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General Introduction

Several classes of formulations of disperse systems are encountered in the chemical industry, including suspensions, emulsions, suspoemulsions (mixtures of suspensions and emulsions), nanoemulsions, multiple emulsions, microemulsions, latexes, pigment formulations, and ceramics. For the rational preparation of these multiphase systems it is necessary to understand the interaction forces that occur between the particles or droplets. Control of the long-term physical stability of these formulations requires the application of various surfactants and dispersants. It is also necessary to assess and predict the stability of these systems, and this requires the application of various physical techniques.

A brief description of the various formulation types is provided in the following sections.

1.1 Suspensions

These are by far the most commonly used systems for the formulation of insoluble solids. The solid can be hydrophobic, such as most organic materials that are used in pharmaceuticals, agrochemicals, and paints; the solid can also be hydrophilic, such as silica and clays. With some pigments and inks the particles need to be very small – that is, in the nanosize range – and these are referred to as nanosuspensions. Latexes may also be considered as suspensions, particularly if the particles are solid-like at ambient temperatures. With many of the latexes that are used in paints the particles are liquid-like at below and ambient temperature, but when applied to a surface these liquid-like particles coalesce to form a uniform film. The system may then be considered as an emulsion.

For the formulation of suspensions, the hydrophobic or hydrophilic solid is dispersed in a aqueous or nonaqueous medium to produce a system that covers a wide particle size range, typically 0.1–5 μm. This process requires the presence of a surfactant (dispersant) that satisfies four criteria: (i) wetting of the powder by the liquid; (ii) the dispersion of aggregates and agglomerates into single units; (iii) comminution of the large particles into smaller units; and (iv) stabilisation of the resulting dispersion against flocculation and crystal growth. The choice of wetting/dispersing agent is crucial for achieving this control.

1.2 Latexes

As mentioned above, latexes may be considered as suspensions and are prepared using two main processes:

1. Emulsion polymerisation: In this case the monomer, for example styrene or methylmethacrylate, is emulsified in water using an appropriate surfactant. An initiator such as potassium persulphate is then added and the system is heated to produce the polymer particles. Initiation mostly occurs in the monomer swollen micelles, and the number of particles produced and their size depends on the number of micelles.
2. Dispersion polymerisation: The monomer is dissolved in a solvent in which the resulting polymer particles are insoluble. An initiator that is soluble in the solvent is added to start the polymerisation process. A protective agent that strongly adsorbs onto the particle surface (or becomes incorporated in the particle) is simultaneously added to prevent aggregation of the particles. The protective agent is a block (A-B or A-B-A) or graft (Ban) copolymer. B is the “anchor”' chain that is chosen to be insoluble in the medium and has a strong affinity to the surface, while A is the stabilising chain that is highly soluble in the medium and is strongly solvated by its molecules. This provides a strong steric repulsion.

1.3 Emulsions

These are dispersions of liquid drops in an immiscible liquid medium. The most common systems are oil-in-water (O/W) and water-in-oil (W/O). It is also possible to disperse a polar liquid into an immiscible nonpolar liquid, and vice versa; these are referred to as oil-in-oil (O/O) emulsions. In order to disperse a liquid into another immiscible liquid, a third component is needed that is referred to as the emulsifier. Emulsifiers are surface-active molecules (surfactants) that adsorb at the liquid/liquid interface, thus lowering the interfacial tension and hence the energy required for emulsification is reduced. The emulsifier plays several other roles: (i) it prevents coalescence during emulsification; (ii) it enhances the deformation and break-up of the drops into smaller units; (iii) it prevents flocculation of the emulsion by providing a repulsive barrier that prevents close approach of the droplets to prevent van der Waals attraction; (iv) it reduces or prevents Ostwald ripening (disproportionation); (v) it prevents coalescence of the drops; and (vi) it prevents phase inversion.

