NANODISPERSION AND METHOD OF FORMATION THEREOF

The present invention relates to nanodispersions. In particular but not exclusively the invention relates to a method of forming a stable nanodispersion and to a nanodispersion produced thereby. The invention also relates to a method of forming a transparent nanodispersion, in particular a transparent nanoemulsion, and to a method of forming a dilutable nanodispersion.

BACKGROUND

It is known to produce emulsions of two immiscible substances whereby one substance (the 'dispersed phase') is dispersed in the other (the 'continuous phase'). Emulsions are thermodynamically unstable and do not form spontaneously. Rather, energy must be input through shaking, stirring or other comminution technique. However, emulsions may be stabilized kinetically by the addition of substances which prevent droplet coalescence when droplets collide or suppress 'ripening' processes in which large droplets grow at the expense of small droplets.

It is desirable to form a dispersion of nanoparticles (herein referred to as a 'nanodispersion') in which the dispersed phase is in the form of particles having a diameter below 100nm. It is also desirable to be able to form a nanodispersion that is stable over periods of weeks and years, even when the dispersed phase is further diluted by the addition of a further quantity of the continuous phase.

STATEMENT OF THE INVENTION

In a first aspect of the invention there is provided a method of forming a stable nanodispersion comprising the steps of:

(a) providing a host fluid, a particle fluid to be dispersed in the host fluid and a stabiliser; and

(b) subjecting the host fluid, the particle fluid and the stabiliser to a high shear comminution process whereby a dispersion of particles of the particle fluid in the host fluid is formed, the particles of the particle fluid having a Sauter mean diameter of substantially 100nm or less, wherein an amount of stabiliser comprised in the medium corresponds substantially to the amount provided at an interface between the particles of the particle fluid and the host fluid.

In other words, the amount of stabiliser corresponds substantially to an amount required to coat the particles of the particle fluid thereby to form a stable nanoemulsion or nanodispersion. Thus, substantially no stabiliser is present in the host fluid at other than the interface between the particles of the particle fluid and the host fluid.

The present inventors have recognised that a problem with prior art attempts to produce nanoemulsions is that coalescence of particles formed by comminution has limited the lower bound of the size of particle that may be produced in a stable emulsion to a Sauter mean size of around 130nm. The present inventors have realised that known comminution techniques can produce particles of the dispersed phase that are below

130nm in size, however their observations indicate that such particles coalesce rapidly immediately following their formation. Rapid coalescence of the particles is believed to occur at least in part due to Van der Waals forces between particles and/or one or more other physical processes.

Ostwald ripening and/or depletion flocculation of particles may also occur since the particle size distribution is typically not uniform. Thus, larger particles may increase in size due to flocculation/coalescence of smaller particles with the larger particles.

The present inventors have also recognised that particles or molecules of stabiliser can destabilise an emulsion by a depletion flocculation process or by Van der Waals attraction. This is because in some cases the size of stabiliser particles or molecules is different to that of the particles of the particle fluid that it is desired to form. By ensuring that the amount of stabiliser present is such that the final emulsion will have substantially no stabiliser particles present in the continuous phase a more stable nanoemulsion may be created.

It is to be understood that reference to stabiliser and stabiliser particles includes reference to surfactant and surfactant micelles, molecules and aggregates thereof.

Preferably step (b) results in the formation of a medium, the method further comprising the step of

(c) subjecting the medium to a fractionation process. This feature has the advantage that particles of a size outside a prescribed size range may be removed thereby reducing a risk of excessive coarsening of particles due to van der Waals processes, Ostwald ripening, or any other deleterious coarsening process.

The mobility of a particle in a host medium is proportional to the inverse of the diameter of the particle. Thus, if a first particle has a diameter 100 times larger than a second particle, the first particle will typically move around 100 times more slowly than the second particle. Thus, small particles tend to collide with larger particles in their vicinity and become bound thereto. Removal of larger particles from a medium can therefore result in the removal of much smaller particles also. However, removal of the larger particles reduces a likelihood of coalescence of the larger particles with the smaller particles, for example during a subsequent comminution process.

