] Figure 8 is a chromatogram of a consumable prepared using a pre-formulated 4-formylbenzoic acid / glycerol product after storage (i.e. T=2hr).

[0029] Figure 9 is a chromatogram of a consumable prepared using a pre-formulated 4-formylbenzoic acid / glycerol product after storage (i.e. T=20hr).

[0030] Figure 10 is a chromatogram of a consumable prepared using a pre-formulated glyoxylic acid / glycerol product after storage (i.e. T=2hr).

[0031] Figure 11 is a chromatogram of a consumable prepared using a pre-formulated pyruvic acid I glycerol product at point of formulation (i.e. T=0hr).

[0032] Figure 12 is a chromatogram of a consumable prepared using a pre-formulated pyruvic acid I glycerol product after storage (i.e. T=20hr).

[0033] Figure 13 is a chromatogram of a consumable prepared using a pre-formulated pyruvic acid 12-methyl 1 ,3 propanediol product at point of formulation (i.e. T=0hr).

[0034] Figure 14 is a chromatogram of a consumable prepared using a pre-formulated pyruvic acid 12-methyl 1,3 propanediol product after storage (i.e. T=20hr).

[0035] Figure 15 is a chromatogram of a consumable prepared using a pre-formulated a-ketoglutaric acid 12-methyl 1 ,3 propanediol product at point of formulation (i.e. T=0hr).

[0036] Figure 16 is a chromatogram of a consumable prepared using a pre-formulated a-ketoglutaric acid 12-methyl 1,3 propanediol product after storage (i.e. T=20hr).DETAILED DESCRIPTION

[0037] It is to be understood that this invention is not limited to the particular configurations, process steps, and materials disclosed herein as such configurations, process steps, and materials may vary somewhat. It is also to be understood that the terminology employed herein is used for the purpose of describing particular embodiments only and is not intended to be limiting since the scope of the present invention will be limited only by the appended claims and equivalents thereof.

[0038] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Reference to "dry % by weight" or "dry weight basis" refers to weighton the basis of dry ingredients (i.e., all ingredients except water or carrier). Reference to "wet weight" refers to the weight of the formulation or composition including water or carrier. Unless otherwise indicated, reference to "% by weight" (or “% by weight”) of formulation or composition reflects the total wet weight of the formulation or composition (i.e., including water / carrier).

[0039] Where used herein, "and / or" is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, "X and / or Y" is to betaken as specific disclosure of each of (i) X, (ii) Y, and (iii) X and Y, just as if each is set out individually herein.

[0040] In this specification, unless otherwise stated, the term "about" modifying the quantity of an ingredient in the formulation of the invention or employed in the methods of the invention refers to variation in the numerical quantity that can occur, for example, through typical measuring and liquid handling procedures used for making concentrates or use solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients employed to make the formulation, or to carry out the methods; and the like. The term “about” also encompasses amounts that differ due to different equilibrium conditions for a formulation or composition resulting from a particular initial mixture. Whether or not modified by the term "about", the claims include equivalents to the quantities.

[0041] As noted in the background above, aerosol provision devices or systems typically allow a user to replicate parts of the smoking experience without having to use conventional combustible tobacco products such as cigarettes. Specifically, aerosol provision systems are intended to produce an aerosol which can be inhaled by the user to replicate the smoking experience. The aerosol produced by such systems does not, however, completely replicate the sensorial experience typically associated with smoking tobacco. Also provided are vapour provision devices or systems aimed at replicating parts of the smoking experience, such devices or systems are intended to produce a vapour which can be inhaled by a user but similarly, the vapour produced by such systems does not completely replicate the sensorial experience typically associated with smoking tobacco.

[0042] The meaning of “aerosol” and “vapour” and terms associated therewith (e.g. aerosolisable or vaporisable) would be readily understood by the person skilled in the art.

[0043] As will be understood by one skilled in the art, an “aerosolisable formulation” is a formulation that is capable of generating aerosol, for example when heated, irradiated or energized in any other way. An “aerosolisable formulation”, namely an aerosol-generating formulation, may, for example, be in the form of a solid, liquid or semi-solid (such as a gel) which may or may not contain an active substance and / or flavourant(s). In preferred embodiments, the aerosolisable formulation is in the form of a liquid or gel.

[0044] As will be understood by one skilled in the art, a “vaporisable formulation” is a formulation that is capable of generating vapour, for example when heated, irradiated or vaporised in any other way including an evaporative process that does not involve theapplication of heat or irradiation. A “vaporisable formulation”, namely a vapour-generating formulation, may, for example, be in the form of a solid, liquid, or semi-solid (such as a gel) which may or may not contain an active substance and / or flavourant(s). The “sensorial gap” between the use of known aerosolisable / vaporisable formulations and smoking combustible tobacco products (e.g. cigarettes) includes the flavour experienced by the consumer. Flavour is the combination of taste, aroma, and chemical sensations, and it has been surprisingly found that the combination of compounds in the present claims is able to modify the flavour of an aerosolisable / vaporisable formulation and thereby reduce this “sensorial gap”. It has also been found that the combination of compounds in the present claims is able to modify the flavour of a pouched oral product, i.e. package, comprising a saliva permeable pouch.

[0045] One skilled in the art would also understand that a “substance delivery system” can be implemented as a combustible aerosol provision system, a non-combustible aerosol provision system or an aerosol-free delivery system. Combustible aerosol provision systems include cigarettes, cigarillos, cigars, and tobacco for pipes or for roll-your-own or for make-your-own cigarettes (whether based on tobacco, tobacco derivatives, expanded tobacco, reconstituted tobacco, tobacco substitutes or other smokeable material). Aerosol-free delivery systems are those that deliver the at least one substance to a user orally, nasally, transdermally or in another way without forming an aerosol, including but not limited to, lozenges, gums, patches, articles comprising inhalable powders, vapour provision systems that provide vapour as opposed to aerosol, and oral products such as oral tobacco which includes snus or moist snuff, wherein the at least one substance may or may not comprise nicotine.

[0046] The term "alkyl" refers to a monoradical of a saturated straight or branched hydrocarbon. Preferably, the alkyl group comprises from 1 to 6, i.e., 1, 2, 3, 4, 5 or 6, carbon atoms, such as 1 to 6, 1 to 4 or 1 to 2 carbon atoms. Exemplary alkyl groups include methyl, ethyl, propyl, iso-propyl (also called 2-propyl or 1 methylethyl), butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, sec-pentyl, neo-pentyl, 1,2-dimethylpropyl, iso-amyl, n-hexyl, iso-hexyl, sechexyl and the like. A "substituted alkyl" means that one or more hydrogen atoms of the alkyl group are replaced with a substituent other than hydrogen (when more than one hydrogen atom is replaced the substituents may be the same or different). In some embodiments, the alkyl is substituted with one or more, such as 1 , 2 or 3, such as 1 or 2.

[0047] The term "alkenyl" refers to a monoradical of an unsaturated straight or branched hydrocarbon having at least one carbon-carbon double bond. Preferably, the alkenyl group has 1, 2 or 3 carbon-carbon double bonds. Preferably, the alkenyl group comprises from 2 to 6 carbon atoms, 2 to 5 carbon atoms 2 to 4 carbon atoms or 2 to 3 carbon atoms. The carboncarbon double bond(s) may be in cis (Z) or trans (E) configuration. Exemplary alkenyl groupsinclude vinyl, 1-propenyl, 2-propenyl (i.e., allyl), 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and the like. A "substituted alkenyl" means that one or more hydrogen atoms of the alkenyl group are replaced with a substituent other than hydrogen (when more than one hydrogen atom is replaced the substituents may be the same or different). In some embodiments, the alkenyl is substituted with one or more, such as 1 , 2 or 3, such as 1 or 2.

[0048] The term "aryl" refers to a monoradical of an aromatic cyclic hydrocarbon. Preferably, the aryl group contains 3 to 14 (e.g., 5, 6, 7, 8, 9, or 10, such as 5, 6, or 10) carbon atoms which can be arranged in one ring (e.g., phenyl) or two or more condensed rings (e.g., naphthyl). Exemplary aryl groups include cyclopropenylium, cyclopentadienyl, phenyl, indenyl, naphthyl, azulenyl, fluorenyl, anthryl, and phenanthryl. Preferably, "aryl" refers to a monocyclic ring containing 6 carbon atoms or an aromatic bicyclic ring system containing 10 carbon atoms. Preferred examples are phenyl and naphthyl. A "substituted aryl" means that one or more (such as 1 to the maximum number of hydrogen atoms bound to an aryl group, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 5 or up to 10, such as between 1 to 5, 1 to 4, or 1 to 3, or 1 or 2) hydrogen atoms of the aryl group are replaced with a substituent other than hydrogen (when more than one hydrogen atom is replaced the substituents may be the same or different). Examples of a substituted aryl include biphenyl, 4-hydroxyphenyl, and methoxyphenyl (i.e., 2-, 3-, or 4-methoxyphenyl).

[0049] The term "keto acid" as used herein, refers to organic compounds that contain a carboxylic acid group and a ketone group. Common types of keto acids include alphaketo acids, or 2-oxoacids, such as pyruvic acid or oxaloacetic acid, having the keto group adjacent to the carboxylic acid; beta-keto acids, or 3-oxoacids, such as acetoacetic acid, having the ketone group at the second carbon from the carboxylic acid; gamma-keto acids, or 4-oxoacids, such as levulinic acid, having the ketone group at the third carbon from the carboxylic acid.

[0050] The term "carboxy-aldehyde" as used herein, refers to organic compounds that contain a carboxylic acid group and an aldehyde group of the formula -CHO.

[0051] The term "polyhydric alcohol" refers to an organic compounds comprising more than one hydroxyl (“-OH”) group, i.e. two or more hydroxyl groups. A polyhydric alcohol molecule with two hydroxyl groups is typically referred to as a “diol”, with three a “triol”, and with four a “tetrol”. General examples include propylene glycol, polyethylene glycol, glycerin, butylene glycol, polyoxyethylene, polypropylene glycol, ethylene glycol, and the like.

[0052] The term "reaction product" means a product from a reaction between two materials, i.e. keto acids or carboxy-aldehydes and polyhydric alcohols. In general, the term "reaction product" will be used herein to refer to acetals and derivatives thereof (e.g. hemiacetals).

[0053] The term "acetal" as used herein, refers to compounds having the structure RIR2C(OR')2(R1t H). The term refers to derivatives of aldehydes (either Ri or R2= H), and derivatives of ketones (neither Ri nor R2= H). Mixed acetals may have different R' groups. Cyclic acetals have the R' groups from the same polyhydric alcohol molecule. For the avoidance of doubt, the term "acetal" encompasses acetals and ketals.

[0054] The term "hemiacetal" as used herein, refers to compounds having the general formula RIR2C(OH)OR' ( R' H ), where Ri, R2is a hydrogen atom or an organic substituent. For the avoidance of doubt, the term "hemiacetal" encompasses hemiacetals and hemiketals.

[0055] As discussed herein the present invention provides a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals and derivatives thereof, the acetals and acetal derivatives being a reaction product of a C3 to C keto acid and a polyhydric alcohol, or a C2to C carboxy-aldehyde and a polyhydric alcohol.CONSUMABLES

[0056] In vaping experience includes, in some embodiments, the desired sensorials of smoke and the building sensorial sensation puff-by-puff to a level of perceived saturation. Nicotine sensation, for example, includes nicotine “hit” (i.e. the physiological response, sometimes referred to as the “buzz”) and impact (i.e. where the user experiences irritation and taste) and is an integral part of the smoking experience.

[0057] Surprisingly the consumable of the present disclosure improved the sensorial experience of an aerosolisable formulation when used in an aerosol provision device as well as the sensorial experience of a vaporisable formulation when used in a vapour provision device. Furthermore, the levels of the compounds in the consumable can be adjusted in order to tailor the flavour intensity to consumer preference. This is beneficial because it maximises the switching and appeal of an aerosol provision system as an alternative to cigarettes or other combustible tobacco products. It also allows the user to add the consumable to a substrate in a vapour provision system and thereby modulate the vapour generated therefrom, e.g. providing the user with increased control of sensorial experience. Along with this range of cigarette smoking sensations, the consumable can be combined with a range of flavours and substrates (e.g. e-liquids, binders, carriers and the like). The consumable can, for example,be used with a flavoured e-liquid (e.g. tobacco, mint or menthol), tobacco extract (either solid or liquid), or any botanical material (e.g. in the form of a gel).

[0058] Hence, the consumable according to the present disclosure may include at least one further component selected from aerosol former materials, active substances, substrate materials, or a combination thereof. Typically these components will depend on the substance delivery system in which the consumable is intended to be used.

[0059] For ease of reference, these and further aspects of the present invention are now discussed under appropriate section headings. However, the teachings under each section are not necessarily limited to each particular section. In other words, particular sections of the description are not to be read in isolation from other sections.

[0060] The ranges provided herein relate to exemplary amounts of each of the components. Each of these ranges may be taken alone or combined with one or more other component range(s) to provide an embodiment of the invention.Acetals

[0061] As is understood by one skilled in the art, acetalisation refers to the organic reaction between an alcohol and an aldehyde or a ketone, proceeding via a hemiacetal intermediate, before resulting in the formation of an acetal (see below).

[0062] Acetalisation is a reversible reaction, where acetals may be hydrolysed to their starting components by treatment with aqueous acid and of water. As will be apparent to those skilled in the art, according to the present invention, the acetal may be present as a mixture of the acetal, hemiacetals, keto acid or carboxy-aldehyde and polyhydric alcohol in varying proportions. In some embodiments, the acetal may further comprise a precursor thereof. Insome embodiments, the acetal may further comprise a precursor thereof, where the precursor is a hemiacetal. In this embodiment, the hemiacetal precursor is capable of forming the acetal.

[0063] There is provided herein a consumable for an aerosolisable or vaporisable formulation, i.e. a consumable suitable for use in an aerosolisable or vaporisable formulation. In particular, a consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to C keto acid and a polyhydric alcohol, or a C2 to C carboxy-aldehyde and a polyhydric alcohol.

[0064] In some embodiments the one or more acetals are present in an amount of about 0.001 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.01 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.05 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.1 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.2 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.3 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.4 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 0.5 wt% to about 10 wt%, based on the total weight of the consumable. In some embodiments the one or more acetals are present in an amount of about 1 wt% to about 10 wt%, based on the total weight of the consumable.

[0065] In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 1000 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 500 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 100 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 80 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 60 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 40 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 30 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 20 ppm. In some embodiments the one or more acetals are present in the consumable in an amount of 1 ppm to about 10 ppm.

[0066] In some embodiments the one or more acetal comprises a reaction product of a C3 to Cis keto acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C keto acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C14 keto acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C12 keto acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C10 keto acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C3 to Cs keto acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C3 to Ce keto acid and a polyhydric alcohol.

[0067] In some embodiments the one or more acetal comprises a reaction product of a C3 to Cis keto acid and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C keto acid and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C14 keto acid and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C12 keto acid and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C3 to C10 keto acid and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C3 to Cs keto acid and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C3 to Cs keto acid and glycerol.

[0068] In some embodiments the one or more acetal comprises a reaction product of levulinic acid and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of levulinic acid and glycerol. In some embodiments the one or more acetal consists essentially of a reaction product of levulinic acid and glycerol. In some embodiments the one or more acetal consists of a reaction product of levulinic acid and glycerol.

[0069] In some embodiments the keto acids are selected from alpha-keto acids, beta-keto acids, gamma-keto acids and combinations thereof. In some embodiments the keto acids are selected from alpha-keto acids, gamma-keto acids and combinations thereof. In some embodiments the keto acids are selected from alpha-keto acids. In some embodiments the keto acids are selected from beta-keto acids. In some embodiments the keto acids are selected from gamma-keto acids.

[0070] In some embodiments the keto acids are selected from levulinic acid, pyruvic acid, oxaloacetic acid, acetoacetic acid, beta-hydroxybutyric acid, alpha-ketoglutaric acid, alphaketobutyric acid and combinations thereof. In some embodiments the keto acids are selected from levulinic acid and pyruvic acid. In some embodiments the keto acid is levulinic acid.

[0071] In some embodiments the keto acids are selected from levulinic acid, pyruvic acid, alpha-ketoglutaric acid and combinations thereof. In some embodiments the keto acid is pyruvic acid. In some embodiments the keto acid is alpha-ketoglutaric acid.

[0072] In some embodiments the one or more acetal comprises a reaction product of a C2 to Cis carboxy-aldehyde and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C carboxy-aldehyde and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C14 carboxy-aldehyde and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C12 carboxy-aldehyde and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C10 carboxy-aldehyde and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C2 to Cs carboxy-aldehyde and a polyhydric alcohol. In some embodiments the one or more acetal comprises a reaction product of a C2 to Cs carboxyaldehyde and a polyhydric alcohol.

[0073] In some embodiments the one or more acetal comprises a reaction product of a C2 to Cis carboxy-aldehyde and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C2 to Cw carboxy-aldehyde and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C14 carboxy-aldehyde and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C12 carboxy-aldehyde and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C2 to C10 carboxy-aldehyde and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C2 to Cs carboxy-aldehyde and glycerol. In some embodiments the one or more acetal comprises a reaction product of a C2 to Ce carboxyaldehyde and glycerol.

[0074] In some embodiments the C2 to C carboxy-aldehyde are selected from glyoxylic acid, formylacetic acid, oxobutanoic acid, oxoheptanoic acid, oxohexanoic acid, oxoheptanoic acid, oxoocttanoic acid, formylbenzoic acid and combinations thereof. In some embodiments the C2 to Cis carboxy-aldehyde are selected from glyoxylic acid, formylacetic acid, 4-oxobutanoic acid, 5-oxoheptanoic acid, 6-oxohexanoic acid, 7-oxoheptanoic acid, 8-oxoocttanoic acid, 4-formylbenzoic acid and combinations thereof.

