Patent Description:
Electronic aerosol provision systems such as e-cigarettes generally contain a reservoir of liquid which is to be vaporised, typically containing nicotine. When a user inhales on the device, a heater is activated to vaporise a small amount of liquid, which is therefore inhaled by the user.

<CIT> discloses an electronic aerosol provision system comprising an improved vaping fluid.

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

One challenge faced in providing such systems is to provide from the aerosol provision device an aerosol to be inhaled which provides consumers with an acceptable experience. 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. Nicotine contributes to a number of these factors, and is strongly associated with factors such as impact, irritation and smoothness; these are readily perceived by consumers, and e-cigarettes may offer too much or too little of these parameters for consumers, depending upon individual preferences. Nicotine reward is particularly complex as it results from both the amount of and speed with which nicotine is absorbed from the lining of the mouth, this is typically nicotine in the vapour phase, and from the amount and speed nicotine that is absorbed from the lungs, this is typically nicotine in the particulate phase of the aerosol which is inhaled. Each of these factors, and their balance, can strongly contribute to consumer acceptability of an e-cigarette. Providing means to optimise the overall vaping experience is therefore desirable to e-cigarette manufacturers.

A further challenge facing such systems is the continued demand for harm reduction. Harm from cigarette and e-cigarette devices primarily comes from toxicants. Therefore, there is a desire to reduce or remove the components which may form toxicants.

In one aspect there is provided an aerosolisable formulation comprising.

wherein in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.

In one aspect there is provided an aerosolisable formulation comprising.

In one aspect there is provided a process for forming an aerosol, the process comprising aerosolising an aerosolisable formulation comprising.

In one aspect there is provided a contained aerosolisable formulation comprising.

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

In one aspect there is provided a process for improving the sensory properties of an aerosolised formulation, the process comprising the steps of aerosolising an aerosolisable formulation comprising.

As discussed herein in one aspect there is provided an aerosolisable formulation comprising (i) water; (ii) one or more flavours to be encapsulated; (iii) one or more encapsulating materials selected from the group consisting of substituted (α)-cyclodextrin, substituted (β)-cyclodextrin, substituted (γ)-cyclodextrin, and mixtures thereof; and (iv) nicotine; wherein in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.

We have found that an advantageous system may be provided in which, in the presence of water, the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. We have found that by selection of one or more encapsulating materials together with selection of the one or more flavours to be encapsulated such that the two materials have the required energy of binding an advantageous flavour delivery system is provided. In particular, the flavour delivery system binds the flavour strongly enough for it to be delivered in use but not so strongly that it will not dissociate in use from the encapsulating material. Thus a flavour may be stably delivered whilst still providing a strong flavour release for the end user.

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

Reference in the specification to protonated form means both monoprotonated nicotine and diprotonated nicotine. Reference in the specification to amounts in the protonated form means the combined amount of monoprotonated nicotine and diprotonated nicotine. Furthermore, when reference is made to a fully protonated formulation it will be understood that at any one time there may be very minor amounts of unprotonated nicotine present, e.g. less than <NUM>% unprotonated.

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.

As discussed herein, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.

In one aspect the energy of binding may be determined by molecular modelling and, in particular, using docking performed in Autodock <NUM> [The Scripps Research Institute, La Jolla, CA, USA] (<NPL>). The docking performed in Autodock <NUM> may be performed using the following settings:.

Grid Point Spacing (Angstroms): <NUM>
Number of grid points in each Cartesian direction.

User-specified initial position for ligand: random
Initial relative dihedral offset: random
User-specified initial relative dihedrals: random
Docking search parameter: Genetic Algorithm
Number of requested GA dockings: <NUM> runs
Population size: <NUM>
Maximum number of evaluations: <NUM>
Maximum number of top individuals that automatically survive: <NUM>
Rate of gene mutation: <NUM>
Rate of crossover: <NUM>
GA crossover mode: "twopt"
Mean of Cauchy distribution for gene mutation(alpha parameter): <NUM>
Variance of Cauchy distribution for gene mutation(beta parameter): <NUM>
Number of generations fro picking worst individuals : <NUM>
Docking output: Lamarckian GA.

In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.

In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol. In one aspect, in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.