Preferably the step of subjecting the medium to a fractionation process comprises the step of removing from the medium particles of a size greater than a prescribed upper size limit.

Alternatively or in addition the step of subjecting the medium to a fractionation process may comprise the step of removing from the medium particles of a size lower than a prescribed lower size limit.

The method may comprise repeating step (b) and optionally step (c). Step (b) and optionally step (c) may be repeated until the size of particles in the medium is within a prescribed range of sizes.

The step of providing a host fluid, a particle fluid to be dispersed in the host fluid and a stabiliser may comprise the step of mixing the host fluid, particle fluid and stabiliser thereby to form a premix, wherein the amount of stabiliser corresponds substantially to the amount that is to be provided at the interface between the particles of the particle fluid and the host fluid of the stable nanodispersion.

The amount of stabiliser present may be adjusted following the step of subjecting the medium to the high shear comminution process. Alternatively or in addition the amount of stabiliser in the medium may be adjusted following the step of subjecting the medium to a fractionation process.

The amount of stabiliser in the medium may be adjusted such that an amount of stabiliser in the medium corresponds substantially to the amount required to coat substantially all particles of a required final nanodispersion thereby to form the stable nanodispersion. The adjustment may be performed at any suitable stage of the process of forming the nanodispersion. Adjustment may be performed by addition or removal of stabiliser from the medium.

Filtration or any other suitable fractionation process may be used to remove stabiliser from the medium.

The step of subjecting the medium to a fractionation process may comprise the step of subjecting the particles to ultrasonic radiation.

The step of subjecting the medium to the fractionation process may be performed substantially simultaneously with the step of subjecting the medium to the high shear comminution process.

Preferably a molecular size of the stabiliser is at least five times smaller than a required size of particles of the nanoemulsion.

More preferably, a molecular size of the stabiliser is at least ten times smaller than a required size of particles of the nanoemulsion.

The present inventors have realised that rapid coalescence of particles of the dispersed phase may occur upon creation of the particles unless they are coated with stabiliser before contacting other particles. Contact with other particles may occur due for example to Brownian motion, which becomes increasingly significant as particle size decreases. It is therefore important that stabiliser molecules are delivered to fresh particle surfaces created during the comminution process as quickly as possible.

Particles of some known surfactant molecules and indeed some surfactant molecules themselves are of a size comparable with that of the nanoscale particles it is required to create. Consequently, when such particles of the dispersed phase are created, coalescence of the particles may occur before surfactant molecules have time to reach the freshly created surfaces. By ensuring that during comminution a size of stabiliser particles present is much smaller than that of the particles they are required to coat, the mobility and diffusion rate of the stabiliser may be increased. This reduces the likelihood that particles will coalesce before stabiliser molecules have had sufficient time to reach the particle surface.

Step (b) may be preceded by a step of subjecting the medium to a comminution process whereby a coarse dispersion of particles of the particle fluid having a Sauter mean diameter greater than 100 nm is formed and removing substantially all particles with a size greater than a prescribed coarse dispersion upper limit upper size limit.

Preferably the prescribed coarse dispersion upper size limit is in the range from around 100nm to around 200nm, more preferably from around 100nm to around 150nm, more preferably around 130nm.

Preferably not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially ten times that of a smallest particle of the particle fluid.

More preferably not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially five times that of a smallest particle of the particle fluid.

The method may comprise providing a mass of stabiliser M_req in the nanodispersion determined using the equation:

where p_s is the density of the stabiliser, Δr is the diameter of a portion of a head of a stabiliser molecule that is provided at the surface of a particle of particle fluid, r is half the Sauter mean average diameter of a particle of particle fluid, φ₀ is the weight percentage of particle fluid in the nanodispersion and W is the weight of the nanodispersion. In a second aspect of the invention there is provided a stable nanodispersion comprising particles of a particle fluid dispersed in a host fluid, the particles of the particle fluid having a Sauter mean diameter less than substantially 100nm.