[0075] In some embodiments the C2 to Cw carboxy-aldehyde are selected from glyoxlic acid, formylacetic acid, 4-oxobutanoic acid, 5-oxoheptanoic acid, 6-oxohexanoic acid, 7-oxoheptanoic acid, 8-oxoocttanoic acid.

[0076] In some embodiments the C2 to C carboxy-aldehyde are selected from glyoxylic acid, formylbenzoic acid and combinations thereof. In some embodiments the C2 to C carboxyaldehyde are selected from glyoxylic acid, 4-formylbenzoic acid and combinations thereof. In some embodiments the C2 to C carboxy-aldehyde is glyoxylic acid. In some embodiments the C2 to C carboxy-aldehyde is formylbenzoic acid. In some embodiments the C2 to C carboxy-aldehyde is 4-formylbenzoic acid.

[0077] The consumable according to any preceding embodiment, wherein the keto acid or carboxy-aldehyde is represented by formula (I):wherein n is an integer from 0 to 6;R1 is selected from H, CI-B alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa; andeach R2 is independently selected from H, OH, CH(O), C(O)Ra, or CI-B alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra;Rais Ci-6 alkyl or alkenyl, optionally substituted by OH, or OH; provided that at least one CH(O) group is present for the carboxy-aldehyde, and the total number of carbon atoms is from 2 to 18 for the carboxy-aldehyde and from 3 to 18 for the keto acid.

[0078] The consumable according to any preceding embodiment, wherein the keto acid or carboxy-aldehyde is represented by formula (la):wherein M is a C3-14 aryl optionally substituted by CI-B alkyl, CI-B alkenyl, oxo, OH, CH(O) or C(O)Ra, C(O)OH or C(O)ORa;R1 is selected from H, CI-B alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa; andeach Rais H, OH, CI-B alkyl or alkenyl, optionally substituted by OH, CI-B alkyl or alkenyl, oxo, OH, CH(O) C(O)OH or C(O)Ra, orC(O)ORa;provided that at least one CH(O) group is present for the carboxy-aldehyde, and the total number of carbon atoms is from 2 to 18 for the carboxy-aldehyde and from 3 to 18 for the keto acid.

[0079] In some embodiments n is an integer from 0 to 6. In some embodiments n is an integer from 0 to 5. In some embodiments n is an integer from 0 to 4. In some embodiments n is an integer from 0 to 3. In some embodiments n is an integer from 0 to 2. In some embodiments n is 0 or 1. In some embodiments n is 0. In some embodiments n is 1. In some embodiments n is 2. In some embodiments n is 3. In some embodiments n is 4. In some embodiments n is 5. In some embodiments n is 6.

[0080] In some embodiments Ri is H. In some embodiments Ri is Ci-e alkyl or alkenyl optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa. In some embodiments Ri is C1.5 alkyl or alkenyl optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa. In some embodiments Ri is C1.4 alkyl or alkenyl optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa. In some embodiments Ri is C1.3 alkyl or alkenyl optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa. In some embodiments Ri is C1.2 alkyl or alkenyl optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa.

[0081] In some embodiments R2is H. In some embodiments R2is independently selected from OH, CH(O), C(O)Ra, or Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra. In some embodiments R2is independently selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra. In some embodiments R2is independently selected from C1.5 alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra. In some embodiments R2is independently selected from C1.4 alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra. In some embodiments R2is independently selected from C1.3 alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra. In some embodiments R2is independently selected from Ci.2alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O) Ra.

[0082] In some embodiments Rais OH. In some embodiments Rais Ci-e alkyl or alkenyl, optionally substituted by OH. In some embodiments Rais C1.5 alkyl or alkenyl, optionally substituted by OH. In some embodiments Rais C1.4 alkyl or alkenyl, optionally substituted by OH. In some embodiments Rais C1.3 alkyl or alkenyl, optionally substituted by OH. In some embodiments Rais Ci-2alkyl or alkenyl, optionally substituted by OH.

[0083] In some embodiments M is a C3-10 aryl optionally substituted by Ci-e alkyl, Ci-e alkenyl, oxo, OH, CH(O) or C(O)Ra, C(O)OH or C(O)ORa. In some embodiments M is a C5-10 aryloptionally substituted by Ci-e alkyl, Ci-e alkenyl, oxo, OH, CH(O) or C(O)Ra, C(O)OH or C(O)ORa. In some embodiments M is a C5-6 aryl optionally substituted by Ci-e alkyl, Ci-e alkenyl, oxo, OH, CH(O) or C(O)Ra, C(O)OH or C(O)ORa. In some embodiments M is a C5 aryl optionally substituted by Ci-e alkyl, Ci-e alkenyl, oxo, OH, CH(O) or C(O)Ra, C(O)OH or C(O)ORa. In some embodiments M is a Ce aryl optionally substituted by Ci-e alkyl, Ci-e alkenyl, oxo, OH, CH(O) or C(O)Ra, C(O)OH or C(O)ORa. In some embodiments M is a C3-10 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments M is a C5-10 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments M is a C5-6 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments M is a C5 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments M is a Ce aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments M is a benzene ring.

[0084] In some embodiments M is a C5 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH, and R1 is H. In some embodiments M is a Ce aryl optionally substituted by Ci-e alkyl, OH, C(O)OH, and R1 is H.

[0085] In some embodiments the one or more acetals are selected from acyclic acetals, cyclic acetals or combinations thereof. In some embodiments the one or more acetals are selected from acyclic acetals or cyclic acetals. In some embodiments the one or more acetals comprise acyclic acetals. In some embodiments the one or more acetals comprise cyclic acetals. In some embodiments the one or more acetals consist essentially of acyclic acetals. In some embodiments the one or more acetals consist essentially of cyclic acetals. In some embodiments the one or more acetals are acyclic acetals. In some embodiments the one or more acetals are cyclic acetals.

[0086] In some embodiments the one or more acetals are selected from acid substituted acyclic acetals, acid substituted cyclic acetals or combinations thereof. In some embodiments the one or more acetals are selected from acid substituted acyclic acetals or acid substituted cyclic acetals. In some embodiments the one or more acetals comprise acid substituted acyclic acetals. In some embodiments the one or more acetals comprise acid substituted cyclic acetals. In some embodiments the one or more acetals consist essentially of acid substituted acyclic acetals. In some embodiments the one or more acetals consist essentially of acid substituted cyclic acetals. In some embodiments the one or more acetals are acid substituted acyclic acetals. In some embodiments the one or more acetals are acid substituted cyclic acetals.

[0087] In some embodiments the one or more acetals comprise compounds selected from substituted 1,3-dioxanes, 1,3-dioxolanes or mixtures thereof. In some embodiments the oneor more acetals are selected from substituted 1,3-dioxanes, 1,3-dioxolanes or mixtures thereof. In some embodiments the one or more acetals are selected from substituted 1,3-dioxanes or 1,3-dioxolanes. In some embodiments the one or more acetals comprise substituted 1,3-dioxanes. In some embodiments the one or more acetals comprise substituted 1.3-dioxolanes. In some embodiments the one or more acetals consist essentially of substituted 1,3-dioxanes. In some embodiments the one or more acetals consist essentially of substituted 1,3-dioxolanes. In some embodiments the one or more acetals are substituted 1.3-dioxanes. In some embodiments the one or more acetals are substituted 1,3-dioxolanes. In some embodiments the one or more acetals comprise compounds selected from acid substituted 1,3-dioxanes, 1,3-dioxolanes or mixtures thereof. In some embodiments the one or more acetals are selected from acid substituted 1,3-dioxanes, 1,3-dioxolanes or mixtures thereof. In some embodiments the one or more acetals are selected from acid substituted 1 ,3-dioxanes or 1,3-dioxolanes. In some embodiments the one or more acetals comprise acid substituted 1,3-dioxanes. In some embodiments the one or more acetals comprise acid substituted 1,3-dioxolanes. In some embodiments the one or more acetals consist essentially of acid substituted 1,3-dioxanes. In some embodiments the one or more acetals consist essentially of acid substituted 1,3-dioxolanes. In some embodiments the one or more acetals are acid substituted 1,3-dioxanes. In some embodiments the one or more acetals are acid substituted 1 ,3-dioxolanes.

[0088] In some embodiments the one or more acetals may be a compound represented by formula (II):wherein m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;R3is H and R4is selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb; orR3and R4are independently selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb;each of Rs and Re are independently selected from H, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rb is selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R3, R4, Rs, Re, Rb and / or Rcis substituted by C(O)OH.

[0089] In one aspect there is provided a formulation for a substance delivery system, wherein the formulation comprises polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (Ila):wherein m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;R3 is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb; orR3 and R4 are independently selected from H, OH, CH(O), C(O)OH, C(O)Rb, or C(O)ORb, Ci- 6 alkyl, Ci-6 alkenyl or C3-14 aryl, wherein the alkyl, alkenyl and / or aryl moieties are optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb; each of R5and R6are independently selected from H, OH, C1.6 alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb; each Rbis selected from H, OH, C1.6 alkyl or alkenyl, optionally substituted by C1.6 alkyl or alkenyl, oxo, OH, CH(O) C(O)OH or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from H, OH, C1.6 alkyl or alkenyl, optionally substituted by C1.6 alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R3, R4, Rs, Re, b and / or Rcis substituted by C(O)OH.

[0090] In some embodiments m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;Rs is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb;each of R5 and Re are independently selected from H, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rbis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R5, Re, Rband / or Rcis substituted by C(O)OH.

[0091] In some embodiments m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;R3 and R4 are independently selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb;each of R5 and Re are independently selected from H, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rbis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R5, Re, Rband / or Rcis substituted by C(O)OH.

[0092] In some embodiments m is an integer from 0 to 5. In some embodiments m is an integer from 0 to 4. In some embodiments m is an integer from 0 to 3. In some embodiments m is an integer from 0 to 2. In some embodiments m is 1 or 2. In some embodiments m is 0 or 1. In some embodiments m is 1. In some embodiments m is 2.

[0093] In some embodiments X is independently selected from CH2, CRbRc, or O. In some embodiments X is independently selected from CH2or O. In some embodiments X is independently selected from CHRbor O. In some embodiments X is independently selected from CRbRcor O. In some embodiments X is independently selected from CH2. In some embodiments X is CH2, CHRb, CRbRc, or O. In some embodiments X is CH2. In some embodiments X is CHRb. In some embodiments X is CRbRc. In some embodiments X is O.

[0094] In some embodiments R3 is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by C(O)ORb. In some embodiments R3 is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by C(O)OH. In some embodiments R3 is H and R4 is selected from C1.6 alkyl or alkenyl, substituted by C(O)ORb. In some embodiments R3 is H and R4 isselected from Ci-e alkyl or alkenyl, substituted by C(O)OH. In some embodiments R3 is H and R4 is C1.6 alkyl, optionally substituted by C(O)ORb. In some embodiments R3 is H and R4 is Ci- 6 alkyl, optionally substituted by C(O)OH. In some embodiments R3 is H and R4 is Ci-e alkyl, substituted by C(O)ORb. In some embodiments R3 is H and R4 is Ci-e alkyl, substituted by C(O)OH.

[0095] In some embodiments R5 and Re are independently selected from H, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, or OH, or OH. In some embodiments R5 and Re are independently selected from H, Ci-e alkyl, optionally substituted by Ci-e alkyl or alkenyl, or OH, or OH. In some embodiments R5 and Re are independently selected from H, Ci-e alkyl, substituted by Ci-e alkyl or alkenyl, or OH, or OH. In some embodiments R5 and Re are independently selected from H, Ci-e alkyl, optionally substituted by OH, or OH. In some embodiments R5 and Re are independently selected from H, Ci-e alkyl, substituted by OH, or OH. In some embodiments R5 is H and Re is Ci-e alkyl substituted by OH.

[0096] In some embodiments Rb is selected from Ci-e alkyl optionally substituted by Ci-e alkyl or alkenyl, OH, or OH. In some embodiments Rb is selected from Ci-e alkyl optionally substituted by Ci-e alkyl, or OH, or OH. In some embodiments Rb is selected from Ci-e alkyl optionally substituted by OH, or OH. In some embodiments Rbis selected from C1.6 alkyl substituted by C1.6 alkyl or alkenyl, OH, or OH. In some embodiments Rbis selected from Ci.6 alkyl substituted by C1.6 alkyl, or OH, or OH. In some embodiments Rbis selected from C1.6 alkyl substituted by OH, or OH. In some embodiments Rbis selected from C1.6 alkyl, or OH. In some embodiments Rb is Ci-e alkyl. In some embodiments Rb is OH.

[0097] In some embodiments Rcis selected from C1.6 alkyl optionally substituted by C1.6 alkyl or alkenyl, OH, or OH. In some embodiments Rcis selected from C1.6 alkyl optionally substituted by C1.6 alkyl, or OH, or OH. In some embodiments Rcis selected from C1.6 alkyl optionally substituted by OH, or OH. In some embodiments Rcis selected from C1.6 alkyl substituted by Ci-e alkyl or alkenyl, OH, or OH. In some embodiments Rcis selected from Ci-e alkyl substituted by Ci-e alkyl, or OH, or OH. In some embodiments Rcis selected from Ci-e alkyl substituted by OH, or OH. In some embodiments Rcis selected from Ci-e alkyl, or OH. In some embodiments Rcis C1.6 alkyl. In some embodiments Rcis OH.

[0098] In some embodiments R3and R4are independently selected from H and / or C3-14 aryl optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb. In some embodiments R3 and R4 are independently selected from H and / or C3-10 aryl optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb. In some embodiments R3 and R4 are independently selected from H and / or C5-10aryl optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb. In some embodiments R3 and R4 are independently selected from H and / or C5-6 aryl optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb. In some embodiments R3 and R4 are independently selected from H and / or C5 aryl optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb. In some embodiments R3 and R4 are independently selected from H and / or Ce aryl optionally substituted by Ci-e alkyl or alkenyl, oxo, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb. In some embodiments R3 is H and R4 is a C3-14 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments R3 is H and R4 is a C3-10 aryl optionally substituted by Ci-6 alkyl, OH, C(O)OH. In some embodiments R3 is H and R4 is a C5-10 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments R3 is H and R4 is a C5-6 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments R3 is H and R4 is a C5 aryl optionally substituted by Ci-e alkyl, OH, C(O)OH. In some embodiments R3is H and R4 is a Ce aryl optionally substituted by Ci-e alkyl, OH, C(O)OH.

[0099] In some embodiments according to formula (Ila), R3 is H and R4 is Cs- aryl optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb, m is 1 or 2, X is CH2and / or CRbRc, R5 is H and R6is H, OH, or Ci-e alkyl substituted by OH. In some embodiments according to formula (Ila), R3is H and R4is Cs-earyl optionally substituted by Ci.6 alkyl or alkenyl, OH, CH(O) or C(O)Rb, C(O)OH or C(O)ORb, m is 1 or 2, X is CH2and / or CHOH, R5is H and R6is H, OH or Ci-e alkyl substituted by OH.

[0100] In some embodiments m is 1, X is CH2, R3 is H and R4 is Ci-e alkyl, substituted by C(O)OH, R5is H and R6is Ci-e alkyl substituted by OH.

[0101] In some embodiments m is 2, one X group is CH2and the second X group is CHOH, R3is H and R4is Ci-e alkyl, substituted by C(O)OH, R5is H and R6is H.

[0102] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 3-(5-hydroxy-2-methyl-1,3-dioxan-2-yl)propanoic acid, 3-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)propanoic acid and combinations thereof.3 (5--hydroxy--2- ethyl- 1 ,3-dioxan-2-yl)propanoic acid3-(4-(hydroxymethyl)-2-methyl-1 ,3-dioxolan-2-yl)propanoic acid

[0103] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 3-(5-hydroxy-2-methyl-1,3-dioxan-2-yl)propanoic acid, 3-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)propanoic acid, 2-(4-carboxyphenyl)-1,3-dioxolane-4-methanol, 2-(4-carboxyphenyl)-1 ,3-dioxan-5-ol, (2-carboxy-1 ,3-dioxolan-4-yl)methanol, 2-carboxy-1 ,3-dioxan-5-ol, 4-(hydroxymethyl)-2-methyl-1,3-dioxolane-2-carboxylic acid, 5-hydroxy-2-methyl-1,3-dioxane-2-carboxylic acid, 2-(5-methyl-1,3-dioxan-2-yl)propanoic acid, 4-(2-hydroxy-5-methyl-1 ,3-dioxan-2-yl)-2-oxobutanoic acid, 4-(2-hydroxy-5-methyl-1 ,3-dioxan-2-yl)-4-oxobutanoic acid, 2-(2-carboxyethyl)-5-methyl-1,3-dioxane-2-carboxylic acid or combinations thereof.

[0104] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 3-(5-hydroxy-2-methyl-1 ,3-dioxan-2-yl)propanoic acid.

[0105] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 3-(4-(hydroxymethyl)-2-methyl-1 ,3-dioxolan-2-yl)propanoic acid.

[0106] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 2-(4-carboxyphenyl)-1,3-dioxolane-4-methanol, 2-(4-carboxyphenyl)-1,3-dioxan-5-ol or combinations thereof.

[0107] In some embodiments the one or more acetals comprise, consist essentially of, or consist of (2-carboxy-1,3-dioxolan-4-yl)methanol, 2-carboxy-1,3-dioxan-5-ol or combinations thereof.

[0108] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 4-(hydroxymethyl)-2-methyl-1,3-dioxolane-2-carboxylic acid, 5-hydroxy-2-methyl- 1.3-dioxane-2-carboxylic acid or combinations thereof.

[0109] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 2-(5-methyl-1 ,3-dioxan-2-yl)propanoic acid.