As discussed herein the aerosolisable formulation contains water. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of at least <NUM> wt. % based on the aerosolisable formulation.

In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation. In one aspect water is present in an amount of from <NUM> to <NUM> wt. % based on the aerosolisable formulation.

The use of water allows for the replacement of some or all of the glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof typically used in e-cigarettes. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains no glycerol, propylene glycol, <NUM>,<NUM>-propane diol and mixtures thereof.

In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol, propylene glycol, and mixtures thereof in a combined amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains no glycerol, propylene glycol, and mixtures thereof.

In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains glycerol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains no glycerol.

In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains propylene glycol in an amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the aerosolisable formulation contains no propylene glycol.

Nicotine formulations may be provided having desirable properties of flavour, impact, irritation, smoothness and/or nicotine reward for the user. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of no greater than <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation. In one aspect nicotine is present in an amount of from <NUM> to <NUM> wt% based on the total weight of the aerosolisable formulation.

The formulation may comprise nicotine in protonated form. The formulation may comprise nicotine in unprotonated form. In one aspect the formulation comprises nicotine in unprotonated form and nicotine in monoprotonated form. In one aspect the formulation comprises nicotine in unprotonated form and nicotine in diprotonated form. In one aspect the formulation comprises nicotine in unprotonated form, nicotine in monoprotonated form and nicotine in diprotonated form.

In one aspect at least 5wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 10wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 15wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 20wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 25wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 30wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 35wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 40wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 45wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 50wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 55wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 60wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 65wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 70wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 75wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 80wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 85wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 90wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 95wt% of the nicotine present in the formulation is in protonated form. In one aspect at least 99wt% of the nicotine present in the formulation is in protonated form. In one aspect at least <NUM>. 9wt% of the nicotine present in the formulation is in protonated form.

In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form. In one aspect from <NUM> to <NUM> wt% of the nicotine present in the formulation is in protonated form.

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, <NUM>-(<NUM>-methylpyrrolidin-<NUM>-yl) pyridine, is a diprotic base with pKa of <NUM> for the pyridine ring and <NUM> for the pyrrolidine ring It can exist in pH-dependent protonated (mono- and di-) and non-protonated (free base) forms which have different bioavailability.

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

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 di- depending on the pH). If the relative fraction of protonated nicotine and the total amount of nicotine in the sample are known, the absolute amount of protonated nicotine can be calculated.

The relative fraction of protonated nicotine in formulation can be calculated by using the 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:
<CHM>.

The Henderson-Hasselbalch equation for this equilibrium is: <MAT>.

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=<NUM>). 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: <MAT>.

Determination of pKa values of nicotine formulations was carried out using the basic approach described in "<NPL>.

In one aspect the aerosolisable formulation further comprises an acid. The acid may be any suitable acid. In one aspect the acid is an organic acid. In one aspect the acid is a carboxylic acid. In one aspect the acid is an organic carboxylic acid.

In one aspect the acid is selected from the group consisting of acetic acid, lactic acid, formic acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid, tartaric acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof. In one aspect the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, lactic acid, sorbic acid, and mixtures thereof. In one aspect the acid is selected from the group consisting of citric acid, benzoic acid, levulinic acid, and mixtures thereof. In one aspect the acid is at least citric acid. In one aspect the acid consists of citric acid.

In one aspect the acid is selected from acids having a pka of from <NUM> to <NUM>. In one aspect the acid is a weak acid. In one aspect the acid is a weak organic acid.

In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>. In one aspect the acid has a solubility in water of at least <NUM>/L at <NUM>.

The molar ratio of acid to nicotine may be selected as desired. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of acid to nicotine is from <NUM>:<NUM> to <NUM>:<NUM>.

In one aspect the total content of acid present in the formulation is no greater than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no greater than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no greater than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no greater than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no greater than <NUM> mole equivalents based on the nicotine.

In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine. In one aspect the total content of acid present in the formulation is no less than <NUM> mole equivalents based on the nicotine.

The acid may be present in any suitable amount. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of no greater than <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation. In one aspect the acid is present in an amount of from <NUM> to <NUM> wt% based on the aerosolisable formulation.

The amount of acid and the solubility of the acid may be selected such that a given amount of the acid will dissolve in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water. In one aspect at <NUM> at least <NUM>% of the acid dissolves in the water.