1.4 Suspoemulsions

These are mixture of suspensions and emulsions that can be produced by mixing two separately prepared suspensions and emulsions. Suspoemulsions may also be produced by the emulsification of an oil into a prepared suspension, or dispersing a solid an emulsion. Several instability processes may occur in these systems: (i) homoflocculation, whereby the suspension particles and emulsion drops form separate flocs; (ii) heteroflocculation, whereby the suspension particles and emulsion drops form combined flocs; and (iii) phase transfer and crystal growth. The solid particles can enter the emulsion droplets, but when they leave the droplets they may grow to form large crystals.

1.5 Multiple Emulsions

These are complex systems of emulsions of emulsions. Two types may be identified:

1. Water-in-Oil-in-Water (W/O/W), whereby the oil droplets of an O/W emulsion contain emulsified water droplets. These are generally produced via a two-step process: a W/O emulsion is first prepared using a low-hydrophilic–lipophilic-balance (HLB) which is then emulsified into an aqueous solution of a high-HLB surfactant.
2. Oil-in-Water-in-Oil (O/W/O), where an O/W emulsion that has been prepared using a high-HLB surfactant is emulsified into an oil solution of a low-HLB surfactant.

It is also possible to prepare multiple emulsions consisting of nonpolar oil droplets with emulsified polar oil droplets which are dispersed in an aqueous solution or another polar oil. With W/O/W multiple emulsions it is essential to control the osmotic balance between the internal water droplets and the external continuous phase.

Several breakdown processes may be identified with multiple emulsions:

• Expulsion of the water droplets from the multiple emulsion drop to the external phase. This may result in the production of an O/W emulsion.
• Coalescence of the water droplets in the W/O/W multiple emulsion or the oil droplets in the O/W/O system.
• Flocculation of the multiple emulsion drops that would be accompanied by an increase in the viscosity of the system.
• Coalescence of the multiple emulsion drops with the ultimate formation of a W/O emulsion.
• Diffusion of the active ingredients from the internal droplets to the external continuous phase.

1.6 Nanosuspensions

These are suspensions with a size range of 20 to 200 nm. Like suspensions, they are kinetically stable but, due to the small size of the particles, they have much longer physical stability: (i) an absence of sedimentation, as the Brownian motion is sufficient to prevent separation by gravity; and (ii) an absence of flocculation, as the repulsive forces (electrostatic and/or steric) are much larger than the weak van der Waals attraction.

Nanosuspensions can be prepared by two main process:

1. Top-up processes, whereby one starts with molecular components that can grow by a process of nucleation and growth process.
2. Bottom-down processes, whereby the large particles are subdivided by application of intense energy, for example using high-pressure homogenisers or bead milling.

The resulting nanosuspensions must be maintained colloidally stable by using surfactants and/or polymers that provide an effective energy barrier against flocculation.

1.7 Nanoemulsions

These are emulsion systems with a size range of 20 to 200 nm. Like emulsions, they are only kinetically stable but, due to the very small size, they have much longer physical stability:

• The very small droplets prevent any creaming or sedimentation, as the Brownian diffusion is sufficient to prevent separation by gravity.
• The small droplets have much smaller van der Waals attraction, and flocculation is prevented. This is particularly the case with sterically stabilised systems.
• The small droplets prevent coalescence, as surface fluctuation is not possible and the liquid film between the droplets that has an appreciable thickness prevents any thinning or disruption of that film.

The major instability process of nanoemulsions is Ostwald ripening, which results from the difference in solubility between the small and larger drops. The smaller droplets with a higher curvature have a greater solubility than the larger droplets. On storage, the droplet size distribution shifts to larger sizes and, ultimately, the nanoemulsion will become an emulsion with larger sizes. Nanoemulsions can be transparent, translucent or turbid, depending on two main parameters: the droplet size distribution and the difference in refractive index between the disperse and continuous phases.

1.8 Microemulsions

These are transparent or translucent systems covering the size range from 5 to 50 nm. Unlike emulsions and nanoemulsions (which are only kinetically stable), microemulsions are thermodynamically...