[0110] In some embodiments the one or more acetals comprise, consist essentially of, or consist of 4-(2-hydroxy-5-methyl-1,3-dioxan-2-yl)-2-oxobutanoic acid, 4-(2-hydroxy-5-methyl- 1.3-dioxan-2-yl)-4-oxobutanoic acid, 2-(2-carboxyethyl)-5-methyl-1 ,3-dioxane-2-carboxylic acid or combinations thereof.Polvhvdric alcohols

[0111] As described herein, the one or more acetal are formed as a reaction product of a keto acid and polyhydric alcohols, or carboxy-aldehydes and polyhydric alcohols. Polyhydric alcohols suitable for use in aerosolisable or vaporisable formulations would be known to the person skilled in the art. However, in some embodiments, the polyhydric alcohols may be selected from diols, triols, tetrols and combinations thereof. In some embodiments, the polyhydric alcohols may be selected from diols. In some embodiments, the polyhydric alcohols may be selected from triols. In some embodiments, the polyhydric alcohols may be selected from tetrols.

[0112] In some embodiments, the polyhydric alcohols may be selected from monosaccharides, disaccharides, polysaccharides, esters, diesters, fatty acid esters, glycol esters, citric acid esters, sugar alcohol esters, choline derivatives, aprotic imidazoliums, diols, sugar alcohols, straight-chain alkanes, polysorbates, polyethers and combinations thereof.

[0113] In some embodiments, the polyhydric alcohols may be selected from one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, propylene carbonate, maltitol, propylene glycol caprylate, diisoamyl adipate, ethyl octanoate, “L-Lysine, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium (1:1)”, cholin acetate, 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium acetate, 1-ethyl-3-methylimidazolium propionate, 1-ethyl-3-methylimidazolium octanoate, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1,3-butanediol, isopropyl myristate, 2,3-butanediol, D-mannitol, hexadecane, 1,3-propanediol, decyl glucoside, triethylene glycol bis(2-ethyl hexanoate), Bis(2-ethylhexyl) adipate, acetyl triethyl citrate, acetyl trihexyl citrate, acetyl trioctyl citrate, triethyl 2-(1 ,2-dioxopropoxy)propane-1 ,2,3-tricarboxylate, “methacrylic acid;triethyl-2-hydroxypropane-1 ,2,3-tricarboxylate”, “sodium;triethyl-2-hydroxypropane-1 ,2,3-tricarboxylate, “but-3-enoic acid;acetyl tributyl citrate”, acetyl triethyl citrate, bis(2-ethylhexyl) adipate, polyoxyethylene (20) sorbitan monooleate, isopropyl palmitate, sorbitan trioleate, sorbitan monolaurate, sorbitan tristearate, isopropyl isostearate, and polyethylene glycol 600.

[0114] In some embodiments, the polyhydric alcohols may be selected from one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid and propylene carbonate. In some embodiments, the polyhydric alcohols may further comprise propylene glycol. In some cases, the polyhydric alcohols comprises, consists essentially of or consists of glycerol, ora mixture of glycerol and propylene glycol.

[0115] In some embodiments, the polyhydric alcohols may be selected from one or more of maltitol, propylene glycol, caprylate, “L-Lysine, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium (1:1)”, cholin acetate, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1,3-butanediol, 2,3-butanediol, 1,3-propanediol, triethyl citrate, decyl glucoside, triethylene glycol bis(2-ethylhexanoate), acetyl trihexyl citrate, sorbitan monooleate, sorbitan trioleate, sorbitan monolaurate, sorbitan tristearate, and polyethylene glycol 600.

[0116] In some embodiments, the polyhydric alcohols may be selected from glycerol, propylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, maltitol, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1 ,3-butanediol, 2,3-butanediol, D-mannitol, 1,3-propanediol, decyl glucoside, polyoxyethylene (20) sorbitan monooleate, sorbitan monolaurate and combinations thereof. In one aspect, the polyhydric alcohols may be selected from glycerol, propylene glycol and combinations thereof. In one aspect, the polyhydric alcohol is glycerol. In one aspect, the polyhydric alcohol is propylene glycol.

[0117] In one aspect, the polyhydric alcohols may be selected from glycerol, 2-methyl-1,3-propanediol, propylene glycol and combinations thereof. In one aspect, the polyhydric alcohols may be selected from glycerol, 2-methyl-1,3-propanediol combinations thereof. In one aspect, the polyhydric alcohol is 2-methyl-1,3-propanediol.

[0118] In some embodiments, polyhydric alcohol is present in an amount of from 10%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 20%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 30%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 40%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 95%w / w based on the total weight of the consumable.

[0119] In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 85%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 80%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 75%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 60%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 65%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 50%w / w to 60%w / w based on the total weight of the consumable.

[0120] In some embodiments, polyhydric alcohol is present in an amount of from 55%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 60%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 65%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 70%w / w to 90%w / w based on the totalweight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 75%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 80%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of from 85%w / w to 90%w / w based on the total weight of the consumable.

[0121] In some embodiments, polyhydric alcohol is present in an amount of at least 10%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 20%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 30%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 40%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 50%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 50%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 55%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 60%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 65%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 70%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 75%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 80%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 85%w / w based on the total weight of the consumable. In some embodiments, polyhydric alcohol is present in an amount of at least 90%w / w based on the total weight of the consumable.

[0122] In some embodiments, glycerol is present in an amount of from 10%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 20%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 30%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 40%w / w to 95%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 95%w / w based on the total weight of the consumable.T1

[0123] In some embodiments, glycerol is present in an amount of from 50%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 85%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 80%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 75%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 60%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 65%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 50%w / w to 60%w / w based on the total weight of the consumable.

[0124] In some embodiments, glycerol is present in an amount of from 55%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 60%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 65%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 70%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 75%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 80%w / w to 90%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of from 85%w / w to 90%w / w based on the total weight of the consumable.

[0125] In some embodiments, glycerol is present in an amount of at least 10%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 20%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 30%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 40%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 50%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 50%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 55%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 60%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 65%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 70%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 75%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in anamount of at least 80%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 85%w / w based on the total weight of the consumable. In some embodiments, glycerol is present in an amount of at least 90%w / w based on the total weight of the consumable.Aerosol former material

[0126] In some embodiments the consumable further comprises an aerosol former material. The aerosol former material may comprise one or more constituents capable of forming an aerosol. The consumable may comprise aerosol former material in an amount of at least 70 wt% on the basis of the total weight of the consumable. In some embodiments the consumable comprises aerosol former material in an amount of at least 80 wt% on the basis of the total weight of the consumable. In some embodiments the consumable comprises aerosol former material in an amount of at least 90 wt% on the basis of the total weight of the consumable. In some embodiments the consumable comprises aerosol former material in an amount of at least 95 wt% on the basis of the total weight of the consumable. In some embodiments the aerosol former material is present in an amount of about 50 to about 99 wt% on the basis of the total weight of the consumable. In some embodiments the aerosol former material is present in an amount of about 60 to about 98 wt% on the basis of the total weight of the consumable. In some embodiments the aerosol former material is present in an amount of about 70 to about 95 wt% on the basis of the total weight of the consumable.

[0127] In some embodiments, the aerosol former material may, in addition to the polyhydric alcohol (e.g. glycerol) contained within the consumable, comprise one or more further constituents capable of forming an aerosol. In some embodiments, the aerosol former material may further comprise one or more compounds selected from diols, triols, tetrols and combinations thereof. In some embodiments, the aerosol former material may further comprise one or more compounds selected from diols. In some embodiments, the aerosol former material may further comprise one or more compounds selected from triols. In some embodiments, the aerosol former material may further comprise one or more compounds selected from tetrols.

[0128] In some embodiments, the aerosol former material may further comprise one or more compounds selected from monosaccharides, disaccharides, polysaccharides, esters, diesters, fatty acid esters, glycol esters, citric acid esters, sugar alcohol esters, choline derivatives, aprotic imidazoliums, diols, sugar alcohols, straight-chain alkanes, polysorbates, polyethers and combinations thereof.

[0129] In some embodiments, the aerosol former material may further comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, propylene carbonate, maltitol, propylene glycol caprylate, diisoamyl adipate, ethyl octanoate, “L-Lysine, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium (1:1)”, cholin acetate, 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium acetate, 1-ethyl-3-methylimidazolium propionate, 1-ethyl-3-methylimidazolium octanoate, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1,3-butanediol, isopropyl myristate, 2,3-butanediol, D-mannitol, hexadecane, 1,3-propanediol, decyl glucoside, triethylene glycol bis(2-ethyl hexanoate), Bis(2-ethylhexyl) adipate, acetyl triethyl citrate, acetyl trihexyl citrate, acetyl trioctyl citrate, triethyl 2-(1 ,2-dioxopropoxy)propane-1 ,2,3-tricarboxylate, “methacrylic acid;triethyl-2-hydroxypropane-1 ,2,3-tricarboxylate”, “sodium;triethyl-2-hydroxypropane-1 ,2,3-tricarboxylate, “but-3-enoic acid;acetyl tributyl citrate”, acetyl triethyl citrate, bis(2-ethylhexyl) adipate, polyoxyethylene (20) sorbitan monooleate, isopropyl palmitate, sorbitan trioleate, sorbitan monolaurate, sorbitan tristearate, isopropyl isostearate, and polyethylene glycol 600.

[0130] In some embodiments, the aerosol former material comprises, consists essentially of or consists of 2-methyl-1 ,3-propanediol.

[0131] In some embodiments, the aerosol former material may further comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid and propylene carbonate. In some embodiments, the aerosol former material may further comprise propylene glycol. In some cases, the aerosol former material comprises, consists essentially of or consists of glycerol, ora mixture of glycerol and propylene glycol.

[0132] In some embodiments, the aerosol former material may further comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid and propylene carbonate. In some embodiments, the aerosol former material may further comprise propylene glycol. In some embodiments, the aerosol former material may further comprise 2-methyl-1,3-propanediol.

[0133] In some embodiments, the aerosol former material may comprise one or more of maltitol, propylene glycol, caprylate, “L-Lysine, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium (1:1)”, cholin acetate, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1,3-butanediol, 2,3-butanediol, 1,3-propanediol, triethyl citrate, decyl glucoside, triethylene glycol bis(2-ethylhexanoate), acetyl trihexyl citrate, sorbitan monooleate, sorbitan trioleate, sorbitan monolaurate, sorbitan tristearate, and polyethylene glycol 600.

[0134] In some embodiments, the aerosol former material comprises a mixture of glycerol and propylene glycol in a weight ratio of glycerol to propylene glycol of about 3:1 to 1:3, about 2:1 to 1:2, about 1.5:1 to 1:1.5, about 55:45 to 45:55, or about 45:55.Substrate material

[0135] In some embodiments the consumable comprises a substrate material. The substrate material may comprise a carrier material, a porous material, or a combination thereof. By the term “substrate material” is therefore meant a substance or material which supports or otherwise carries the compounds in the consumable, but is not an aerosol former material. The substrate material may be a solid, liquid or gel. In various embodiments of the present disclosure, the substrate material is a solid or a gel.

[0136] In some embodiments the carrier material may comprise one or more solvents. In some embodiments, the carrier material may comprise one or more solvents. By referring to one or more solvents forming part of the carrier material for the active substances, it is meant that the solvent may alter the assimilation, homogenisation, dissolution etc of the one or more active substances. In some embodiments, the carrier material comprises of at least about 30%w / w of one or more solvents. In some embodiments, the carrier material comprises of at least about 40%w / w of one or more solvents. In some embodiments, the carrier material comprises of at least about 50%w / w of one or more solvents. In some embodiments, the carrier material comprises of at least about 60%w / w of one or more solvents. In some embodiments, the carrier material comprises of at least about 70%w / w of one or more solvents. In some embodiments, the carrier material comprises of at least about 80%w / w of one or more solvents. In some embodiments, the carrier material comprises of at least about 90%w / w of one or more solvents. In some embodiments, the carrier material consists of one or more solvents.

[0137] In some embodiments, the carrier material comprises of from about 30%w / w to 100%w / w of one or more solvents. In some embodiments, the carrier material comprises offrom about 40%w / w to 100%w / w of one or more solvents. In some embodiments, the carrier material comprises of from about 50%w / w to 100%w / w of one or more solvents. In some embodiments, the carrier material comprises of from about 60%w / w to 100%w / w of one or more solvents. In some embodiments, the carrier material comprises of from about 70%w / w to 100%w / w of one or more solvents. In some embodiments, the carrier material comprises of from about 80%w / w to 100%w / w of one or more solvents. In some embodiments, the carrier material comprises of from about 90%w / w to 100%w / w of one or more solvents.

[0138] In some embodiments, the one or more solvents are selected from the group consisting of aliphatic alcohols, aromatic alcohols and medium chain triglycerides (MCTs). In some embodiments the aliphatic alcohol is ethanol. In some embodiments the aromatic alcohol is benzyl alcohol.

[0139] In some embodiments, the substrate material comprises a porous material. The porous material may comprise a sponge material, a fibrous material or combinations thereof. The sponge material may be formed of polyvinyl chloride, polyethylene, polyurethane, polyester, or combinations thereof. The fibrous material may be a material selected from the group consisting of paper, tobacco, non-tobacco plant material (e.g. cellulose) or combinations thereof. A cellulose substrate may, for example, comprise cellulose acetate or derivatives thereof including a cellulose acetate filter in a smoking article.

[0140] The substrate may comprise a non-tobacco plant material including cereal grains (e.g., maize, oat, barley, rye, buckwheat, and the like), sugar beet (e.g., FIBREX® brand filler available from International Fiber Corporation), bran fiber, and mixtures thereof. Non-limiting examples of derivatives of non-tobacco plant material include starches (e.g., from potato, wheat, rice, corn), natural cellulose, and modified cellulosic materials. In some embodiments, the non-tobacco plant material substrate comprises a starch, a cellulose material, or both. A cellulose material may, for example, be used to enhance certain organoleptic properties such as texture and mouthfeel, enhancing cohesiveness or compressibility of the consumable for oral use.

[0141] In some embodiments, a container or package containing the consumable defined herein is provided, preferably wherein the container or package is a pouched oral product comprising a saliva permeable pouch, or a cartridge for an aerosol provision system.

[0142] In some embodiments, a substance delivery system comprising the consumable defined herein is provided. In some embodiments, a substance delivery system comprising the container or package defined herein is provided.

[0143] The substance delivery system of claim 17, wherein the system is a combustible aerosol provision system, a non-combustible aerosol provision system or an aerosol-free delivery system.

[0144] In some embodiments, the cellulose material may be microcrystalline cellulose (mcc). The mcc may be synthetic or semi-synthetic, or it may be obtained entirely from natural celluloses. The cellulose derivative may, for example, be present from about 10 to 80 % by weight of the consumable. In some embodiments, the cellulose substrate, e.g. the cellulose derivative substrate, is present from about 10 to 70% by weight of the consumable. When a cellulose substrate is present, the consumable may comprise no more than about 10% by weight of a tobacco material, excluding any nicotine present, based on the total weight of the consumable. In various embodiments the consumable comprising a non-tobacco plant material substrate (e.g. cellulose) includes no more than about 5% by weight of a tobacco material, excluding any nicotine present, based on the total weight of the consumable.

[0145] The tobacco material, whether included in addition to the non-plant material substrate or used as a substrate itself, may be prepared from any type or form of tobacco. The present disclosure is not limited in this respect. Generally, the tobacco material is obtained from a harvested plant of the Nicotiana species. Example Nicotiana species include N. tabacum, N. rustica, N. alata, N. arentsii, N. excelsior, N. forgetiana, N. glauca, N. glutinosa, N. gossei, N. kawakamii, N. knightiana, N. langsdorffi, N. otophora, N. setchelli, N. sylvestris, N. tomentosa, N. tomentosiformis, N. undulata, N. x sanderae, N. africana, N. amplexicaulis, N. benavidesii, N. bonariensis, N. debneyi, N. longiflora, N. maritina, N. megalosiphon, N. occidentalis, N. paniculata, N. plumbaginifolia, N. raimondii, N. rosulata, N. simulans, N. stocktonii, N. suaveolens, N. umbratica, N. velutina, N. wigandioides, N. acaulis, N. acuminata, N. attenuate, N. benthamiana, N. cavicola, N. clevelandii, N. cordifolia, N. corymbose, N. fragrans, N. goodspeedii, N. linearis, N. miersii, N. nudicaulis, N. obtusifolia, N. occidentalis subsp. Hersperis, N. pauciflora, N. petunioides, N. quadrivalvis, N. repanda, N. rotundifolia, N. solanifolia, and N. spegazzinii.

[0146] Various representative other types of plants from the Nicotiana species are set forth in Goodspeed, The Genus Nicotiana, (Chonica Botanica) (1954); US Pat. Nos. 4,660,577 to Sensabaugh, Jr. et al.; 5,387,416 to White et al., 7,025,066 to Lawson et al.; 7,798,153 to Lawrence, Jr. and 8,186,360 to Marshall et al.; each of which is incorporated herein by reference. Descriptions of various types of tobaccos, growing practices and harvesting practices are set forth in Tobacco Production, Chemistry and Technology, Davis et al. (Eds.) (1999), which is incorporated herein by reference.

[0147] Various parts or portions of the plant of the Nicotiana species can be included within a tobacco material as disclosed herein. For example, virtually all of the plant (e.g., the whole plant) can be harvested, and employed as such. Alternatively, various parts or pieces of the plant can be harvested or separated for further use after harvest. For example, the flower, leaves, stem, stalk, roots, seeds, and various combinations thereof, can be isolated for further use or treatment.

[0148] When nicotine is present in the consumable, it may be added or may be inherently present if the substrate material is a tobacco substrate material. In some embodiments the substrate material includes at least one tobacco substrate material. The tobacco substrate material may be solid, liquid or gel. In some embodiments, the tobacco substrate material is solid. The identity of the tobacco is not limited; it can be any type or grade of tobacco and includes any part, such as for example, the leaves or stems of any member of the genus Nicotiana and reconstituted materials thereof. In some embodiments, the tobacco is from the species Nicotiana tabacum. The tobacco substrate material may be from one variety of tobacco or from more than one variety of tobacco. As is known in the art, the latter can be referred to as a blend. Examples of tobacco varieties which may be used include, but are not limited to, Virginia, Burley, Oriental and Rustica tobaccos.