The aerosolisable formulation comprises one or more flavours or flavouring components. As used herein, the terms "flavour" and "flavourant" refer to materials which, where local regulations permit, may be used to create a desired taste or aroma in a product for adult consumers. They may include extracts (e.g. liquorice, hydrangea, Japanese white bark magnolia leaf, chamomile, fenugreek, clove, menthol, 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, piment, ginger, anise, coriander, coffee, or a mint oil from any species of the genus Mentha), flavour enhancers, bitterness receptor site blockers, sensorial receptor site activators or stimulators, sugars and/or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharine, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, botanicals, or breath freshening agents. They may be imitation, synthetic or natural ingredients or blends thereof. They may be in any suitable form, for example, oil, liquid, or powder.

The one or more flavours may be selected from <NUM>-(<NUM>-Methoxyphenyl)-<NUM>-butanone [also known as (<NUM>-(para-)methoxyphenyl)-<NUM>-butanone], <NUM>-Hydroxy-<NUM>-methoxybenzaldehyde [also known as vanillin], <NUM>-heptyloxolan-<NUM>-one [also known as γ-undecalactone], (<NUM>,5R)-<NUM>-Isopropyl-<NUM>-methylcyclohexanone [also known as menthone], <NUM>-ethoxy-<NUM>-[(E)-prop-<NUM>-enyl]phenol [also known as <NUM>-propenyl guaethol], (1R,<NUM>,5R)-<NUM>-methyl-<NUM>-propan-<NUM>-ylcyclohexan-<NUM>-ol [also known as menthol], <NUM>-(<NUM>-Mercapto-<NUM>-methylethyl)-<NUM>-methylcyclohexanone [also known as para-mentha-<NUM>-thiol-<NUM>-one] and mixtures thereof. In one aspect the flavour is at least menthol.

If present, the one or more flavours may be present in any suitable amount. In one aspect the one or more flavours are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of no greater than 2wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of no greater than 1wt. % based on the aerosolisable formulation.

In one aspect the one or more flavours are present in a total amount of from <NUM> to 5wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of from <NUM> to 4wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of from <NUM> to 3wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of from <NUM> to 2wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of from <NUM> to 1wt. % based on the aerosolisable formulation. In one aspect the one or more flavours are present in a total amount of from <NUM> to <NUM>. % based on the aerosolisable formulation.

The aerosolisable formulation comprises one or more encapsulating materials. The one or more encapsulating materials may be present in any suitable amount in the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more encapsulating materials are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation.

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

In one aspect the one or more cyclodextrins is selected from substituted (β)-cyclodextrins. Chemical substitutions at the <NUM>-, <NUM>-, and <NUM>-hydroxyl sites are envisaged, and in particular substitution at the <NUM>-position.

In one aspect the one or more cyclodextrins are selected from the group consisting of <NUM>-hydroxy-propyl-α-cyclodextrin, <NUM>-hydroxy-propyl-β-cyclodextrin, <NUM>-hydroxy-propyl-γ-cyclodextrin and mixtures thereof. In one aspect the one or more cyclodextrins is at least <NUM>-hydroxy-propyl-α-cyclodextrin. In one aspect the one or more cyclodextrins is at least <NUM>-hydroxy-propyl-β-cyclodextrin. In one aspect the one or more cyclodextrins is at least <NUM>-hydroxy-propyl-γ-cyclodextrin.

<NUM>-hydroxy-propyl derivatives of cyclodextrins, such as <NUM>-hydroxy-propyl-β-cyclodextrin have increased solubility in water when compared to base cyclodextrins such as β-cyclodextrin.

One or more cyclodextrins may or may not be present in any suitable amount in the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation. In one aspect the one or more cyclodextrins are present in a total amount of no greater than <NUM> wt. % based on the aerosolisable formulation.

As discussed herein, in one aspect the present invention provides an aerosolisable formulation comprising (i) water (ii) one or more flavours to be encapsulated; and (iii) one or more encapsulating materials selected from the group consisting of substituted (α)-cyclodextrin, substituted (β)-cyclodextrin, substituted (γ)-cyclodextrin, and mixtures thereof having a solubility in water of at least <NUM>% of the solubility in water of the one or more flavours to be encapsulated; and (iv) nicotine.