Preferably not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially ten times that of a smallest particle of the particle fluid.

More preferably not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially five times that of a smallest particle of the particle fluid.

Preferably the nanodispersion comprises not more than substantially one particle of the particle fluid of a size greater than 10Onm per 100ml.

More preferably the nanodispersion comprises not more than substantially one particle of the particle fluid of a size greater than 100nm per 1000ml.

Preferably not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially ten times that of a smallest particle of the particle fluid.

More preferably not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially five times that of a smallest particle of the particle fluid.

Preferably the mass of stabiliser M_req present in the nanodispersion is given substantially by the equation:

where p_s is the density of the stabiliser, Δr is the diameter of a portion of a head of a stabiliser molecule that is provided at the surface of a particle of particle fluid, r is half the Sauter mean average diameter of a particle of particle fluid, φ₀ is the weight percentage of particle fluid in the nanodispersion and W is the weight of the nanodispersion.

The nanodispersion may be a nanoemulsion.

Preferably the particles of the particle medium have a Sauter mean diameter less than substantially 80nm, preferably 60nm, more preferably 50nm, still more preferably 40nm.

Preferably the nanodispersion is substantially transparent.

The nanodispersion is preferably dilutable with further host fluid.

In a third aspect of the invention there is provided a foodstuff comprising a nanodispersion according to the second aspect of the invention.

In a fourth aspect of the invention there is provided a method of stabilising a nanodispersion comprising the step of removing particles from the nanodispersion such that not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially ten times that of a smallest particle of the particle fluid.

Preferably the method comprises the step of removing particles from the nanodispersion such that not more than substantially one particle of the particle fluid per 100ml of nanodispersion, preferably 1000ml of nanodispersion, has a size greater than substantially five times that of a smallest particle of the particle fluid.

More preferably the method further comprises the step of adjusting an amount of stabiliser in the nanodispersion such that the M_req of stabiliser present in the nanodispersion is given substantially by the equation:

where p_s is the density of the stabiliser, Δr is the diameter of a portion of a head of a stabiliser molecule that is provided at the surface of a particle of particle fluid, r is half the Sauter mean average diameter of a particle of particle fluid, φ₀ is the weight percentage of particle fluid in the nanodispersion and W is the weight of the nanodispersion.

The method may comprise the step of providing the nanodispersion whereby particles of the nanodispersion have a Sauter mean diameter of less than 100nm, preferably less than 80nm, more preferably less than 50nm, still more preferably less than 40nm.

In a fifth aspect of the invention there is provided a method of forming a stable nanodispersion comprising the steps of:

(a) providing a medium in the form of a premix comprising a host fluid, a particle fluid to be dispersed in the host fluid and a stabiliser; and (b) subjecting the medium to a high shear comminution process, whereby a dispersion of particles of the particle fluid in the host fluid is formed, the particles of the particle fluid having a Sauter mean diameter of substantially 100nm or less, wherein an amount of stabiliser comprised in the medium corresponds substantially to the amount provided at an interface between the particles of the particle fluid and the host fluid.

In a sixth aspect of the invention there is provided a method of forming a nanodispersion comprising the steps of:

(a) providing a medium in the form of a premix comprising a host fluid, a particle fluid to be dispersed in the host fluid and a stabiliser;

(b) subjecting the medium to a high shear comminution process whereby a dispersion of particles of the particle fluid in the host fluid is formed, substantially all of the particles of the particle fluid being of a prescribed size, wherein the amount of stabiliser comprised in the medium is such that substantially no stabiliser molecules or particles are themselves dispersed in the host fluid.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention will now be described with reference to the accompanying figures in which: FIGURE 1 shows a flow diagram of a method of forming a nanoemulsion according to an embodiment of the invention;