[0149] In some embodiments the tobacco substrate material is a pH-treated tobacco material; pH treatment of tobacco is well known in the art. In general, pH treatment raises the pH of the tobacco material from an acidic pH to an alkaline pH. The tobacco substrate material, including when the tobacco substrate material is a pH-treated tobacco material, can be in any suitable form. In some embodiments, the tobacco substrate material is in the form of particles, beads, granules or the like. The shape and / or size of such particles, beads or granules is not limited in the context of the present invention. The skilled person will be aware of suitable sizes and shapes and the methods by which such sizes and shapes can be achieved.

[0150] In another embodiment, the substrate material includes a non-tobacco substrate material. For example, the substrate material may comprise a fibrous material which is formed of cellulose acetate, polyvinyl alcohol (PVOH), polylactic acid (PLA), polycaprolactone (PCL), poly(i-4 butanediol succinate) (PBS), poly(butylene adipate-co-terephthalate)(PBAT), starch based materials, cotton, aliphatic polyester materials, polysaccharide polymers or a combination thereof.

[0151] In certain embodiments, one or more humectants may be employed in the consumable, for example, with a tobacco or non-plant material substrate. Examples of humectants include, but are not limited to, glycerin, propylene glycol, and the like. Whereincluded, the humectant is typically provided in an amount sufficient to provide desired moisture attributes to the mixture. Further, in some instances, the humectant may impart desirable flow characteristics to the mixture for depositing in a mold. When present, a humectant will typically make up about 5% or less of the weight of the mixture (e.g., from about 0.5 to about 5%). When present, a representative amount of humectant is about 0.1% to about 1% by weight, or about 1% to about 5% by weight, based on the total weight of the mixture.FORMULATION

[0152] In some embodiments there is provided a formulation for a substance delivery system comprising the consumable as defined herein, a carrier or a binder, and an active agent, such as nicotine. In some embodiments the formulation comprises the consumable as defined herein, a carrier and nicotine. In some embodiments, the formulation comprises the consumable as defined herein, a binder and nicotine.

[0153] In other embodiments there is provided a formulation for a substance delivery system comprising the consumable as defined herein, and a substrate material as defined herein.

[0154] In some embodiments the formulation comprises the consumable in an amount of at least about 1% by weight, such as at least about 5 wt% by weight, or even at least about 10 wt% by weight. The consumable may be present in the formulation in an amount of no greater than about 25% by weight, such as no greater than about 20% by weight, or even no greater than about 15 wt% by weight.

[0155] In some embodiments the formulation is an aerosolisable formulation or vaporisable formulation. Reference to aerosolisable or vaporisable formulations directly correspond to the formulations of the present invention.

[0156] In some embodiments the consumable may be present in the formulation in an amount of from about 1% by weight to about 25% by weight, such as from about 5 wt% by weight to about 20% by weight, even from about 10% by weight to about 15% by weight.

[0157] The aerosolisable formulation or vaporisable formulation may take various forms including a gel, a liquid or a solid. In some preferred embodiments, the aerosolisable formulation is a liquid. In other preferred embodiments, the aerosolisable formulation is a gel. In some embodiments the consumable is in the form of a liquid or gel.

[0158] In some embodiments the aerosolisable formulation may be described as an aerosolgenerating material and may be an “amorphous solid”. In some embodiments, the amorphous solid is a “monolithic solid”. The aerosol-generating material may be non-fibrous or fibrous. Insome embodiments, the aerosol-generating material may be a dried gel. The aerosolgenerating material may be a solid material that may retain some fluid, such as liquid, within it. In some embodiments, the retained fluid may be water (such as water absorbed from the surroundings of the aerosol-generating material) or the retained fluid may be solvent (such as when the aerosol-generating material is formed from a slurry). In some embodiments, the solvent may be water.

[0159] In some embodiments, the aerosol generating material may comprise, or be, a collection of individual sheets of material. For example, the aerosol generating material may comprise a sheet comprising a fibrous material comprising a botanical material, such as tobacco material. The sheet may be in the form of a wrapper; it may be gathered to form a gathered sheet or it may be shredded to form a shredded sheet. The shredded sheet may comprise one or more strands or strips of aerosol generating material.

[0160] In some embodiments the aerosol-generating material is in the form of a gathered sheet, elongate strips, or a shredded sheet.

[0161] In some embodiments, the shredded sheet comprises a plurality (e.g. two or more) strands or strips of the aerosol-generating material. Where the shredded sheet comprises a plurality of strands or strips of material, the dimensions of each strand or strip may vary between different strands or strips. For example, the shredded sheet may comprise a first population of strands or strips and a second population of strands or strips, wherein the dimensions of the strands or strips of the first population are different to the dimensions of the strands or strips of the second population. In other words, the plurality of strands or strips may comprise a first population of strands or strips having a first aspect ratio and a second population of strands or strips having a second aspect ratio that is different to the first aspect ratio.

[0162] A first dimension, or cut width, of the strands or strips of aerosolisable material is between 0.9 mm and 1.5 mm. When strands or strips of aerosolisable material have a cut width of below 0.9 mm are incorporated into an article for use in a non-combustible aerosol provision system, the pressure drop across the article may be increased to a level that renders the article unsuitable for use in a non-combustible aerosol-provision device. However, if the strands or strips have a cut width above 2 mm (e.g. greater than 2 mm), then it may be challenging to insert the strands or strips of aerosolisable material into the article during its manufacture. In a preferred embodiment, the cut width of the strands or strips of aerosolisable material is between about 1 mm and 1.5 mm.

[0163] The consumable as defined herein could be incorporated into these materials by spraying onto the sheet / shreds / strands or they could be incorporated into the slurry during their manufacture (not for leaf, though, which comes from the field and is processed, shredded and blended.Carrier

[0164] When the formulation is in the form of a solid, including in the form of the aerosolgenerating material described above, the formulation or material may be present on or in a carrier which acts as a support. The carrier may function as a support on which the aerosolgenerating material is formed, thereby easing manufacture. The carrier may also provide rigidity to the aerosol-generating material, easing handling.

[0165] The carrier may be any suitable material which can be used to support an aerosolgenerating material. In some cases, the carrier may be formed from materials selected from metal foil, paper, carbon paper, greaseproof paper, ceramic, carbon allotropes, such as graphite and graphene, plastic, cardboard, wood or combinations thereof. In some cases, the carrier may be formed from materials selected from metal foil, paper, cardboard, wood or combinations thereof. In some cases, the carrier comprises paper. In some cases, the carrier itself may be a laminate structure comprising layers of materials selected from the preceding lists. In some cases, the carrier may also function as a flavour support. For example, the carrier may be impregnated with a flavourant. The carrier may also function as a support for the consumable defined herein (which, as noted herein, may be considered a ‘flavour block’).Nicotine

[0166] As is understood by one skilled in the art, nicotine may exist in free base form, monoprotonated form or diprotonated form. The structures of each of these forms are given below.nicotine free base monoprotonated nicotine diprotonated nicotine

[0167] Reference in the specification to protonated form means both monoprotonated nicotine and diprotonated nicotine. Reference in the specification to amounts in the protonated formmeans the combined amount of monoprotonated nicotine and diprotonated nicotine.

[0168] For ease of reference, these and further aspects of the present invention are now discussed under appropriate section headings. However, the teachings under each section are not necessarily limited to each particular section.

[0169] The present invention provides a formulation that contains nicotine, wherein at least 5 wt% of the nicotine present in the formulation is in protonated form. In some aspects at least a portion of the formulation may be in contact with a container, package or cartridge, e.g. formed from polycarbonate or polypropylene, or with a permeable package. In some aspects the containers, packages and cartridges described herein may be suitable for an aerosol provision system.

[0170] The relevant amounts of nicotine which are present in the formulation in protonated form are specified herein. These amounts may be readily calculated by one skilled in the art. Nicotine, 3-(1-methylpyrrolidin-2-yl) pyridine, is a diprotic base with pKa of 3.12 for the pyridine ring and 8.02 for the pyrrolidine ring. It can exist in pH-dependent protonated (mono- and di-) and non-protonated forms which have different bioavailability.

[0171] The distribution of protonated and non-protonated nicotine will vary at various pH increments.

[0172] The fraction of non-protonated nicotine will be predominant at high pH levels whilst a decrease in the pH will see an increase of the fraction of protonated nicotine (mono- or didepending on the pH). If the relative fraction of protonated nicotine and the total amount of nicotine in the sample are known, the absolute amount of protonated nicotine can be calculated.

[0173] The relative fraction of protonated nicotine in formulation can be calculated by usingthe Henderson-Hasselbalch equation, which describes the pH as a derivation of the acid dissociation constant equation, and it is extensively employed in chemical and biological systems. Consider the following equilibrium:

[0174] The Henderson-Hasselbalch equation for this equilibrium is:pH - pKa 4- log

[0175] Where [B] is the amount of non-protonated nicotine (i.e. free base), [BH+] 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 fraction of protonated nicotine can be derived from the alpha value of the non-protonated nicotine calculated from the Henderson-Hasselbalch equation as:% protonated, nicotine = 100

[0176] Determination of pKa values of nicotine solutions may be was carried out using the basic approach described in “Spectroscopic investigations into the acid-base properties of nicotine at different temperatures”, Peter M. Clayton, Carl A. Vas, Tam T. T. Bui, Alex F. Drake and Kevin McAdam, .Anal. Methods, 2013,5, 81-88. This method is summarised below.

[0177] As will be understood by one skilled in the art, by polycarbonate it is meant a polymer containing the following repeating unit

[0178] In one aspect at least a portion of a container in contact with the formulation containing nicotine is formed from polycarbonate. In one aspect the majority of the container which is in contact with the formulation is formed from polycarbonate. In one aspect all the container which is in contact with the formulation is formed from polycarbonate. In one aspect the container is formed entirely from polycarbonate.

[0179] As will be understood by one skilled in the art, by polypropylene it is meant a polymer containing the following repeating unit>

[0180] In one aspect at least a portion of the container in contact with the formulation containing nicotine is formed from polypropylene. In one aspect the majority of the container which is in contact with the formulation is formed from polypropylene. In one aspect all the container which is in contact with the formulation is formed from polypropylene. In one aspect the container is formed entirely from polypropylene.

[0181] In one aspect the majority of the container which is in contact with the formulation containing nicotine is formed from polycarbonate, polypropylene or a combination thereof. In one aspect all the container which is in contact with the formulation containing nicotine is formed from polycarbonate, polypropylene or a combination thereof. In one aspect the container is formed entirely from polycarbonate, polypropylene or a combination thereof.

[0182] As discussed herein, the container of the present invention is typically provided for the delivery of formulation containing nicotine to or within an e-cigarette. The formulation containing nicotine may be held within an e-cigarette or may be sold as a separate container for subsequent use with or in an e-cigarette. As understood by one skilled in the art, e-cigarettes typically contain a unit known as a cartomiser which comprises a reservoir of the formulation, a wick material and a heating element for vaporising the nicotine. In one aspect the container is a cartomiser or is part of a cartomiser. In one aspect the container is not a cartomiser or part of a cartomiser and is a container, such as a tank, bottle or the like, which may be used to deliver the formulation to or within an e-cigarette.

[0183] In one aspect the container is part of an e-cigarette. Therefore in a further aspect the present invention provides an electronic vapour provision system comprising: a vaporiser for vaporising liquid for inhalation by a user of the electronic vapour provision system; a power supply comprising a cell or battery for supplying power to the vaporiser; a container in which is contained a formulation containing nicotine, wherein at least 5 wt% of the nicotine present in the formulation is in protonated form, and wherein at least a portion of the container in contact with the formulation containing nicotine is formed from polycarbonate or polypropylene.

[0184] As will be understood by one skilled in the art, contact may occur between the container and the formulation containing nicotine by any means. Provided the body of the container is contacted with formulation containing nicotine then the container and formulationare in contact. It is envisaged that the formulation could be 'free' in the sense that it is a liquid in direct contact with the walls of the container. In also envisaged, that the formulation may be held within a matrix (such as a foam) and the foam is in contact with the body of the container.

[0185] As discussed herein, we have found that by protonating at least a portion of the nicotine with the acetals, and specifically at least 5 wt.% of the nicotine present, loss of the nicotine during storage can be reduced. 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.

[0186] The nicotine protonation may be provided in such a manner to achieve the desired degree of protonation of nicotine. In one aspect the nicotine is protonated by an organic acid. In one aspect the nicotine is protonated by a carboxylic acid. The carboxylic acid may be any suitable carboxylic acid. In one aspect the nicotine is protonated by a mono-carboxylic acid.

[0187] In one aspect the nicotine is protonated by an acid selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, isobutyric acid, butyric acid, methylbutyric acid, 2-methylbutyric acid, 3-methylpentanoic acid, isovaleric acid, valeric acid, hexanoic acid, hepatanoic acid, octanoic acid, nonanoic acid, methylvaleric acid, decanoic acid, glycolic acid, 2-butenedioicacid (Z), 2-butenedioic acid (E), succinic acid,glyceric acid, malic acid, pyroglutamic acid, trihydroxybutanoic acid, tetrahydroxypentanoic acid, 2-keto-L-gluconic acid, quinic acid, gluconic acid, galactaric acid, hexadecanoic acid, caffeic acid, linoleic acid, linolenic acid, glucuronic acid, chlorogenic acid, fumaric acid, maleic acid, oxalic acid, oxaloacetic acid, acetoacetic acid, beta-hydroxybutyric acid, alphaketoglutaric acid, alpha-ketobutyric acid and mixtures thereof. In one aspect the nicotine is protonated by an acid selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, isobutyric acid, butyric acid, methylbutyric acid, 2-methylbutyric acid, 3-methylpentanoic acid, isovaleric acid, valeric acid, hexanoic acid, hepatanoic acid, octanoic acid, nonanoic acid, methylvaleric acid, decanoic acid and mixtures thereof.

[0188] In one aspect the nicotine is protonated by one or more keto acids. In one aspect the nicotine is protonated by a keto acid. In one aspect the nicotine is protonated by an acid selected from the group consisting of alpha-keto acids, beta-keto acids, gamma-keto acids and combinations thereof. In one aspect the nicotine is protonated by an acid selected from the group consisting of alpha-keto acids, gamma-keto acids and combinations thereof. In one aspect the nicotine is protonated by an acid selected from the group consisting of alpha-keto acids. In one aspect the nicotine is protonated by an acid selected from the group consisting of beta-keto acids. In one aspect the nicotine is protonated by an acid selected from the group consisting of gamma-keto acids.

[0189] In one aspect the nicotine is protonated by an acid selected from the group consisting of levulinic acid, pyruvic acid, oxaloacetic acid, acetoacetic acid, beta-hydroxybutyric acid, alpha-ketoglutaric acid, alpha-ketobutyric acid and combinations thereof.

[0190] In one aspect the nicotine is protonated by a mixture of acids comprising (i) one or more keto acids and (ii) one or more further acids selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, succinic acid, tartaric acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, isobutyric acid, butyric acid, methylbutyric acid, 2-methylbutyric acid, 3-methylpentanoic acid, isovaleric acid, valeric acid, hexanoic acid, hepatanoic acid, octanoic acid, nonanoic acid, methylvaleric acid, decanoic acid, glycolic acid, 2-butenedioic acid (Z), 2-butenedioic acid (E), succinic acid, glyceric acid, malic acid, pyroglutamic acid, trihydroxybutanoic acid, tetrahydroxypentanoic acid, 2-keto-L-gluconic acid, quinic acid, gluconic acid, galactaric acid, hexadecanoic acid, caffeic acid, linoleic acid, linolenic acid, glucuronic acid, chlorogenic acid, fumaric acid, maleic acid, oxalic acid, and mixtures thereof.

[0191] In one aspect the total amount of acid present in the formulation is at least 0.01 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.1 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.2 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.3 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.4 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.5 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.6 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 0.8 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 1.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is at least 1.2 mole equivalents based on the nicotine.

[0192] In one aspect the total amount of acid present in the formulation is of from 0.01 to 2.00 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.1 to 2.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.2 to 2.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.3 to 2.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.4 to 2.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.5 to 2.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.6 to 2.0 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.6 to 1.8 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.6 to 1.6 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.8 to 1.6 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 0.8 to 1.4 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 1.0 to 1.6 mole equivalents based on the nicotine. In one aspect the total amount of acid present in the formulation is of from 1.0 to 1.4 mole equivalents based on the nicotine.

[0193] In one aspect the nicotine is protonated by levulinic acid. In one aspect the nicotine is protonated by a mixture of levulinic acid and benzoic acid.

[0194] In one aspect levulinic acid is the only acid present.

[0195] In one aspect the amount of levulinic acid present in the formulation is at least 0.01 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.1 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.2 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.3 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.4 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.5 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.6 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 0.8 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 1.0 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is at least 1.2 mole equivalents based on the nicotine.

[0196] In one aspect the amount of levulinic acid present in the formulation is of from 0.01 to 2.00 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.01 to 1.80 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.01 to 1.60 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.01 to 1.40 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.1 to 1.4 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.2 to 1.4 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.2 to 1.2 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.3 to 1.2 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.3 to 1.0 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.3 to 0.8 mole equivalents based on the nicotine. In one aspect the amount of levulinic acid present in the formulation is of from 0.4 to 0.8 mole equivalents based on the nicotine.

[0197] In some embodiments the nicotine is protonated by the one or more acetals. In some embodiments the nicotine is protonated by the one or more acetals selected from acid substituted acyclic acetals, acid substituted cyclic acetals or combinations thereof. In some embodiments the nicotine is protonated by the one or more acetals selected from acid substituted acyclic acetals or acid substituted cyclic acetals. In some embodiments thenicotine is protonated by one or more acetals comprising acid substituted acyclic acetals. In some embodiments the nicotine is protonated by one or more acetals comprising acid substituted cyclic acetals. In some embodiments the nicotine is protonated by one or more acetals consisting essentially of acid substituted acyclic acetals. In some embodiments the nicotine is protonated by one or more acetals consisting essentially of acid substituted cyclic acetals. In some embodiments the nicotine is protonated by acid substituted acyclic acetals. In some embodiments the nicotine is protonated by acid substituted cyclic acetals.

