Abstract

As discussed in section 2.2 forming emulsions requires mechanical agitation to

provide energy to overcome the thermodynamic lowest energy state of the two

immiscible liquids. The work that was performed and is presented in this chapter

looked to not only emulsify liquids but to produce emulsions with a droplet size as

small as possible. Using a high-throughput platform and design of experiments

(DoE) software, both process and formulation parameters were mapped out and the

emulsions made at the most extreme conditions of the variables possible. These

emulsions were then analysed to assess the size of the droplets that made them up. A

series of algorithms were then used to predict the conditions required to make an

emulsion with the smallest possible droplet size within the limits set. These

parameters were followed, and an emulsion made, to ascertain whether within the

time-frame provided it is possible to create an emulsion with the smallest droplet size

possible. The data presented shows that, to our knowledge, an emulsion with the

smallest droplet size possible was obtained (within the parameters set for the

109 The work in this chapter has been published in:

 NanoFormulation; Riding, V., Harvey, D., Martin, P. J. and Kowalski, A. J. 2012. The Effect Of Formulation And Process Variables On Droplet Size

Reduction Using A High-Throughput Platform. Cambridge: The Royal

Society of Chemistry. p. 160

 Journal of Dispersion Science and Technology; Harvey, D. H. S., Egan, M. J. and Kowlaski, A. J. 2013. Use Of Formax High-Throughput Platform To

Create A Specific Emulsion. Journal of Dispersion Science and Technology.

34 441–543 DOI:10.1080/01932691.2012.657131

4.2 Introduction

For direct and inverse emulsions, once the immiscible liquid has been dispersed

throughout the continuous phase, it is necessary to stabilize the droplets using a

surface active agent, more commonly known as a surfactant or an emulsifier, in order

to prevent the newly formed droplets coalescing. The surfactant provides a

stabilizing repulsion between the droplet interfaces and is usually soluble within the

continuous phase (Mason et al., 2006a). When choosing which surfactant to use, the

hydrophilic-lipophilic balance (HLB) concept is commonly used (discussed in

section 2.3).

In order for droplet deformation to occur the surface and internal viscous forces must

firstly be overcome. The most common practise for this is to apply mechanical forces

to the surrounding fluid. For droplet break-up to occur the combined resistance

forces must be exceeded by the fluid forces. Elongated droplets do not always break-

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establishment of internal rotation or circulation which then helps in the stabilising of

the droplet.

Interfacial tension opposes drop deformation and in the absence of a driving force

causes the elongated droplet to regain its spherical shape. Unless critical deformation

is reached during stretching of the droplet, breakage does not occur. Should it not

occur, the droplet reverts to a condition of lower deformation as it passes to a region

of lower shear rate and the drop becomes more spherical. Collisions with solid

surfaces cause droplets to disperse through the vessel. As a result of this the

geometry of the impeller, blades, baffles, tank and vessel walls are all important for

dispersion. In stirred tanks fluid shear forces are the main cause of drop dispersion

whereas in static mixers and rotor-stator machines impingement can be of

importance (Leng and Calabrese, 2004).

For emulsions made up of significantly smaller droplets, other factors arise and

become a requirement. This is particularly important for nanoscale colloids.

Repulsive interactions between the colloids, due to excluded volume, charge on the

particles’ surfaces, or ‘steric’ interactions arising from brush-like coating of polymers on their surfaces, can effectively prevent particles from aggregating

together, and the suspension will remain homogeneous (Mason et al., 2006b).

Conversely, attractive interactions arising between structures within the dispersed

phase can arise, leading to aggregation and rapid sedimentation (Mason et al.,

2006b).

Often, it is desirable to reduce the size of the droplets within the emulsion to increase

the available surface area of a given volume of oil/water (dependent on which

111 area weighted mean, often referred to as the Sauter mean diameter, is the preferred

measurement although the D[4,3] which is the volume weighted mean, and is

conceptually similar to a sieve measurement, is also worth taking into account. The

D[3,2] value is calculated to be the ratio of the total volume of the particles to the

total surface area; thus the smaller the number, the greater the available surface area

(Phadke and Eichorst, 1991). Most commercial particle sizers will automatically

calculate these various types of mean particle size.

The definition of the adjective “nanoemulsion” has been the subject of debate amongst the academic community, with different authors quoting different ranges of

size; Mason and Meleson define a nanoemulsion as droplets that are smaller than a

100nm in size, Wang defines a nanoemulsion as being made up of droplets within

the size range of 20 to 200nm whereas Forgiarini describe an emulsion made up of

droplets within the region of 20 to 500nm in size being a nanoemulsion (Mason et

al., 2006a; Mason et al., 2006b; Meleson et al., 2004; Forgiarini et al., 2001; Wang et

al., 2007). On 31st October 2010 ISO/TS 80004-1:2010 was published and defined

the nanoscale as size range from approximately 1nm to 100nm.

Microemulsions is a term reserved for thermodynamically stable emulsions

consisting of nanodroplets, droplets with a particle size less than 100nm which

spontaneously form with very litte mechanical agitation as a consequence of a

specific combination of surfactants (Nir et al., 2010; Spernath and Aserin, 2006).

Despite the differences in opinion on a these points, all those involved in the area of

nanoemulsions agree that the function and impact nanoemulsions potentially have

for improving commercial products such as pesticides, improved drug delivery and

sterilising aids are huge (Gottenbos et al., 2002; Spernath and Aserin, 2006; Wang et

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The aim of this work was to use a combination of a high-throughput platform and

design-of-experiment (DoE) software to obtain the process and formulation

parameters required to make an emulsion with the smallest possible drop size [within

the limitations of the equipment].