FIGURE 2 is a schematic illustration of a pair of colloid particles;

FIGURE 3 shows a flow diagram of a method of forming a nanoemulsion according to an embodiment of the invention;

FIGURE 4 shows apparatus arranged to perform a fractionation process;

FIGURE 5 shows a plot of differential volume fraction as a function of emulsion droplet size for an emulsion of oil in water for Tween 20 (TM) concentrations of from 1 to 5 vol%;

FIGURE 6 is a plot of volume intensity as a function of particle size for a range of different numbers of passes of an emulsion through comminution apparatus;

FIGURE 7 is a plot of mean emulsion particle size as a function of the number of passes of the emulsion through communition apparatus showing D[3,2] (surface-diameter mean) and D[4,3] (volume-surface or Sauter mean) particle sizes;

FIGURE 8 is a schematic illustration in cross-section of an oil particle coated with surfactant molecules; and

FIGURE 9 shows a plot of calculated and actual emulsion particle sizes as a function of surfactant concentration.

DETAILED DESCRIPTION

FIG. 1 shows a flow diagram of a process of forming a nanoemulsion according to some embodiments of the invention. In the embodiment illustrated, in step S101 a premix of oil, water and stabiliser (which may be a surfactant) is first formed, for example using a Wareing blender or other suitable apparatus. Suitable oils include n-alkane mineral oils such as n-hexadecane or bromo-hexadecane, and food oils such as sunflower oil and cocoa butter. Typically the continuous or dispersing phase comprises water but any fluid in which the dispersed phase is immiscible may be used. It will be understood that such a premix is generally in the form of a relatively coarse emulsion with a particle size above 10 microns. By particle size is meant a size (typically a diameter) of a particle of a dispersed phase (such as oil) suspended in a continuous phase (such as water).

Subsequently in step S102 a high shear comminution process is applied to the premix to form an emulsion. It is to be understood that a number of different high shear comminution processes may be used for this purpose such as high-pressure homogenisation and/or ultrasound homogenisation. It is also to be understood that it is preferable to ensure that air is excluded from the process.

Immediately following the comminution process, in step S103 a fractionation process is optionally performed whereby particles having a size outside a prescribed size range are removed from the emulsion. Fractionation may be performed by ultrasound streaming, ultrasound radiation pressure, filtration through a membrane, creaming, sedimentation or any other suitable fractionation process. If creaming or sedimentation occurs it is found that in some cases it is important to remove the separated layer of the dispersed phase as quickly as possible, otherwise it may destabilise the emulsion.

The purpose of the fractionation process is to reduce a rate of coalescence or agglomeration of particles of the emulsion thereby to form a kinetically stable emulsion.

For example, van der Waals forces between particles, particularly between relatively small particles and relatively large particles may cause the small particles to couple to the large particles whereby the large particles become enlarged. The emulsion can thereby become destabilised. Eventually the small particles may coalesce into the large particles, forming a single larger particle.

This observation may explain why prior attempts to synthesize nanoemulsions have failed. Such attempts failed to exclude larger particles from the emulsions synthesized.

The present inventors have recognised that the process of enlargement of relatively large particles by the coupling of smaller particles thereto does not occur to the same degree amongst particles larger than about 200nm in the case of oil-in-water emulsions. Thus, the problem is therefore considered to be particularly acute in nanoscale emulsion systems.

As particle size decreases, the rate of coalescence of particles can increase since particle movement (Brownian motion) becomes more significant. Thus, the effects of Brownian motion and van der Waals forces can be highly problematic when seeking to synthesize a nanoemulsion or nanodispersion.

In particular, van der Waals forces become increasingly significant between small particles and much larger particles when the small particles closely approach the large particles. As the smaller particles become smaller their rate of diffusion increases. They become more likely to closely approach the larger particles when the attractive force due to van der Waals interactions becomes greater than the thermal forces that result in diffusion.