[0198] . In some embodiments the nicotine is protonated by one or more acetals comprise compounds selected from acid substituted 1,3-dioxanes, 1,3-dioxolanes or mixtures thereof. In some embodiments the nicotine is protonated by one or more acetals are selected from acid substituted 1,3-dioxanes, 1,3-dioxolanes or mixtures thereof. In some embodiments the nicotine is protonated by one or more acetals are selected from acid substituted 1,3-dioxanes or 1,3-dioxolanes. In some embodiments the nicotine is protonated by one or more acetals comprise acid substituted 1,3-dioxanes. In some embodiments the nicotine is protonated by one or more acetals comprise acid substituted 1,3-dioxolanes. In some embodiments the nicotine is protonated by one or more acetals consist essentially of acid substituted 1,3-dioxanes. In some embodiments the nicotine is protonated by one or more acetals consist essentially of acid substituted 1,3-dioxolanes. In some embodiments the nicotine is protonated by one or more acetals are acid substituted 1,3-dioxanes. In some embodiments the nicotine is protonated by one or more acetals are acid substituted 1,3-dioxolanes.

[0199] In some embodiments the nicotine is protonated by compounds of Formula (II) as defined herein.

[0200] In some embodiments the nicotine is protonated by one or more acetals comprising, consisting essentially of, or consisting of 3-(5-hydroxy-2-methyl-1,3-dioxan-2-yl)propanoic acid, 3-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)propanoic acid and combinations thereof.

[0201] In some embodiments the nicotine is protonated by one or more acetals comprising, consisting essentially of, or consisting of 3-(5-hydroxy-2-methyl-1,3-dioxan-2-yl)propanoic acid.

[0202] In some embodiments the nicotine is protonated by one or more acetals comprising, consisting essentially of, or consisting of 3-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)propanoic acid.

[0203] In some embodiments the nicotine is protonated by a mixture of (i) one or more keto acids and (ii) one or more acetals. In some embodiments the nicotine is protonated by a mixture of (i) one or more keto acids and (ii) one or more acid substituted acetals. In some embodiments the nicotine is protonated by a mixture of (i) one or more keto acids and (ii) one or more acid substituted cyclic acetals. In some embodiments the nicotine is protonated by a mixture of (i) one or more keto acids and (ii) one or more acid substituted 1,3-dioxanes and / or acid substituted 1,3-dioxolanes. In some embodiments the nicotine is protonated by a mixture of (i) one or more keto acids and (ii) one or more acid substituted 1,3-dioxanes. In some embodiments the nicotine is protonated by a mixture of (i) one or more keto acids and (ii) one or more acid substituted acid substituted 1,3-dioxolanes. In some embodiments the nicotine is protonated by a mixture of (i) levulinic acid and (ii) one or more acid substituted 1 ,3-dioxanes and / or acid substituted 1,3-dioxolanes. In some embodiments the nicotine is protonated by a mixture of (i) levulinic acid and (ii) one or more acid substituted 1,3-dioxanes. In some embodiments the nicotine is protonated by a mixture of (i) levulinic acid and (ii) one or more acid substituted acid substituted 1 ,3-dioxolanes.

[0204] In some embodiments the one or more acetals are present in an amount of about 0.001 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.01 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.05 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.1 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.2 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.3 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.4 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 0.5 wt% to about 10 wt%, based on the total weight of the formulation. In some embodiments the one or more acetals are present in an amount of about 1 wt% to about 10 wt%, based on the total weight of the formulation.

[0205] In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 1000 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 500 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 100 ppm. In some embodiments the one or more acetals are present in the formulation in anamount of 1 ppm to about 80 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 60 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 40 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 30 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 20 ppm. In some embodiments the one or more acetals are present in the formulation in an amount of 1 ppm to about 10 ppm.

[0206] Nicotine may exist in free base form, monoprotonated form or diprotonated form.

[0207] In some embodiments, the formulation has a pH of less than about 8. In some embodiments, the formulation has a pH of less than about 7.5. In some embodiments, the formulation has a pH of less than about 7.4. In some embodiments, the formulation has a pH of less than about 7.3. In some embodiments, the formulation has a pH of less than about 7.2. In some embodiments, the formulation has a pH of less than about 7.1. In some embodiments, the formulation has a pH of less than about 7.0. In some embodiments, the formulation has a pH of less than about 6.5. In some embodiments, the formulation has a pH of from about 5.5 to 7.5. In some embodiments, the formulation has a pH of from about 5.5 to 7.4. In some embodiments, the formulation has a pH of from about 5.5 to 7.3. In some embodiments, the formulation has a pH of from about 5.5 to 7.2. In some embodiments, the formulation has a pH of from about 5.5 to 7.1. In some embodiments, the formulation has a pH of from about 5.5 to 7. In some embodiments, the formulation has a pH of from about 6 to 7.5. In some embodiments, the formulation has a pH of from about 6 to 7.4. In some embodiments, the formulation has a pH of from about 6 to 7.3. In some embodiments, the formulation has a pH of from about 6 to 7.2. In some embodiments, the formulation has a pH of from about 6 to 7.1. In some embodiments, the formulation has a pH of from about 6 to 7. In some embodiments, the formulation has a pH of from about 6.5 to 7. In some embodiments, the formulation has a pH of from about 6 to 6.5. In some embodiments, the formulation has a pH of about 6. In some embodiments, the formulation has a pH of about 6.5. In some embodiments, the formulation has a pH of about 7. In some embodiments, the formulation has a pH of about 7.5.

[0208] As discussed herein we have found that by protonating at least some of the nicotine present in a formulation, the stability of the formulation containing nicotine may be enhanced. We have found that consumables, formulations and substance delivery system comprising nicotine, when stored for significant periods, suffer loss of nicotine content. Although problems of stability are particularly observed when formulation containing nicotine is stored in contact with polycarbonate or polypropylene, the problems are not exclusive to those materials. The present invention therefore provides a novel process for stabilising a formulation containingnicotine. The present invention provides a process for stabilising a formulation containing nicotine, the process comprising the steps of protonating the nicotine present in the formulation such that at least 5 wt% of the nicotine present in the formulation is in protonated form.

[0209] In the process of the present invention the formulation containing nicotine may be in contact with polycarbonate or polypropylene.

[0210] We have found that extended periods of storage are possible with the practice of the present invention. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 7 days. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 14 days. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 21 days. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 28 days. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 2 months. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 3 months. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 4 months. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 5 months. In one aspect the process provides for storage of the formulation containing nicotine in contact with polycarbonate or polypropylene for a period of at least 6 months.

[0211] The present invention further provides a novel use for stabilising a formulation containing nicotine. In one aspect the present invention provides use of protonation of nicotine for stabilising a formulation containing nicotine. In one aspect the present invention provides use of protonation of nicotine for improving storage stability of a formulation containing nicotine. In one aspect the present invention provides use of protonation of nicotine for reducing evaporative loss of nicotine from a formulation containing nicotine.

[0212] In one aspect the present invention provides use of protonated nicotine for stabilising a formulation containing nicotine free base. In one aspect the present invention provides use of protonated nicotine for improving storage stability of a formulation containing nicotine free base. In one aspect the present invention provides use of protonated nicotine for reducingevaporative loss of nicotine from a nicotine free base formulation. It will be understood that by 'nicotine free base formulation' it may be meant a formulation containing nicotine free base and protonated nicotine in an amount as described herein.

[0213] In one aspect the present invention provides use of an acid for stabilising a formulation containing nicotine. In some embodiments both the acid and one or more acetals may stabilise the nicotine containing formulation. In one aspect the present invention provides use of an acid for improving storage stability of a formulation containing nicotine. In one aspect of use in accordance with the present invention the acid is an organic acid. In one aspect of use in accordance with the present invention the acid is a carboxylic acid. In one aspect of use in accordance with the present invention the acid is a mono-carboxylic acid. In one aspect of use in accordance with the present invention 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, oleic acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof. In one aspect of use in accordance with the present invention the acid is selected from the group consisting of benzoic acid, levulinic acid, and mixtures thereof. In one aspect of use in accordance with the present invention the acid is levulinic acid. In one aspect of use in accordance with the present invention the acid is benzoic acid. In one aspect of use in accordance with the present invention the acid is a mixture of levulinic acid and benzoic acid.

[0214] In one aspect the present invention provides use of acetals and / or acids, as defined herein, for stabilising a formulation containing nicotine. In one aspect the present invention provides use of acetals and / or acids for improving storage stability of a formulation containing nicotine. In one aspect the present invention provides use of acetals and / or acids for reducing evaporative loss of nicotine from a formulation containing nicotine. In one aspect the present invention provides use of acetals, as defined herein, for stabilising a formulation containing nicotine. In one aspect the present invention provides use of acetals for improving storage stability of a formulation containing nicotine. In one aspect the present invention provides use of acetals for reducing evaporative loss of nicotine from a formulation containing nicotine.

[0215] In the use aspects of the present invention at least 5 wt% of the nicotine present in the formulation containing nicotine may be in protonated form.

[0216] In one aspect the present invention provides use of protonation of nicotine for stabilising a formulation containing nicotine with respect to polycarbonate or polypropylene. In one aspect the present invention provides use of protonation of nicotine for improving storage stability of a formulation containing nicotine with respect to polycarbonate or polypropylene.

[0217] Nicotine may be provided in any suitable amount depending on the desired dosage when the formulation is aerosolised and inhaled by the user. In some embodiments nicotine is present in an amount of no greater than about 6 wt% based on the total weight of the formulation. In some embodiments nicotine is present in an amount of from about 0.1 to about 6 wt% based on the total weight of the formulation, such as from about 0.5 to about 6 wt% based on the total weight of the formulation, even about 0.5 to about 5 wt% based on the total weight of the formulation.

[0218] In some embodiments the aerosolisable formulation is a liquid and may comprise about 1% to about 25% by weight of the consumable, where the consumable is defined according to the embodiments above, about 50 to about 99 wt% of the carrier, and about 0.1 to about 6 wt% of nicotine. In some embodiments the aerosolisable formulation is a liquid and may comprise about 5% by weight to about 20% by weight of the consumable, where the consumable is defined according to the embodiments above, about 60 to about 98 wt% of the carrier, and about 0.5 to about 6 wt% of nicotine. In some embodiments the aerosolisable formulation is a liquid and may comprise about 10% by weight to about 15% by weight of the consumable, where the consumable is defined according to the embodiments above, about 70 to about 95 wt% of the carrier, and about 0.5 to about 5 wt% of nicotine.

[0219] In some embodiments the formulation may contain one or more acids in addition to nicotine (as the active agent). In some embodiments, the one or more acids may be one or more organic acids. In some embodiments, the one or more acids may be one or more organic acids selected from the group consisting of benzoic acid, levulinic acid, malic acid, maleic acid, fumaric acid, citric acid, lactic acid, acetic acid, succinic acid, and mixtures thereof. When included in the formulation in combination with nicotine, the one or more acids may provide a formulation in which the nicotine is at least partially in protonated (such as monoprotonated and / or diprotonated) form. In some embodiments the one or more acids comprises benzoic acid and / or levulinic acid. In some embodiments the one or more acids comprises benzoic acid.

[0220] In some embodiments the formulation may contain one or more further acids in addition to those defined above. In some embodiments, the one or more acids may be one or more fatty acids. In some embodiments, the one or more acids may be one or more saturated and / or unsaturated acids. In some embodiments, the one or more further acids may be one or more C3 to C18 saturated fatty acids and / or C3 to C18 unsaturated fatty acids.

[0221] In some embodiments, the one or more fatty acids may be selected from the group comprising of: decanoic acid; dodecanoic acid; tetradecanoic acid; n-hexadecanoic acid;palmitic acid; octadecanoic acid; stearic acid; propanoic acid; lactic acid; butanoic acid, 4-hydroxy-; butanoic acid, 2-methyl-; butanoic acid, 3-methyl-; isovaleric acid; valeric acid; tiglic acid; pentanoic acid, 4-oxo-; pentanoic acid, 3-methyl-; pentanoic acid, 4-methyl-; hexanoic acid, 2-methyl-; octanoicacid; pelargonic acid; pentadecanoic acid; linolenic acid; linoleic acid; 13-L-hydroperoxylinoleic acid; elaidic acid; fumaric acid; 2-butenoic acid, (E)-.

[0222] In some embodiments, the C3 to C18 saturated fatty acids may be selected from the group comprising of: decanoic acid; dodecanoic acid; tetradecanoic acid; n-hexadecanoic acid; palmitic acid; octadecanoic acid; stearic acid; propanoic acid; lactic acid; butanoic acid, 4-hydroxy-; butanoic acid, 2-methyl-; butanoic acid, 3-methyl-; isovaleric acid; valeric acid; tiglic acid; pentanoic acid, 4-oxo-; pentanoic acid, 3-methyl-; pentanoic acid, 4-methyl-; hexanoic acid, 2-methyl-; octanoic acid; pelargonic acid. In some examples, the C14 to C18 saturated fatty acids may be selected from the group comprising of: tetradecanoic acid; n-hexadecanoic acid; palmitic acid; octadecanoic acid; stearic acid.

[0223] In some embodiments, the C3 to C18 unsaturated fatty acids may be selected from the group comprising of: pentadecanoic acid; linolenic acid; linoleic acid; 13-L-hydroperoxylinoleic acid; elaidic acid; 2-butenoic acid, (E)-. In some examples, the C16 to C20 unsaturated fatty acids may be selected from the group comprising of: linolenic acid; linoleic acid; 13-L-hydroperoxylinoleic acid; elaidic acid.

[0224] In some embodiments, the formulation further comprises a combination of fatty acids consisting of three C3 to C18 saturated fatty acids and at least one C3 to C18 unsaturated fatty acid. In some examples, the formulation further comprises a combination of fatty acids consisting of three C3 to C18 unsaturated fatty acids and nine C3 to C18 saturated fatty acids.

[0225] In some embodiments, the formulation further comprises no more than four unsaturated fatty acids.

[0226] In some embodiments, the formulation further comprises a combination of fatty acids consisting of butanoic acid, 2-methyl-; palmitic acid; 3-methylvaleric acid; and linolenic acid.

[0227] In some embodiments, the formulation further comprises a combination of fatty acids consisting of butanoic acid, 2-methyl-; palmitic acid, valeric acid and linolenic acid.

[0228] In some embodiments, the formulation further comprises a combination of fatty acids consisting of butanoic acid, 2-methyl-; palmitic acid and 3-methylvaleric acid.

[0229] In some embodiments, the formulation further comprises a combination of fatty acids consisting of palmitic acid and linolenic acid.

[0230] In some embodiments, the formulation further comprises a combination of fatty acids consisting of valeric acid, linolenic acid, palmitic acid and 3-methylvaleric acid.

[0231] In some embodiments, the formulation further comprises a combination of fatty acids consisting of butanoic acid, 2-methyl-; valeric acid; linolenic acid; palmitic acid; pentadecanoic acid; stearic acid; tetradecanoic acid; butanoic acid, 4-hydroxy-; lactic acid; n-hexadecanoic acid; octadecanoic acid; and elaidic acid.

[0232] In some embodiments, the formulation further comprises a combination of fatty acids consisting of butanoic acid, 2-methyl-; 3-methylvaleric acid; linolenic acid; palmitic acid; pelargonic acid; pentadecanoic acid; tetradecanoic acid; butanoic acid, 4-hydroxy-; lactic acid; n-hexadecanoic acid; octadecanoic acid; and elaidic acid.

[0233] In some embodiments, the weight ratio of the unsaturated fatty acids to the saturated fatty acids, if both present in the combination of fatty acids, is of from about 2.0:1.0 to about 1.0:2.5. In some examples, the weight ratio of the unsaturated fatty acids to the saturated fatty acids, if both present in the combination of fatty acids, is of from about 1.0: 1.0 to about 1.0:2.2. In some examples, the weight ratio of the unsaturated fatty acids to the saturated fatty acids, if both present in the combination of fatty acids, is of from about 1.0: 1.7 to about 1.0 to 2.2.Binder

[0234] In some embodiments there is provided an aerosolisable formulation comprising the consumable as defined herein, one or more binders, and optionally a botanical material. In some embodiments, the binder consists of one or more gelling agent(s). Suitably, the aerosolisable formulation comprises from about 2 wt% to about 80 wt% binder(s), for example from about 5 wt%, 7 wt%, 10 wt%, 15 wt%, 17 wt%, 20 wt%, or 25 wt% to about 70 wt%, 60 wt%, 50 wt%, 45 wt%, 40 wt%, 35 wt% or 30 wt% of one or more binders (all calculated on a dry weight basis). For example, the aerosolisable formulation may comprise about 5-70 wt%, 7-60 wt%, 10-50 wt%, 15-45 wt%, 17-40 wt%, 20-35 wt% or 25-30 wt% of the binder(s).

[0235] In some embodiments, the one or more binders comprises one or more gelling agent(s). In some embodiments, the one or more binders consist of one or more gelling agent(s). In some embodiments, the gelling agent comprises a hydrocolloid.

[0236] In some embodiments, the one or more binders comprises (or is) one or more compounds selected from polysaccharide gelling agents, such as alginate, pectin, starch or a derivative thereof, cellulose or a derivative thereof, pullulan, carrageenan, agar and agarose;gelatin; gums, such as xanthan gum, guar gum and acacia gum; silica or silicone compounds, such as PDMS and sodium silicate; clays, such as kaolin; and polyvinyl alcohol.

[0237] In some embodiments the one or more binders comprises (or is) one or more polysaccharide gelling agents. In some embodiments, the polysaccharide gelling agent is selected from alginate, pectin, starch or a derivative thereof, or cellulose or a derivative thereof. In some embodiments the polysaccharide gelling agent is selected from alginate and a cellulose derivative.