In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated. In one aspect, the one or more encapsulating materials have a solubility in water of at least <NUM> % of the solubility in water of the one or more flavours to be encapsulated.

The one or more encapsulating materials and the flavour may be present in any suitable amount relative to each other. The molar ratio of encapsulating material to flavour may be selected as desired. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is from <NUM>:<NUM> to <NUM>:<NUM>. In one aspect the molar ratio of encapsulating material to flavour is approximately <NUM>:<NUM>.

As discussed herein, in one aspect there is provided a process for improving the sensory properties of an aerosolised nicotine formulation, the process comprising the steps of aerosolising an aerosolisable formulation comprising.

As discussed herein, in one aspect there is provided a process for forming an aerosol, the process comprising aerosolising an aerosolisable formulation comprising (i) water (ii) one or more flavours to be encapsulated; and (iii) one or more encapsulating materials selected from the group consisting of substituted (α)-cyclodextrin, substituted (β)-cyclodextrin, substituted (γ)-cyclodextrin, and mixtures thereof; wherein in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.

In the process the aerosol may be formed by a process performed at a temperature below <NUM>. In the process the aerosol may be formed by a process performed at a temperature below <NUM>. In the process the aerosol may be formed by a process performed at a temperature below <NUM>. In the process the aerosol may be formed by a process performed at a temperature below <NUM>. In the process the aerosol may be formed by a process performed at a temperature below <NUM>. In the process the aerosol may be formed by a process which does not involve heating.

In the process the aerosol may be formed by applying ultrasonic energy to the aerosolisable formulation.

In one aspect the aerosol the aerosol of the aerosolised formulation has a D50 of from <NUM> to <NUM>. References in the present specification to particle size distribution, D50, D10 or D90 refer to values measured in accordance with British and European Pharmacopoeia, <NUM>. <NUM> Particle Size Analysis By Laser Light Diffraction (see <NPL>). European Pharmacopoeia. Strasbourg, France: Council of Europe). The terms D50, Dv50 and Dx50 are interchangeable. The terms D10, Dv10 and Dx10 are interchangeable. The terms D90, Dv90 and Dx90 are interchangeable.

In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>. In one aspect the aerosol has a D50 of from <NUM> to <NUM>.

In one aspect the aerosol has a D10 of at least <NUM>. In one aspect the aerosol has a D10 of at least <NUM>. In one aspect the aerosol has a D10 of at least <NUM>.

In one aspect the aerosol has a D90 of no greater than <NUM>. In one aspect the aerosol has a D90 of no greater than <NUM>. In one aspect the aerosol has a D90 of no greater than <NUM>.

In one aspect D50 is measured after exclusion of particles having a particle size of less than <NUM>. In one aspect D10 is measured after exclusion of particles having a particle size of less than <NUM>. In one aspect D90 is measured after exclusion of particles having a particle size of less than <NUM>.

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

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

In one aspect the container is part of an e-cigarette. Therefore in a further aspect the present invention provides an electronic aerosol provision system comprising: an aerosolisable formulation as defined herein; an aerosoliser for aerosolising formulation for inhalation by a user of the electronic aerosol provision system; and a power supply comprising a cell or battery for supplying power to the aerosoliser.

In addition to the aerosolisable formulation of the present invention and to systems such as containers and electronic aerosol provision systems containing the same, the present invention provides a process for improving the sensory properties of an aerosolised nicotine.

Reference to an improvement in the sensory properties of a vaporised nicotine solution refer may include an improvement in the smoothness of the vaporised nicotine solution as perceived by a user.

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

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

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

The binding and energy of binding of hydroxypropyl beta cyclodextrin and menthol was studied with automated docking simulations. Automated docking simulations use a three-dimensional representation to assess the fit for a guest substrate in a molecular cavity. It is generally accepted that the predicted binding energies may be accurately determined with automated docking simulations.

Docking was performed in Autodock <NUM> [The Scripps Research Institute, La Jolla, CA, USA] (Morris, et al. , <NUM>) using settings as detailed below. In brief, hydrogens were merged and Kolman/Gasteiger charges were added according to standard methodology. Grid size was adjusted where necessary to accommodate the receptor. In general, settings were left at default values. The receptors were treated as rigid entities. Output format was Lamarckian genetic algorithm.