FIG. 2 is a schematic illustration of a first colloid particle 1 10 and a second colloid particle 120. The van der Waals forces between the first and second particles 1 10, 120 may be written V(R₁-R₂) where Ri represents the position of particle 1 and R₂ represents the position of particle 2. The overall van der Waals force may be determined by summing the van der Waals forces between each atom 1 12 of the first particle 1 10 and all of the atoms 122 of the second particle 120:

Where r, represents the position of atom i of particle 1 and r, represents the position of atom j of particle 2.

V(T₁-T_j) may be written:

Where O₁ represents the interaction constant for the i'th particle. In some embodiments fractionation is performed whereby particles having a diameter more than five times larger than a target particle diameter are removed from the emulsion following comminution.

By removing particles having a diameter outside this range a rate at which particles of the emulsion coalesce to form larger particles may be reduced, thus forming a more stable emulsion.

In some embodiments in which the dispersed phase and continuous phase are not density matched (i.e. they have different respective densities), fractionation may in some cases be performed by creaming or sedimentation. Thus, in the event that the density of the dispersed phase is less than that of the continuous phase, material floating to the top of the fluid following the comminution process may be removed e.g. by means of a wiping action or other method. In some embodiments the emulsion is allowed to stand for a period of time to allow floatation of undesirable particles to occur, the particles being subsequently removed. Thus embodiments of the present invention are not limited to density matched dispersed and continuous phases, nor viscosity matched phases.

For example, embodiments of the invention are suitable for use with cocoa butter dispersed in water.

In some embodiments, at step S104 it is determined whether the particle size distribution is sufficiently narrow and the particle sizes sufficiently small for the intended purpose. If not, the comminution process may be repeated (step S102) and (optionally) a further fractionation process performed (step 103). A process of comminution followed optionally by fractionation may be repeated until a required particle size distribution is obtained. In some embodiments the step of fractionation may prove necessary or desirable for the formation of a nanodispersion.

In some embodiments a size of particles of the final nanodispersion, wherein the particles are of substantially the same diameter, is determined by the amount of stabiliser present. Once substantially all of the stabiliser present is provided at an interface between the dispersed and continuous phases (and not in the form of stabiliser particles such as surfactant micelles in the continuous phase, for example) no further increase in surface area of the dispersed phase may occur since no further stabiliser is available. Thus, the amount of stabiliser present determines ultimately the particle size of the nanoemulsion or nanodispersion.

It is to be understood that the present inventors have recognised that a factor limiting the extent to which a size of the particles of an emulsion may be reduced is a time taken for stabiliser particles or molecules to diffuse through the continuous phase to a freshly created surface of the dispersed phase once the surface has been created.

For example, if stabiliser molecules do not reach a freshly created surface thereby to stabilise the surface before that surface impinges upon another freshly created surface not having stabiliser thereat, coalescence of the two freshly created surfaces is likely to occur.

Thus, in some embodiments of the invention it is important to provide a stabiliser which is sufficiently mobile to allow it to be able to diffuse to freshly created surface before such coalescence or agglomeration events can occur.

An example of a small molecule amphiphilic surfactant is caflon phcOΘO (Univar Chemicals) whose monomer is of the order of 1 nm in size and whose micelle size has not been measured, possibly because it is too small to be measured (below 5-nm). A similar size molecule which is very effective is glycerol monostearate, a food material which is nominally the stearic acid ester of glycerol but which in practice is very impure, being manufactured by esterification of glycerol with high melting point hydrogenated oils. Both these stabilizers will effectively produce a nanoemulsion.

As discussed above, the presence of particles of stabiliser molecules and in some cases individual surfactant molecules themselves can have a destabilising effect on an emulsion due to a difference in size between particles of the emulsion and micelles or individual surfactant molecules.