[0238] In some embodiments, the one or more binders is a polysaccharide gelling agent, optionally wherein the polysaccharide gelling agent is selected from alginate and a cellulose derivative. In some embodiments, the polysaccharide gelling agent is alginate. In some embodiments, the alginate is sodium alginate.

[0239] In some embodiments, the polysaccharide gelling agent is a cellulose derivative. Without wishing to be bound by theory, it is believed that such gelling agents do not react with calcium ions to form crosslinks. In some embodiments the binder is not cross-linked. The absence of crosslinks in the gelling agent may facilitate quicker delivery of the consumable (and any optional additional active substances and / or flavours) from the aerosolisable formulation.

[0240] Examples of cellulosic binders (also referred to herein as cellulosic gelling agents or cellulose derivatives) include, but are not limited to, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), methyl cellulose, ethyl cellulose, cellulose acetate (CA), cellulose acetate butyrate (CAB), and cellulose acetate propionate (CAP). In some embodiments the cellulose or derivative thereof is selected from hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), methyl cellulose, ethyl cellulose, cellulose acetate (CA), cellulose acetate butyrate (CAB), and cellulose acetate propionate (CAP). In some embodiments, the cellulose derivative is CMC. For example, in some embodiments, the binder comprises (or is) one or more of alginate, pectin, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethylcellulose, pullulan, xanthan gum, guar gum, carrageenan, agarose, acacia gum, fumed silica, PDMS, sodium silicate, kaolin and polyvinyl alcohol.

[0241] In some embodiments, the binder comprises (or is) one or more of hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethylcellulose, guar gum, acacia gum, alginate and / or pectin.

[0242] In some cases, the binder comprises (or is) alginate and / or pectin, and may be combined with a setting agent (such as a calcium source) during formation of the aerosolisable formulation. In some cases, the binder may comprise a calcium-cross-linked alginate and / or a calcium-cross-linked pectin.

[0243] In some embodiments, the binder comprises (or is) alginate, optionally wherein the alginate is present in the aerosolisable formulation in an amount of from about 5-70 wt%, 7-60 wt%, 10-50 wt%, or 15-45 wt%, of the aerosolisable formulation (calculated on a dry weight basis).

[0244] In some embodiments, alginate is the only binder present in the aerosolisable formulation. In other embodiments, the binder comprises alginate and at least one further binder, such as pectin. In particular embodiments, the binder is carboxymethylcellulose, optionally wherein the carboxymethylcellulose (CMC) is present in an amount of about 2-80 wt%, for example about 5-70 wt%, 10-60 wt%, 15-50 wt%, 17-45 wt%, 20-40 wt% or about 30 wt%. In some embodiments, CMC is the only binder present in the aerosolisable formulation.

[0245] The aerosolisable formulation with one or more binders may be in the form of aerosolgenerating material as defined above. In some embodiments the aerosol-generating material may comprise one or more binders and an aerosol former material. The aerosol former material may be as defined above and may be present in an amount of from about 1wt%, 5wt%, 10wt%, 12wt% or 13wt% to about 18wt%, 20wt%, 25wt%, 30wt%, 35wt%, 45wt%, 55wt%, 65wt%, 15 75wt% or 80wt% of an aerosol former material (all calculated on a dry weight basis). In exemplary embodiments, the aerosol-generating material comprises from about 1 to about 80 wt%, from about 1 to about 50 wt%, from about 5 to about 35 wt%, from about 10 to about 25 wt%, from about 12 to about 20 wt% or from about 13 to about 18 wt% of an aerosol former material (all calculated on a dry weight basis).

[0246] In some embodiments, the aerosol former material may, in addition to the polyhydric alcohol (e.g. glycerol) contained within the consumable, comprise one or more further constituents capable of forming an aerosol. In some embodiments, the aerosol former material may further comprise one or more compounds selected from diols, triols, tetrols and combinations thereof. In some embodiments, the aerosol former material may further comprise one or more compounds selected from diols. In some embodiments, the aerosol former material may further comprise one or more compounds selected from triols. In some embodiments, the aerosol former material may further comprise one or more compounds selected from tetrols.

[0247] In some embodiments, the aerosol former material may further comprise one or more compounds selected from monosaccharides, disaccharides, polysaccharides, esters, diesters, fatty acid esters, glycol esters, citric acid esters, sugar alcohol esters, choline derivatives, aprotic imidazoliums, diols, sugar alcohols, straight-chain alkanes, polysorbates, polyethers and combinations thereof.

[0248] In some embodiments, the aerosol former material may further comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, propylene carbonate, maltitol, propylene glycol caprylate, diisoamyl adipate, ethyl octanoate, “L-Lysine, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium (1:1)”, cholin acetate, 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium acetate, 1-ethyl-3-methylimidazolium propionate, 1-ethyl-3-methylimidazolium octanoate, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1,3-butanediol, isopropyl myristate, 2,3-butanediol, D-mannitol, hexadecane, 1,3-propanediol, decyl glucoside, triethylene glycol bis(2-ethyl hexanoate), Bis(2-ethylhexyl) adipate, acetyl triethyl citrate, acetyl trihexyl citrate, acetyl trioctyl citrate, triethyl 2-(1 ,2-dioxopropoxy)propane-1 ,2,3-tricarboxylate, “methacrylic acid;triethyl-2-hydroxypropane-1 ,2,3-tricarboxylate”, “sodium;triethyl-2-hydroxypropane-1 ,2,3-tricarboxylate, “but-3-enoic acid;acetyl tributyl citrate”, acetyl triethyl citrate, bis(2-ethylhexyl) adipate, polyoxyethylene (20) sorbitan monooleate, isopropyl palmitate, sorbitan trioleate, sorbitan monolaurate, sorbitan tristearate, isopropyl isostearate, and polyethylene glycol 600.

[0249] In some embodiments, the aerosol former material may further comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, meso-erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid and propylene carbonate. In some embodiments, the aerosol former material may further comprise propylene glycol. In some cases, the aerosol former material comprises, consists essentially of or consists of glycerol, ora mixture of glycerol and propylene glycol.

[0250] In some embodiments, the aerosol former material may comprise one or more of maltitol, propylene glycol, caprylate, “L-Lysine, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium (1:1)”, cholin acetate, 1,3-butanediol, 2-methyl-1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 3-methyl-1,3-butanediol, 2,3-butanediol, 1,3-propanediol, triethyl citrate, decyl glucoside, triethylene glycol bis(2-ethylhexanoate), acetyl trihexyl citrate,sorbitan monooleate, sorbitan trioleate, sorbitan monolaurate, sorbitan tristearate, and polyethylene glycol 600.

[0251] In some embodiments, the aerosol former material comprises one or more polyhydric alcohols, such as propylene glycol, triethylene glycol, 1,3-butanediol and glycerine esters of polyhydric alcohols, such as glycerol mono-, di- or triacetate; and / or aliphatic esters of mono, di- or polycarboxylic acids, such as dimethyl dodecanedioate and dimethyl tetradecanedioate In some embodiments the aerosol former material may comprise glycerol and / or propylene glycol.Filler

[0252] The aerosolisable formulation may further comprise a filler. Use of a filler may help to reduce tackiness of the aerosolisable formulation, for example if high levels of aerosol former material are present. Suitably, the aerosolisable formulation comprises from about 2 wt% to about 60 wt% binder and any optional filler.

[0253] In some embodiments, filler is present in an amount of less than about 50 wt% of a filler, such as from about 1 wt% to 50 wt%, or 5 wt% to 40 wt%, or 5 wt% to 30 wt%, or 10 wt% to 20 wt%. In other embodiments, filler is present in an amount of less than 20 wt%, suitably less than 10 wt% or less than 5 wt%. In some cases, the aerosolisable formulation comprises less than 1 wt% of a filler, and in some cases, comprises no filler.

[0254] The filler, if present, may comprise one or more inorganic filler materials, such as calcium carbonate, perlite, vermiculite, diatomaceous earth, colloidal silica, magnesium oxide, magnesium sulphate, magnesium carbonate, and suitable inorganic sorbents, such as molecular sieves. The filler may comprise one or more organic filler materials such as wood pulp; tobacco pulp; hemp fibre; starch and starch derivatives, such as maltodextrin; chitosan; and cellulose and cellulose derivatives, such as ground cellulose, microcrystalline cellulose and nanocrystalline cellulose. In particular cases, the aerosolisable formulation comprises no calcium carbonate such as chalk.

[0255] In particular embodiments which include filler, the filler is fibrous. For example, the filler may be a fibrous organic filler material such as wood pulp, tobacco pulp, hemp fibre, cellulose or cellulose derivatives. In some embodiments, the fibrous organic filler material may be wood pulp, hemp fibre, cellulose or cellulose derivatives. In some embodiments, the fibrous filler is wood pulp. Without wishing to be bound by theory, it is believed that including fibrous filler in an aerosolisable formulation may increase the tensile strength of the material. This may be particularly advantageous in examples wherein the aerosolisable formulation isprovided as a sheet, such as when a sheet circumscribes a rod of aerosolisable or aerosol generating material.Botanical material

[0256] In some embodiments the aerosolisable formulation includes a botanical material. As used herein, the term "botanical" includes any material derived from plants including, but not limited to, extracts, leaves, bark, fibres, 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.

[0257] Example botanicals are tobacco, 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, Memtha longifolia, Mentha suaveolens variegata, Mentha pulegium, Mentha spicata c.v. and Mentha suaveolens.

[0258] In some embodiments, the botanical is tobacco. In some embodiments, the botanical is selected from eucalyptus, star anise, cocoa and hemp. In some embodiments, the botanical is selected from rooibos and fennel.Further Constituents

[0259] The formulation may comprise one or more further constituents. In particular, one or more further constituents may be selected from one or more active agents, and / or one or more functional constituents. In some embodiments, the active agent is a physiologically active agent and may be selected from nicotine, nicotine salts (e.g. nicotine ditartrate / nicotine bitartrate), nicotine-free tobacco substitutes, other alkaloids such as caffeine, or mixtures thereof. In other embodiments, the formulation is nicotine-free meaning that no nicotine is included in the formulation.

[0260] By "active agent" it is meant an agent which has a biological effect, such as sensorial and / or physiological effect, on a subject when the aerosol is inhaled. In one aspect by "active agent" it is meant an agent which has a physiological effect on a subject when the aerosol is inhaled. In some cases, the active may be a flavour. The active agent may also be selected from nutraceuticals, nootropics, psychoactives and sensates. In some embodiments, the active agent is selected from nutraceuticals, nootropics and psychoactives. The active substance may be naturally occurring or synthetically obtained. The active agent may comprise for example nicotine, caffeine, taurine, theine, vitamins such as B6 or B12 or C, melatonin, cannabinoids, or constituents, derivatives, or combinations thereof. The active agent may comprise one or more constituents, derivatives or extracts of tobacco, cannabis or another botanical. In some embodiments, the active agent comprises caffeine, melatonin or vitamin B12. The one or more active agents may be selected from nicotine, botanicals, and mixtures thereof. The one or more active agents may be of synthetic or natural origin. The active could be an extract from a botanical, such as from a plant in the tobacco family as discussed above. In one aspect the active agent is at least nicotine. In one aspect the active agent consists of nicotine and / or salts thereof as discussed above.

[0261] As noted herein, the active agent may comprise one or more constituents, derivatives or extracts of cannabis, such as one or more cannabinoids or terpenes. Cannabinoids are a class of natural or synthetic chemical compounds that act on cannabinoid receptors (i.e. , CB1 and CB2) in cells that repress neurotransmitter release in the brain. Cannabinoids are cyclic molecules exhibiting particular properties such as the ability to cross the blood-brain barrier with ease. Cannabinoids may be naturally occurring (phytocannabinoids) from plants such as cannabis, (endocannabinoids) from animals, or artificially manufactured (synthetic cannabinoids). Cannabis species express at least 85 different phytocannabinoids, and these may be divided into subclasses, including cannabigerols, cannabichromenes, cannabidiols, tetrahydrocannabinols, cannabinols and cannabinodiols, and other cannabinoids, such as cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), including its isomers A6a,10a-tetrahydrocannabinol (A6a,10a-THC), A6a(7)-tetrahydrocannabinol (A6a(7)-THC), A8-tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A9-THC), A10-tetrahydrocannabinol (A10-THC), A9,11-tetrahydrocannabinol (A9.11-THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), Cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A).

[0262] Although the legal status of specific cannabinoids varies from jurisdiction to jurisdiction, certain active components, for example cannabidiol (CBD), tetrahydrocannabinol (THC) and cannabinol (CBN), are being considered for use in a wide variety of applications, such as in formulations for use in aerosol delivery systems. However, the stability of cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC) and cannabinol (CBN), has been found to vary depending on certain environmental conditions, such as exposure to air or light, or variation in temperature and pH. This may have unintended and detrimental consequences.

[0263] For example, CBD may oxidise and degrade when exposed to light and / or air to form cannabidiol hydroxyquinone (CBDHQ or HU-331) and its isomeric or functional derivatives. Furthermore, CBD may be converted to A9-tetrahydrocannabinol (A9-THC) in response to variations in temperature and / or pH. As a result, the accuracy of the specified cannabinoid content and / or concentration may vary widely in the formulations, while regulated and restricted cannabinoids may be produced unintentionally that will render the product as illicit or unlicensed in certain jurisdictions. As such, there is a desire to provide formulations comprising one or more cannabinoids that maintain a high degree of purity during manufacture and storage, and in turn prevent the loss or degradation of one or more cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC) or cannabinol (CBN), in a formulation.

[0264] In some embodiments, the cannabinoid is a synthetic cannabinoid. In some embodiments, the cannabinoid is added to the material in the form of an isolate. An isolate is an extract from a plant, such as a cannabis plant. The cannabinoid(s) of interest are typically present in a high degree of purity, for example greater than 95%, greater than 96%, greater than 97%, greater than 98%, or around 99% purity. A synthetic cannabinoid is one which has been derived from a chemical synthesis as opposed to being isolated from a plant or biological source.

[0265] In some embodiments the cannabinoid(s) of interest are selected from cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), including its isomers A6a,10a-tetrahydrocannabinol (A6a,10a-THC), A6a(7)-tetrahydrocannabinol (A6a(7)-THC), A8-tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A9-THC), A10-tetrahydrocannabinol (A10-THC), A9, 11 -tetrahydrocannabinol (A9,11-THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). In some embodiments the cannabinoid(s) of interest are selected from cannabigerol (CBG),cannabichromene (CBC), cannabidiol (CBD), A8-tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A9-THC) and cannabinol (CBN).

[0266] In some embodiments the cannabinoid(s) of interest are selected from cannabidiol (CBD), A8-tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A9-THC). In some embodiments the cannabinoid of interest is cannabidiol (CBD). In some embodiments the cannabinoid of interest is A8-tetrahydrocannabinol (A8-THC). In some embodiments the cannabinoid of interest is A9-tetrahydrocannabinol (A9-THC). In some embodiments the cannabinoid of interest is cannabinol (CBN).

[0267] As noted herein, the active agent may comprise or be derived from one or more botanicals or constituents, derivatives or extracts thereof. In some embodiments, the active agent comprises or is derived from one or more botanicals or constituents, derivatives or extracts thereof and the botanical is tobacco. In some embodiments, the active agent comprises or is 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 some embodiments, the 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.

[0268] When nicotine is present in the formulation, it may be present in protonated and / or unprotonated form. In some embodiments, the formulation comprises nicotine in unprotonated form and nicotine in monoprotonated form. It may also be that small amounts of diprotonated nicotine are present. In one aspect the formulation comprises nicotine in unprotonated form, nicotine in monoprotonated form and nicotine in diprotonated form.

[0269] As discussed herein the formulation may additionally comprise nicotine in unprotonated form and nicotine in protonated form. As will be understood by one skilled in the art, the protonated form of nicotine may be prepared by reacting unprotonated nicotine with acetals and / or acids, as defined herein.

[0270] In alternative embodiments, the aerosolisable formulation may be free of organic or inorganic acids and their corresponding salts. For example, the aerosolisable formulation may be free of carboxylic acids and free of phosphoric acids.

[0271] Where present, the amount of organic acid present may vary. The formulation may comprise from about 0.01% to about 10% by weight of organic acid, present as one or more organic acids, based on the total weight of the formulation. In some embodiments, the formulation comprises at least about 0.01%, at least about 0.1 %, about 0.2%, about 0.3%,about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or at least about 10% organic acid by weight, based on the total weight of the formulation. In some preferred embodiments, the formulation comprises from about 0.01% to about 5% by weight of organic acid. For example, the formulation comprises an organic acid in an amount of from about 0.1% to about 2.5% by weight of the formulation. In the case where a salt of an organic acid is added (e.g., citric acid anhydrate), the percent by weight is calculated based on the weight of the free acid, not including any counter-ion which may be present.

[0272] In some embodiments, the further constituent is selected from a "flavour" and / or "flavourant" which, where local regulations permit, may be used to create a desired taste or aroma in a product for adult consumers. It will be recognized by the person skilled in the art that a flavour or flavourant, in the context of the present disclosure, is not a sensate compound as defined herein. In some instances flavours or flavourants may include one or more of extracts (e.g., liquorice, hydrangea, Japanese white bark magnolia leaf, chamomile, fenugreek, clove, Japanese mint, aniseed, cinnamon, herb, Wintergreen, cherry, berry, peach, apple, Drambuie, bourbon, scotch, whiskey, spearmint, peppermint, lavender, cardamom, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, cassia, caraway, cognac, jasmine, ylang-ylang, sage, fennel, pimento, anise, coriander, coffee, and other additives such as charcoal, chlorophyll, minerals, or botanicals. They may be imitation, synthetic or natural ingredients or blends thereof. They may be in any suitable form, for example, oil, liquid, or powder.

[0273] The flavour may be added to the formulation as part of a so-called “flavour block”, where one or more flavours are blended together and then added to the aerosolisable material. The “flavour block” may be in addition to the consumable defined above, which may itself be a “flavour block”.