Hydroxypropyl-beta-CD (HP-β-CD) contains numerous isomers, due to random substitution during synthesis. The primary hydroxyl groups at the C-<NUM> of the sugars are the most likely to be substituted owing to their nucleophilicity and lack of steric crowding, but substitution can also occur at the C-<NUM> and C-<NUM> positions, which are at the opposite face of the cavity to C-<NUM>. The crystal structures of beta (β) cyclodextrin were taken from The Cambridge Crystallographic Data Centre (CCDC) (item designation "ARUXIU") and modified with hydroxypropyl groups according to several substitution patterns to see how important this is to binding.

These modifications were made using Discovery Studio Visualizer [v16. <NUM>, (<NUM>), Dassault Systémes Biovar Corp]. The structures were then optimized with the fast, Dreiding-like force field tool within Discovery Studio Visualizer and converted to. pdb format for onward processing using Autodock <NUM>. The settings used in the modelling each of Versions <NUM>, <NUM> and <NUM> are provided in the table below.

The <NUM>-dimensional structure for menthol was obtained from Pubchem and converted to. pdb format for use in docking simulation.

The docking simulation defaults to <NUM> repetitions to check for viable conformations between host and guest. Therefore, each simulation gives <NUM> results. The result is expressed in terms of Gibbs free energy of binding. A negative value denotes an energetically favoured process. The absolute size of this binding energy is a useful comparator of binding affinity. As a general rule, negative values with an absolute size above around <NUM> Kcal / mole indicate moderately strong binding affinity. The full data for each version are given in docking log files herein but are summarised below, along with an image showing a representative binding complex for each version.

The docking simulation gave several conformations, in all cases binding the guest within the cavity of the host - as typified by <FIG>, which shows atomic spheres for the host and a line representation for the guest to improve clarity. The corresponding docking log file is named menBCD.

The runs provided a free energy of binding of -<NUM> Kcal/mole.

The docking simulation gave several conformations, in all cases binding the guest within the cavity of the host - as typified by <FIG>, which shows atomic spheres for the host and a line representation for the guest to improve clarity.

The binding of menthol in hydroxypropyl beta cyclodextrin can be modelled using molecular docking, which establishes a binding free energy of between -<NUM> and -<NUM> Kcal/mole.

The extent and location of the hydroxypropyl groups in HP-β-CD can vary from molecule to molecule. We therefore checked the docking process using a range of possible structures to ensure sensitivity of the measurement towards fluctuations in structure. Two versions of the hydroxypropyl derivative of cyclodextrin were assessed, and gave broadly similar results. An unfunctionalized variant was also assessed, and gave reasonably similar results.

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.

Aspects of the invention are also provided in which Hansen sphere values for one or more encapsulating materials are selected to achieve desirable compatibility with flavours included in the aerosolisable formulation, and with nicotine, if present. As will be understood by one skilled in the art Hansen sphere values describe the interaction between flavours and the encapsulating material. The relevant measurements are:.

The closer these values are for flavour and solvent (water) the more soluble they will be. Through selection of the Hansen sphere values the encapsulating material encapsulates at least one of the one or more flavours in preference to other components such as nicotine.

As will be understood by one skilled in the art compatibility between encapsulating material (host) and the encapsulated species (guest) can be defined as how "alike" they are. This can also be measured using the Hansen Solubility Parameters (HSP) Distance (also termed Ra in the equation below) between the host and guest molecules. <MAT> where,.

Likeness can then be determined using the Ra of the system and an interaction radius of the guest molecule (termed Ri) as shown below: <MAT> where,.

Claim 1:
An aerosolisable formulation comprising
(i) water;
(ii) one or more flavours to be encapsulated;
(iii) one or more encapsulating materials selected from the group consisting of substituted (α)-cyclodextrin, substituted (β)-cyclodextrin, substituted (γ)-cyclodextrin, and mixtures thereof; and
(iv) nicotine;
wherein in the presence of water the energy of binding of the one or more encapsulating materials with the one or more flavours to be encapsulated is from -<NUM> to -<NUM> kcal/mol.