FIG. 3 illustrates a variation of the method of FIG. 1 in which the step of forming a premix at step S201 is followed by a comminution process at step S202 arranged to form a relatively coarse dispersion, i.e. a dispersion of particles having a diameter in excess of 100nm. Particles of a size in excess of a predetermined size are then removed in a fractionation process (step 203) before the comminution process of step S204 is performed. An advantage of the removal of such particles before the comminution process is repeated is that a rate of coalescence of particles may be reduced by reducing the range of sizes of particles passing through the comminution apparatus.

In some embodiments, after step S204 has been performed no further fractionation or comminution process is performed.

In some embodiments, following step S204 a further comminution process is performed which may or may not be followed by a further fractionation process. In some embodiments, following step S204 a further fractionation process is performed without a further comminution process being performed.

FIG. 4 shows fractionation apparatus 5 suitable for use in producing a nanodispersion according to an embodiment of the invention. The apparatus is arranged to provide a flow of a fluid 1 1 having particles 12 dispersed therein along a conduit 10. An ultrasound source 20 is arranged to subject a region of the conduit to ultrasonic radiation whereby ultrasonic waves propagate across the conduit 10. The waves create regions within which particles 12 of different respective sizes collect. In some embodiments a standing wave technique is employed in which larger particles collect at antinodes of the standing wave and smaller particles collect at nodes of the standing wave. Other arrangements and geometrical configurations are also useful.

One or more tubes 30, 40 may be provided at a location of a cross-section of the conduit 10 where particles of a required size collect. In some embodiments particles that are required to be removed from the emulsion are drawn through a tube 30, 40 and subsequently discarded. In some embodiments particles drawn through a given tube 30, 40 are intended to be kept as a constituent of the final nanodispersion, or to be kept in order to be subjected to a further comminution step.

FIG. 5 is a plot of emulsion volume fraction as a function of particle size for an emulsion having 5% by volume of oil in water for different concentrations of surfactant from 1 to 5% by volume. It can be seen from FIG. 5 that as the volume fraction of surfactant increases the mean particle size decreases. The surfactant used in this example was Tween 20 (TM). FIG. 6 shows a plot of volume intensity (%) as a function of particle size for an emulsion having 5% by volume oil in water with 2 wt% Tween 20 (TM) surfactant. Plots are shown obtained after different numbers of passes of the emulsion through a homogeniser arranged to subject the emulsion to high shear comminution.

It can be seen that as the number of passes increases, the full width at half maximum (FWHM) of the particle size distribution decreases.

FIG. 7 shows a plot of D[3,2] and D[4,3] particle sizes as a function of the number of passes of the emulsion through comminution apparatus. It can be seen that as the number of passes increases the particle size decreases.

As discussed above, the ultimate size of particles of the emulsion is determined at least in part by the concentration of surfactant molecules in the emulsion.

FIG. 8 is a schematic illustration of a cross-section of an oil particle 1 10 fully coated with surfactant molecules 120. The oil particle 1 10 has a radius r whilst the surfactant molecule has a head group of diameter Δr that is provided in contact with an outer surface of the particle 1 10.

The total volume V_h of the head groups required to fully coat the oil particle may be written:

By way of example, in the case of a caflon molecule, assuming that the volume of the molecule head group in contact with water is approximately equal to the volume of a caflon molecule:

_τ/ 4 Λr ₃ M_s

V_h =-π( — r = — 2.

3 2 A_v xp_s Where A_v is Avogadro's constant ( 6.002x10 mol ^ M_S J_S ^Q molecular weight of the surfactant used to stabilize oil droplets, and ^^s is the density of the surfactant. The molecular weight of Caflon phcOΘO is 422 g/mol and the density is 1 8 ' ^cm inserting into Equation 1 . we obtain:

TZ ⁴ A^r^ ⁴²²

6.002xl0²¹ xl.0

For Caflon phcOΘO ^Δr = 1-1x10^" cm =1.1 nm. 4.