[0274] Where present, a flavouring agent may be included in the formulation in an amount up to about 10% by weight, such as up to about 5% by weight, such as up to about 1% by weight of the formulation. In some embodiments, a flavouring agent is present in an amount of from about 0.01% to about 5% by weight, preferably in an amount of from about 0.1% to about 2.5% by weight of the formulation, and more preferably in an amount of from about 0.25% to about 1 % by weight of the formulation.

[0275] The one or more other functional constituents may comprise one or more of colouring agents, preservatives, binders and / or fillers. Fillers, for example, may fulfil multiple functions, such as enhancing certain organoleptic properties such as texture and mouthfeel, enhancingcohesiveness or compressibility of the product, and the like. More details are set out above. A binder (or combination of binders) may be employed in the product in certain embodiments, in amounts sufficient to provide the desired physical attributes and physical integrity to the product. More details are set out above. A colouring agent may be employed in amounts sufficient to provide the desired physical attributes to the product.

[0276] In some embodiments, the aerosolisable material comprises less than 12%w / w water. In some embodiments, the aerosolisable material comprises less than 11%w / w water. In some embodiments, the aerosolisable material comprises less than 10%w / w water. In some embodiments, the aerosolisable material comprises less than 5%w / w water. In some embodiments, the aerosolisable material comprises less than 1%w / w water. In some embodiments, the aerosolisable material comprises less than 0.5%w / w water. In some embodiments, the aerosolisable material comprises substantially no water.

[0277] Such embodiments may also be defined with the concentration of consumable, carrier, and / or nicotine according to the embodiments above. It will be appreciated that such features are not repeated here for conciseness.

[0278] As the aerosolisable formulation embodiments include the consumable as defined herein, it will be appreciated that the components of the consumable are as defined above. This definition is not repeated here for conciseness but is equally applicable to the description of the aerosolisable formulation.SUBSTANCE DELIVERY SYSTEM

[0279] The present disclosure provides a substance delivery system comprising the consumable, formulation or article (e.g. container or package) defined herein. The substance delivery system can be implemented as a combustible aerosol provision system, a noncombustible aerosol provision system or an aerosol-free delivery system.

[0280] The non-combustible aerosol provision system is discussed further below. Combustible aerosol provision systems include cigarettes, cigarillos, cigars, and tobacco for pipes or for roll-your-own or for make-your-own cigarettes (whether based on tobacco, tobacco derivatives, expanded tobacco, reconstituted tobacco, tobacco substitutes or other smokeable material); and aerosol-free delivery systems are those that deliver the at least one substance to a user orally, nasally, transdermally or in another way without forming an aerosol, including but not limited to, lozenges, gums, patches, articles comprising inhalable powders, vapour provision systems that provide vapour as opposed to aerosol, and oral products such as oraltobacco which includes snus or moist snuff, wherein the at least one substance may or may not comprise nicotine.ARTICLE, AEROSOL PROVISION SYSTEM AND CONTAINER

[0281] In a further aspect there is provided an article comprising the formulation, e.g. an aerosolisable or vaporisable formulation, as defined herein. The article may be a container, such as a bottle, or may be a component for use with an aerosol or vapour provision device, such as a cartridge. For example, the article may comprise an area (store) for receiving the aerosolisable or vaporisable formulation defined herein, an aerosol or vapour generating component, an aerosol or vapour generating area, and optionally a mouthpiece.

[0282] In some embodiments, there is provided an article for use with an aerosol or vapour provision system, the article comprising a store comprising an aerosolisable or vaporisable formulation as defined herein, an aerosol or vapour generating component (such as, but not limited to, a heater), an aerosol or vapour generating area, a transport element, and a mouthpiece. Aerosolisable or vaporisable material (aerosolisable or vaporisable formulation) may be transferred from the store for receiving an aerosolisable or vaporisable material to the aerosol or vapour generating component via a transport element, such as a wick, pump or the like. The skilled person is able to select suitable transport elements depending on the type of aerosolisable or vaporisable material that is to be transported and the rate at which it must be supplied. Particular mention may be made of transport elements, such as wicks, formed from fibrous materials, foamed materials, sintered materials, woven and non-woven materials.

[0283] An airflow pathway typically extends through the article (optionally via the device) to an outlet. The pathway is oriented such that generated aerosol or vapour is entrained in the airflow such that it can be delivered to the outlet for inhalation by a user.

[0284] In some embodiments, the aerosol generating component is a heater.

[0285] Typically, the area for receiving an aerosolisable or vaporisable material will allow for the article to be refilled with aerosolisable or vaporisable material as the aerosolisable or vaporisable material is depleted during use.

[0286] In a further aspect there is provided an aerosol provision system comprising an aerosol provision device and an article as defined herein. The aerosol provision system is preferably non-combustible. A non-combustible aerosol provision system is a system that releases compounds from an aerosol-generating material without combusting the aerosol-generating material, such as electronic cigarettes, tobacco heating products, and hybrid systems togenerate aerosol using a combination of aerosol-generating materials. According to the present disclosure, a “non-combustible” aerosol provision system is one where a constituent aerosol-generating material of the aerosol provision system (or component thereof) is not combusted or burned in order to facilitate delivery of at least one substance to a user. The system may heat an aerosol-generating material or formulation or consumable thereof to a temperature of at least about 200°C. In some embodiments the aerosol provision system generates aerosol by heating to a temperature of about 250°C to about 400°C.

[0287] The aerosol provision system may also be referenced herein as an aerosol delivery system. In some embodiments, the delivery system is a non-combustible aerosol provision system, such as a powered non-combustible aerosol provision system. In some embodiments, the non-combustible aerosol provision system is an electronic cigarette, also known as a vaping device or electronic nicotine delivery system (END), although it is noted that the presence of nicotine in the aerosol-generating material is not a requirement.

[0288] In some embodiments, the non-combustible aerosol provision system is an aerosolgenerating material heating system, also known as a heat-not-burn system. An example of such a system is a tobacco heating system.

[0289] In some embodiments, the non-combustible aerosol provision system is a hybrid system to generate aerosol using a combination of aerosol-generating materials, one or a plurality of which may be heated. Each of the aerosol-generating materials may be, for example, in the form of a solid, liquid or gel and may or may not contain nicotine. In some embodiments, the hybrid system comprises a liquid or gel aerosol-generating material and a solid aerosol-generating material. The solid aerosol-generating material may comprise, for example, tobacco or a non-tobacco product.

[0290] Typically, the non-combustible aerosol provision system may comprise a non-combustible aerosol provision device and a consumable for use with the non-combustible aerosol provision device. The consumable being as defined herein.

[0291] In some embodiments, the non-combustible aerosol provision system, such as a non-combustible aerosol provision device thereof, may comprise a power source and a controller. The power source may, for example, be an electric power source or an exothermic power source. In some embodiments, the exothermic power source comprises a carbon substrate which may be energised so as to distribute power in the form of heat to an aerosol-generating material or to a heat transfer material in proximity to the exothermic power source.

[0292] Figure 1 is a highly schematic diagram (not to scale) of an example aerosol provision system, such as an e-cigarette 10, to which embodiments are applicable although not limited. The e-cigarette has a generally cylindrical shape, extending along a longitudinal axis indicated by a dashed line (although aspects of the invention are applicable to e-cigarettes configured in other shapes and arrangements), and comprises two main components, namely an aerosol provision device 20 and an article 30.

[0293] The article 30 includes a store for aerosolisable material (source liquid) 38 containing an aerosolisable material (source liquid) from which an aerosol is to be generated. The article 30 further comprises an aerosol generating component (heating element or heater) 36 for heating aerosolisable material to generate the aerosol. A transport element or wicking element or wick 37 is provided to deliver aerosolisable material from the store 38 to the heating element 36. A part or parts of the wick 37 are in fluid communication with aerosolisable material in the store 38 and by a wicking or capillary action aerosolisable material is drawn along or through the wick 37 to a part or parts of the wick 37 which are in contact with the heater 36.

[0294] Vaporization of the aerosolisable material occurs at the interface between the wick 37 and the heater 36 by the provision of heat energy to the aerosolisable material to cause evaporation, thus generating the aerosol. The aerosolisable material, the wick 37 and the heater 36 may be collectively referred to as an aerosol or vapour source. The wick 37 and the heater 36 may be collectively referred to as a vaporizer or an atomiser 15. Typically, a single wick will be present, but it is envisaged that more than one wick could be present, for example, two, three, four or five wicks.

[0295] As described above, the wick may be formed a sintered material. The sintered material may comprise sintered ceramic, sintered metal fibers / powders, or a combination of the two. The (or at least one of / all of the) sintered wick(s) may have deposited thereon / embedded therein an electrically resistive heater. Such a heater may be formed from heat conducting alloys such as NiCr alloys. Alternatively, the sintered material may have such electrical properties such that when a current is passed there through, it is heated. Thus, the aerosol generating component and the wick may be considered to be integrated. In some embodiments, the aerosol generating component and the wick are formed from the same material and form a single component.

[0296] In some embodiments, the wick is formed from a sintered metal material and is generally in the form of a planar sheet. Thus, the wick element may have a substantially thin flat shape. For example, it may be considered as a sheet, layer, film, substrate or the like. By this it is meant that a thickness of the wick is less or very much less than at least one of thelength and the width of the wick. Thus, the wick thickness (its smallest dimension) is less or very much less than the longest dimension.

[0297] The wick may be made of a homogenous, granular, fibrous or flocculent sintered metal(s) so as to form said capillary structure. Wick elements can be made from a conductive material which is a nonwoven sintered porous web structure comprising metal fibres, such as fibres of stainless steel. For example, the stainless steel may be AISI (American Iron and Steel Institute) 316L (corresponding to European standard 1.4404). The material’s weight may be in the range of 100 - 300 g / m2.

[0298] Where the wick is generally planar, the thickness of the wick may be in the range of 75 - 250 pm. A typical fibre diameter may be about 12 pm, and a typical mean pore size (size of the voids between the fibres) may be about 32 pm. An example of a material of this type is Bekipor (RTM) ST porous metal fibre media manufactured by NV Bekaert SA, Belgium, being a range of porous nonwoven fibre matrix materials made by sintering stainless steel fibres.

[0299] Note also that while the material is described as planar, this refers to the relative dimensions of the sheet material and the wick (a thickness many times smaller than the length and / or width) but does not necessarily indicate flatness, in particular of the final wick made from the material. A wick may be flat but might alternatively be formed from sheet material into a non-flat shape such as curved, rippled, corrugated, ridged, formed into a tube or otherwise made concave and / or convex.

[0300] The wick element may have various properties. It is formed from a porous material to enable the required wicking or capillary effect for drawing source liquid through it from a store for aerosolisable material (where the wick meets the aerosolisable material at a store contact site) to the vaporisation interface. Porosity is typically provided by a plurality of interconnected or partially interconnected pores (holes or interstices) throughout the material, and open to the outer surface of the material. Any level of porosity may be employed depending on the material, the size of the pores and the required rate of wicking. For example, a porosity of between 30% and 85% might be selected, such as between 40% and 70%, between 50% and 80%, between 35% and 75% or between 40% and 75%. This might be an average porosity value for the whole wick element, since porosity may or may not be uniform across the wick. For example, pore size at the store contact site might be different from pore size nearer to the heater.

[0301] It is useful for the wick to have sufficient rigidity to support itself in a required within the article. For example, it may be mounted at or near one or two edges and be required tomaintain its position substantially without flexing, bending or sagging. As an example, porous sintered ceramic is a useful material to use as the wick element. Any ceramic with appropriate porosity may be used. If porous ceramic is chosen as the porous wick material, this is available as a powder which can be formed into a solid by sintering (heating to cause coalescence, possibly under applied pressure). Sintering then solidifies the ceramic to create the porous wick.

[0302] The article 30 further includes a mouthpiece 35 having an opening through which a user may inhale the aerosol generated by the vaporizer 15. The aerosol for inhalation may be described as an aerosol stream or inhalable airstream.

[0303] The aerosol delivery device 20 includes a power source (a re-chargeable cell or battery 14, referred to herein after as a battery) to provide power for the e-cigarette 10, and a controller (printed circuit board (PCB)) 28 and / or other electronics for generally controlling the e-cigarette 10. The aerosol delivery device can therefore also be considered as a battery section, or a control unit or section.

[0304] During operation of the device, the controller will determine that a user has initiated a request for the generation of an aerosol. This could be done via a button on the device which sends a signal to the controller that the aerosol generator should be powered. Alternatively, a sensor located in or proximal to the airflow pathway could detect airflow through the airflow pathway and convey this detection to the controller. A sensor may also be present in addition to the presence of a button, as the sensor may be used to determine certain usage characteristics, such as airflow, timing of aerosol generation etc.

[0305] For example, in use, when the heater 36 receives power from the battery 14, as controlled by the circuit board 28 possibly in response to pressure changes detected by an air pressure sensor (not shown), the heater 36 vaporizes aerosolisable material delivered by the wick 37 to generate the aerosol, and this aerosol stream is then inhaled by a user through the opening in the mouthpiece 35. The aerosol is carried from the aerosol source to the mouthpiece 35 along an air channel (not shown in Figure 1) that connects the aerosol source to the mouthpiece opening as a user inhales on the mouthpiece.

[0306] In this particular example, the device 20 and article 30 are detachable from one another by separation in a direction parallel to the longitudinal axis, as shown in Figure 1 , but are joined together when the system 10 is in use by cooperating engagement elements 21, 31 (for example, a screw, magnetic or bayonet fitting) to provide mechanical and electricalconnectivity between the device 20 and the article 30, in particular connecting the heater 36 to the battery 14. The battery may be charged as is known to one skilled in the art.

[0307] In some embodiments, the article comprises / forms a sealed container. For example, the sealed container may be hermetically sealed. The hermetically sealed container may comprise a blister pack with one or more hermetically sealed compartments for storage of one or more articles comprising the formulation described herein.

[0308] In some embodiments, the article comprises a housing within which the formulation is contained. The housing may be transparent such that the formulation can be viewed from outside of the housing. It may also be that the housing has a degree of opacity such that the passage of light through the housing is limited. This can be important so as to prevent light (such as ultra violet light) from entering the housing and compromising the stability of the aerosolisable material. In some embodiments, the housing is formed from a material which inhibits / prevents the passage of ultra violet light there through. In some embodiments, it may be that the sealed container mentioned above is formed from a material which has a degree of opacity such that the passage of light through the sealed container is limited. Further, the sealed container mentioned above may be formed from a material which inhibits / prevents the passage of ultra violet light there through. This may be in addition to said sealed container being hermetically sealed and / or comprising a blister pack with one or more hermetically sealed compartments for storage of one or more articles comprising the aerosolisable material described herein.METHODS, PROCESS AND USES

[0309] In some embodiments described herein there is provided a process for forming an aerosol or a vapour, the process comprising providing an aerosolisable or vaporisable formulation as defined herein and aerosolising or vaporising the formulation. The process may alternatively comprise providing the aerosol provision system or vapour provision system defined herein and aerosolising or vaporising the formulation or consumable in the system.

[0310] According to some embodiments, there is provided the use of a consumable as defined herein to modify at least one sensory property of an aerosolisable or vaporisable formulation, such as wherein the sensory property is flavour, and the flavour is modified relative to the formulation without the consumable.

[0311] In some embodiments, there is provided the use of a consumable as defined herein to modify aroma of an aerosolisable or vaporisable formulation, wherein the aroma is modifiedrelative to the formulation without the consumable. In some embodiments the aroma is modified to replicate smoking a combustible tobacco product (e.g. a cigarette).

[0312] In some embodiments, there is provided the use of a consumable as defined herein to modify the flavour intensity of an aerosolisable or vaporisable formulation. In some embodiments, the use comprises increasing the flavour intensity of the aerosolisable or vaporisable formulation relative to the formulation without the consumable.

[0313] In some embodiments, there is provided the use of a consumable as defined herein to modify or improve at least one sensory property selected from taste, mouthfeel, in-smoking experience, and a combination thereof, of an aerosolisable or vaporisable formulation. The mouthfeel and / or in-smoking experience may include saturation, aftertaste, impact and nicotine hit, to replicate smoking a combustible tobacco product (e.g. a cigarette). The modification or improvement may be relative to the formulation without the consumable.

[0314] In some embodiments the use comprises modifying or improving taste of the formulation to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises modifying or improving mouthfeel of the formulation to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises modifying or improving saturation to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises modifying or improving aftertaste to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises modifying or improving nicotine hit to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises modifying or improving impact to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises modifying or improving in-smoking experience to replicate smoking a combustible tobacco product (e.g. a cigarette). In some embodiments the use comprises improving nicotine sensation to replicate smoking a combustible tobacco product (e.g. a cigarette).

[0315] In each of these uses, the aerosolisable or vaporisable formulation may be characterized according to the features and embodiments defined herein for the formulation and / or consumable.

[0316] These sensory properties may be measured by a trained sensory panel. A trained sensory panel is a team of trained assessors who define the sensory attributes (e.g. flavour including taste and aroma, mouthfeel and / or in-smoking experience) which best describeproducts that are being evaluated. The trained sensory panel ideally consists of smokers and / or dualists (i.e. users of cigarettes and e-cigarettes).

[0317] In some embodiments a method of preparing a formulation for a substance delivery system is provided, the method comprising:(a) reacting a C3 to C keto acid or a C2 to C carboxy-aldehyde with a polyhydric alcohol to form a product comprising one or more acetal, and(b) preparing the formulation with the reaction product comprising one or more acetal formed by step (a).

[0318] In some embodiments the substance delivery system is an aerosolisable or vaporisable formulation as described herein.

[0319] In one aspect, step (a) is conducted at least about 10 minutes before step (b). In one aspect, step (a) is conducted at room temperature or at an elevated temperature, preferably wherein the elevated temperature is from about 50 to about 80°C. In one aspect, step (a) is conducted at room temperature for at least about 10 minutes to about 24 hours, or wherein step (a) is conducted at an elevated temperature of from about 50 to 80°C for at least about 1 hour to about 5 hours.

[0320] In one aspect, step (a) is conducted at least about 10 minutes before step (b). In one aspect, step (a) is conducted at room temperature or at an elevated temperature, preferably wherein the elevated temperature is from about 50 to about 80°C. In one aspect, step (a) is conducted at room temperature for at least about 10 minutes to about 24 hours, or wherein step (a) is conducted at an elevated temperature of from about 50 to 80°C for at least about 1 hour to about 24 hours. In one aspect, step (a) is conducted at an elevated temperature of from about 50 to 80°C for at least about 1 hour to about 24 hours.

[0321] In some embodiments, a method of preparing a cartridge, as described herein, is provided. The method comprises placing the formulation, e.g. an aerosolisable formulation, as defined herein into a reservoir comprised within a housing of the cartridge.

[0322] In some embodiments, an aerosol comprising one or more acetals is described, wherein the acetal is a reaction product of a C3 to C keto acid and polyhydric alcohol, or a C2 to Cis carboxy-aldehyde and polyhydric alcohol, preferably wherein the C3 to C keto acid, the C2 to Cis carboxy-aldehyde and polyhydric alcohol.

[0323] The present invention will now be described with reference to the following non-limiting examples.EXAMPLESExample 1

[0324] An investigation was conducted to provide a sensory analysis of eliquids comprising organic acids and aerosol former materials. Due to the lability of certain organic acids, the invention sought to reduce the impact of said acids on the sensory properties of the eliquid. A further aim of the investigation was to determine ways in which migration of labile acids could be reduced without adversely affecting eliquid sensorial characteristics.

[0325] According to the present invention, it was found that sensory properties of eliquids could be maintained at a consistent level by forming acetals from (i) keto acids or carboxyaldehydes and (ii) polyhydric alcohols, such as glycerol. Moreover, it was observed that loss of acid was mitigated by forming said acetal compounds.

[0326] Figures 2 and 3 illustrate embodiments of the invention. Levulinic acid (150mg) was premixed with 15g of a polyhydric alcohol (Figure 2 = glycerol; Figure 3 = glycerol and propylene glycol in a 50:50 weight ratio). The consumable formulations were heated (Fisherbrand Isotemp) for 2 hours at 70°C and with stirring at 1500rpm. Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 10 times (10k dilution) using a solvent (water / methanol, 8:2) for characterisation. Characterisation was used for qualitative and quantitative purposes.

[0327] Where levulinic acid was combined with glycerol only, the concentration of levulinic acid in the consumable was reduced (6.4 pg / mL vs 9.4 pg / mL) and theoretical conversion to acetals (3-(5-hydroxy-2-methyl-1,3-dioxan-2-yl)propanoic acid and 3-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)propanoic acid) was increased (49.2% vs 18.4%) relative to corresponding consumables comprising a mixture of glycerol and propylene glycol. Theoretical conversion was determined based upon the levulinic acid concentration at T= 0 (i.e. at the point of formulation; (i) levulinic acid concentration in glycerol = 12.6 pg / mL; (ii) levulinic acid concentration in glycerol / propylene glycol = 11.5 pg / mL) and the levulinic acid concentration quantitatively determined after heating.

[0328] Figures 4 and 5 illustrate embodiments of the invention, where Levulinic acid (150mg) was premixed with 15g of a polyhydric alcohol (i.e. glycerol). The consumable formulations were stored for 18 hours at room temperature (approx. 20°C). Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 10 times (10k dilution) using a solvent (water / methanol, 8:2) for characterisation. Characterisation was used for qualitative and quantitative purposes.

[0329] The concentration of levulinic acid in the consumable reduced on storage (6.5 pg / mL vs 3.8 pg / mL) and theoretical conversion to acetals (3-(5-hydroxy-2-methyl-1,3-dioxan-2-yl)propanoic acid and 3-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)propanoic acid) increased (48.6% vs 70.1%) after storage. Theoretical conversion was determined based upon the levulinic acid concentration at T=0 (i.e. at the point of formulation; levulinic acid concentration = 12.6 pg / mL) and the levulinic acid concentration quantitatively determined after storage.

[0330] Figure 6 illustrates an eliquid prepared without premixing the organic acid (levulinic acid) and glycerol. The eliquid consisted essentially of glycerol and propylene glycol in a 50:50 weight ratio, 10mg / ml nicotine, levulinic acid and menthol. The consumable formulations were stored for 7 days at room temperature (approx. 20°C). Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 1 time (1k dilution) using a solvent (water / methanol, 8:2) for characterisation. Characterisation was used for qualitative and quantitative purposes.

[0331] Levulinic acid concentration was found to decrease after storage, relative to the levulinic acid concentration at T=0, i.e. at the point of formulation (levulinic concentration at T=0 - 11.5 pg / mL; levulinic concentration after storage - 11.3 pg / mL; reduction of 1.4%). No acetal derivatives of levulinic acid or glycerol were qualitatively observed (LCD = 0.5ppm).Example 2

[0332] Further investigation of acetal formation was carried out in accordance with the present invention.

[0333] 4-formylbenzoic acid was mixed with 15g of a polyhydric alcohol (i.e. glycerol) and characterised at TO (cf. Fig 7; 7A = 0.1% 4-formylbenzoic acid in glycerol; 7B = 0.1% 4-formylbenzoic acid in solvent). Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulation was diluted 1 time (1k dilution) using the polyhydric alcohol and additionally a solvent (water / ethanol, 5:5) for characterisation.

[0334] The consumable formulations were stirred using magnetic stirrer at 1500 rpm and reacted for 2 hours and 20 hours at 80°C. Spectroscopic characterisation of the consumable formulations are illustrated in Figure 8 (2hrs) and Figure 9 (20hrs). The concentration of 4-formylbenzoic acid (8A I 9A; EIC = 149.0245) in the consumable reduced on storage and theoretical conversion to acetals (2-(4-carboxyphenyl)-1,3-dioxolane-4-methanol and 2-(4-carboxyphenyl)-1,3-dioxan-5-ol) (cf. 8B I 9B; EIC = 223.0611) increased after storage. Yield was higher after an extended mixing step (20h; cf. Fig 9) relative to a shorter period (2h; cf. Fig. 8). Theoretical conversion was determined based upon the 4-formylbenzoic acid concentration at T=0 in the solvent.

[0335] Glyoxylic acid was mixed with 15g of a polyhydric alcohol (i.e. glycerol). The consumable formulations were stirred using magnetic stirrer at 1500 rpm and reacted for 2 hours at 80°C. Spectroscopic characterisation of the consumable formulation is illustrated in Figure 8 Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 1 times (1k dilution) using a solvent (water / ethanol, 5:5) for characterisation. Characterisation was used for qualitative and quantitative purposes.

[0336] The concentration of glyoxylic acid (10A; EIC = 72.9932) in the consumable reduced on storage and theoretical conversion to acetals ((2-carboxy-1,3-dioxolan-4-yl)methanol and 2-carboxy-1,3-dioxan-5-ol) (cf. 10B; EIC = 147.0299) increased after storage (cf Fig. 10). Theoretical conversion was determined based upon the glyoxylic acid concentration at T=0 in the solvent .

[0337] Figures 11 and 12 illustrate an embodiment of the invention, where pyruvic acid (150mg) was premixed with 15g of a polyhydric alcohol (i.e. glycerol) and characterised at TO (cf. Fig 11; 11A = 1% pyruvic acid in solvent; 11 B = 1% pyruvic acid in glycerol; 11C = 10%pyruvic acid in glycerol). Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 1 time (1k dilution) and 10 times (10k dilution) using the polyhydric alcohol and additionally a solvent (water / ethanol, 5:5) for characterisation.

[0338] The consumable formulations were stirred using magnetic stirrer at 1500 rpm and reacted for 20 hours at 80°C. The concentration of pyruvic acid in the consumable reduced on storage (cf. 12A; EIC = 87.0082) and theoretical conversion to acetals (4-(hydroxymethyl)-2-methyl-1,3-dioxolane-2-carboxylic acid and 5-hydroxy-2-methyl-1,3-dioxane-2-carboxylic acid) (cf. 12B = 1% pyruvic acid in glycerol, EIC = 161.0453; 12C = 10% pyruvic acid in glycerol, EIC = 161.0453) increased after storage. Theoretical conversion was determined based upon the pyruvic acid concentration at T=0 in the solvent.

[0339] Figures 13 and 14 illustrate an embodiment of the invention, where pyruvic acid (150mg) was premixed with 15g of a polyhydric alcohol (i.e. 2-methyl-1,3-propanediol) and characterised at TO (cf. Fig 13; 13A = 1% pyruvic acid in solvent; 13B = 1% pyruvic acid in 2-methyl-1,3-propanediol; 13C = 10% pyruvic acid in 2-methyl-1,3-propanediol). Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 1 time (1k dilution) and 10 times (10k dilution) using the polyhydric alcohol and additionally a solvent (water / ethanol, 5:5) for characterisation.

[0340] The consumable formulations were stirred using magnetic stirrer at 1500 rpm and reacted for 20 hours at 80°C. The concentration of pyruvic acid in the consumable reduced on storage (cf. 14A; EIC = 87.0082) and theoretical conversion to an acetal (2-(5-methyl-1,3-dioxan-2-yl)propanoic acid) (cf. 14B = 1% pyruvic acid in 2-methyl-1,3-propanediol, EIC = 159.0665; 14C = 10% pyruvic acid in 2-methyl-1,3-propanediol, EIC = 159.0664) increased after storage. Theoretical conversion was determined based upon the pyruvic acid concentration at T=0 in the solvent.

[0341] Figures 15 and 16 illustrate an embodiment of the invention, where a-ketoglutaric acid (150mg) was premixed with 15g of a polyhydric alcohol (i.e. 2-methyl-1,3-propanediol) and characterised at TO (cf. Fig 15; 15A = 1% a-ketoglutaric acid in solvent; 15B = 1% a-ketoglutaric acid in 2-methyl-1,3-propanediol; 15C = 10% a-ketoglutaric acid in 2-methyl-1,3-propanediol). Characterisation of the formulation was undertaken using liquid chromatography (Agilent Infinity 1290 series) coupled to quadrupole time-of-flight mass spectrometer (Bruker timsTOF Pro) and liquid chromatography (Agilent Infinity 1290 series) coupled to triple quadrupole (Sceix triple quadrupoles 6500+) mass spectrometer. The consumable formulations were diluted 1 time (1k dilution) and 10 times (10k dilution) using the polyhydric alcohol and additionally a solvent (water / ethanol, 5:5) for characterisation.

[0342] The consumable formulations were stirred using magnetic stirrer at 1500 rpm and reacted for 20 hours at 80°C. The concentration of a-ketoglutaric acid in the consumable reduced on storage (cf. 16A; EIC = 145.0143) and theoretical conversion to acetals (4-(2-hydroxy-5-methyl-1 ,3-dioxan-2-yl)-2-oxobutanoic acid, 4-(2-hydroxy-5-methyl-1 ,3-dioxan-2-yl)-4-oxobutanoic acid and 2-(2-carboxyethyl)-5-methyl-1,3-dioxane-2-carboxylic acid) (cf.16B = 1% pyruvic acid in 2-methyl-1,3-propanediol, EIC = 217.0717; 16C = 10% pyruvic acid in 2-methyl-1,3-propanediol, EIC = 217.0717) increased after storage. Theoretical conversion was determined based upon the pyruvic acid concentration at T=0 in the solvent.

[0343] This information further demonstrates the formation of acetals in different pre-mixture compositions comprising polyols and keto acids.

[0344] 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.

Claims

CLAIMS1. A consumable for an aerosolisable or vaporisable formulation, wherein the consumable comprises one or more acetals, the acetals being a reaction product of a C3 to Cis keto acid and a polyhydric alcohol, or a C2 to C carboxy-aldehyde and a polyhydric alcohol.

2. The consumable according to claim 1, wherein the polyhydric alcohol is glycerol.

3. The consumable according to claim 1 or claim 2, wherein the consumable further comprise one or more active agents, preferably wherein the active agent is nicotine.

4. The consumable according to any preceding claim, wherein the consumable further comprises an aerosol former material in addition to the polyhydric alcohol or a substrate material, optionally wherein the aerosol former material is present in an amount of at least about 70 wt%, based on the total weight of the consumable, or wherein the substrate material comprises a carrier material, a porous material, or a combination thereof.

5. The consumable according to any preceding claim, wherein the consumable further comprises propylene glycol, water, or a combination thereof.

6. The consumable according to any preceding claim, wherein the one or more acetals are present in an amount of about 0.001 wt% to about 10 wt%, based on the total weight of the consumable, preferably about 0.01 wt% to about 10 wt%, based on the total weight of the consumable.

7. The consumable according to any preceding claim, wherein the one or more acetals comprise a reaction product of a C3 to C keto acid and polyhydric alcohol, preferably wherein the keto acid is a C3 to C12 keto acid.

8. The consumable according to any preceding claim, wherein the one or more acetals comprise a reaction product of a C2 to C carboxy-aldehyde and polyhydric alcohol, preferably wherein the carboxy-aldehyde is a C2 to C12 carboxy-aldehyde.

9. The consumable according to any preceding claim, wherein the keto acid or carboxyaldehyde is represented by formula (I):wherein n is an integer from 0 to 6;wherein Ri is selected from H, Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra, or C(O)ORa; andwherein each R2 is independently selected from H, OH, CH(O), C(O)Ra, orCi-6 alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Ra;wherein Rais Ci-e alkyl or alkenyl, optionally substituted by OH, or OH; provided that at least one CH(O) group is present for the carboxy-aldehyde, and the total number of carbon atoms is from 2 to 18 for the carboxy-aldehyde and from 3 to 18 for the keto acid.

10. A formulation for a substance delivery system, wherein the formulation comprises polyhydric alcohol, an active agent, and one or more acetals, the acetals being represented by formula (II):wherein m is an integer from 0 to 6;each X is independently selected from CH2, CHRb, CRbRc, or O;R3 is H and R4 is selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb; orR3 and R4 are independently selected from Ci-e alkyl or alkenyl, optionally substituted by OH, CH(O) or C(O)Rb, or C(O)ORb;each of R5 and Re are independently selected from H, Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rb is selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH;each Rcis selected from Ci-e alkyl or alkenyl, optionally substituted by Ci-e alkyl or alkenyl, OH, CH(O) or C(O)Rb, or C(O)ORb, or OH; andwherein at least one of R3, R4, Rs, Re, Rb and / or Rcis substituted by C(O)OH.

11. The formulation according to claim 10, wherein the formulation further comprises one or more organic acids, preferably wherein the one or more organic acids are selected from the group: acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, isobutyric acid, butyric acid, methylbutyric acid, 2-methylbutyric acid, 3-methylpentanoic acid, isovaleric acid, valeric acid, hexanoic acid, hepatanoic acid, octanoic acid, nonanoic acid, methylvaleric acid, decanoic acid, glycolic acid, 2-butenedioic acid (Z), 2-butenedioic acid (E), succinic acid, glyceric acid, malic acid, pyroglutamic acid, trihydroxybutanoic acid, tetrahydroxypentanoic acid, 2-keto-L-gluconic acid, quinic acid, gluconic acid, galactaric acid, hexadecanoic acid, caffeic acid, linoleic acid, linolenic acid, glucuronic acid, chlorogenic acid, fumaric acid, maleic acid, oxalic acid, oxaloacetic acid, acetoacetic acid, beta-hydroxybutyric acid, alpha-ketoglutaric acid, alpha-ketobutyric acid and mixtures thereof.

12. The formulation according to claim 10 or claim 11, wherein the formulation further comprises levulinic acid.

13. An aerosol comprising one or more acetal, wherein the acetal is a reaction product of a C3 to Cis keto acid and polyhydric alcohol, or a C2 to C carboxy-aldehyde and polyhydric alcohol, preferably wherein the C3 to Cis keto acid, the C2 to C carboxy-aldehyde and polyhydric alcohol are defined as in any preceding claim 1 to 9.

14. A vaporisable formulation for a vapour provision system comprising the consumable according to any preceding claim, and a substrate material, preferably wherein the formulation comprises one or more organic acids.

15. The vaporisable formulation according to claim 14, wherein the substrate material comprises a carrier material, a porous material, or a combination thereof.

16. A container or package containing the consumable according to any preceding claim 1 to 9, preferably wherein the container or package is a pouched oral product comprising a saliva permeable pouch, or a cartridge for an aerosol provision system.

17. A substance delivery system comprising the consumable of any preceding claim 1 to 9, or the container or package of claim 16.

18. The substance delivery system of claim 17, wherein the system is a combustible aerosol provision system, a non-combustible aerosol provision system or an aerosol-free delivery system.

19. A method of preparing a formulation for a substance delivery system, preferably an aerosolisable or vaporisable formulation, the method comprising:(a) reacting a C3 to C keto acid or a C2 to C carboxy-aldehyde with polyhydric alcohol to form a product comprising one or more acetals, and(b) preparing the formulation with the reaction product comprising one or more acetals formed by step (a).

20. The method according to claim 19, wherein step (a) is conducted at room temperature or at an elevated temperature, preferably wherein the elevated temperature is from about 50 to about 80°C.

21. The method according to any preceding claim 19 or 20, wherein the C3 to C keto acid or the C2 to C carboxy-aldehyde is as defined in any of claims 1 to 9.

22. The method according to any preceding claim 19 to 21 , wherein step (a) is conducted at room temperature for at least about 10 minutes to about 24 hours, or wherein step (a) is conducted at an elevated temperature of from about 50 to 80°C for at least about 1 hour to about 5 hours.

23. An aerosolisable or vaporisable formulation obtained by the method according to any of claims 19 to 22.

24. A cartridge for an aerosol provision system, the cartridge comprising the aerosolisable formulation according to any of claims 10 to 14 or 23.

25. A method of preparing the cartridge according to claim 24, wherein the method comprises placing the aerosolisable formulation according to any of claims 10 to 14 or 23 into a reservoir comprised within a housing of the cartridge.

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