Referring to FIG. 8, the volume of the surface layer of a single oil droplet can be calculated as:

V₅ = — π(r + Arγ TTr^ = —π[(r + Arγ - r¹]

V_s = -π(3rAr² + 3r²Δr + Δr') 3 ₆.

Since Δr j_s very small, Δr and Δr _can be neglected and therefore Equation (6.) is reduced to:

V_s = AπΔrr

For an emulsion with an average droplet radius r, the total volume of oil droplet surface layers (and therefore the volume V_req of stabilizer required to coat all the dispersed phase particles) can be calculated as:

V req = V s X - φ_o xW p₂ x—xπx r

where ^ is the weight of an emulsion, ^° is the weight percentage of oil and ^² is the density of the oil phase.

Thus, the mass of stabilizer required, M_req is given by: req r stab ^ req

where p_stab is the density of the stabilizer.

It is to be understood that the mean size of the stabilizer (which may be a surfactant as discussed above) can be determined by measuring solution density against stabiliser concentration (determined gravimetrically). This data, together with the molecular weight of the stabilizer, can be used to determine the partial molar volume of the stabilizer in solution. A formula can then be generated for the volume of the molecule depending on its shape. For example, if the molecule is approximately spherical, then the formula for the volume of a sphere can be used, if an ellipsoid, the formula for an ellipsoid and so on.

By way of example, for a 20wt% bromohexadecane-in-water emulsion with particles having an average diameter of 1 micron, if the total mass of the emulsion is 60Og and if all caflon monomers go to the oil droplet surface, the total volume of caflon phcOΘO needed is 7.92xl⁽T⁷ m³.

Since the density of caflon phcOΘO is ^{g m} , the total mass of caflon phcOΘO needed is 0.792 g. By using Equations (7.) and (8.), a change in emulsion particle size with surfactant concentration can be calculated.

The calculation can be repeated for particles of much smaller size such as particles having an average diameter of 80nm, in which case the amount of caflon phcOΘO required is significantly greater.

FIG. 9 a plot of emulsion particle size (nm) as a function of Caflon (TM) concentration showing data calculated according to the above equations (data points indicated with square indices) and data calculated from experimental results.

The calculations indicate that emulsion particle size should decrease as the surfactant concentration increases. The calculated sizes shown in FIG. 9 appear to agree with the measured sizes at intermediate surfactant concentrations. However, a discrepancy exists between measured sizes and calculated sizes at low and high surfactant concentrations.

The calculated sizes are found to be larger than the measured sizes at low surfactant concentrations. This may be because dispersed phase particles can in fact be stabilized by only partial coverage by the surfactant of the surface of the particle.

The calculated values are smaller than the measured values at high surfactant concentrations. This is because the extra surfactant molecules cause flocculation of dispersed phase particles. In other words, the surfactant molecules promote flocculation of dispersed phase particles due to the substantial difference in size between surfactant micelles and dispersed phase particles.

Reference to a stable nanoemulsion or nanodispersion is intended to include reference to nanoemulsion or nanodispersion which retains substantially the same particle size distribution for a specified period of time over a specified range of temperature. In some applications the specified period of time is a period of less than one week. In some embodiments the specified period of time is a period of up to one month, up to one year, or more than one year, for example 2 years, 3 years, 4 years, 5 years or more. In some embodiments the nandispersion is stable over a temperature range of from around 20⁰C to around 100⁰C. In some embodiments the nanodispersion is stable at temperatures up to 1000⁰C. In some embodiments the nanodispersion is stable at temperatures in excess of 1000⁰C.

In some embodiments of the invention in which a nanodispersion such as a nanoemulsion is formed, the nanodispersion is dilutable by addition of further host fluid (continuous phase). Dilution of the nanodispersion is possible without destabilisation of the nanodispersion.

Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of the words, for example "comprising" and "comprises", means "including but not limited to", and is not intended to (and does not) exclude other moieties, additives, components, integers or steps.

Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith.