The formulation of a suspension possessing optimal physical stability depends on whether the particles in suspension are to be flocculated or to remain deflocculated. First approach involves use of a structured vehicle to keep deflocculated particles in suspension; a second depends on controlled flocculation as a means of preventing cake formation. A third, a combination of first and second method, results in a product with optimum stability. The various schemes are illustrated in figure.

Dispersion of Solids

In dispersion process, the solids and water (vehicle) are in intimate contact. It is a critical and difficult step as the solids mostly are hydrophobic. Finely divided powders provide better physical stability as they adsorb a lot of air that is hard to expel. Due to this reason, the solids float on the vehicle surface, however their densities are high.

Solid dispersion in a vehicle (water) is attained by using water-miscible cosolvents and wetting agents (surfactants).

Water miscible co-solvents (alcohol, glycerine, and propylene glycol) are mainly used for hydrocolloid dispersion. In figure, the process of wetting of solids by using glycerine is summarised. Glycerine forms a coat around the solid particles and completely separates them during the mixing process.

Water is miscible with glycerine, thus it instantly surrounds the particles and wet them. This is the initial step of dispersing the solid particles. The particles are deflocculated in the vehicle at this state.

Surfactants help in the dispersion process by decreasing the interfacial tension between the solid particles and the vehicle. This reduces the contact angle and displaces the air from the solid surface. Surfactants lying in the 7-9 HLB range are used as wetting agents. Surfactants produce a large amount of foam and thus create problems during mixing; therefore should be used in a minimum amount.

Structured Vehicles – Deflocculated Suspension

Pseudoplastic or plastic rheologic behaviour are shown by the structured vehicles. These vehicles should also possess some degree of thixotropy (gelsol-gel transformation), as this increases the physical stability of suspensions. A shear thinning system obtains a gel-like structure during storage, and thus the particles do not settle down.

Viscosity reduces and the suspension becomes a sol when shaken, hence uniform dispersion of solids is achieved. Better pourability and consistent doses are given. The suspension attains back its gel-like structure when left undisturbed. Structured vehicles are used for the preparation of deflocculated suspensions.

Suspensions for oral use have non-ionic type suspending agents (in large amounts) due to the presence of high amounts of solids. Suspensions for parenteral use have suspending agents in 0.5% w/v concentration. Clays like bentonite are effective (at 2−5% w/v concentration) based upon the system pH and ionic strength. If clays are used as suspending agents, preservatives (methylparaben and propylparaben) should be added as clays stimulate moulds growth.

Density of structured vehicles is improved by adding polyvinylplyrrolidone, sugars, polyethyleneglycols (PEGs), glycerine, etc.

Controlled Flocculation – Flocculated Suspension

When the powders are suitably wetted and dispersed in a medium, flocculation occurs slowly by adding flocculating agents (electrolytes, surfactants, and polymers). The advantages of the flocs are that they do not form hard cakes and eases the re-dispersion of the sediment.

The following methods are used to attain flocculation:

1. The dispersed particles mostly carry a surface charge whose intensity is decreased by adding oppositely charged agents (e.g., electrolytes). Consequently, zeta potential is reduced and particles form attractive forces between the adjacent particles.
2. Surfactants and polymers (long chain compounds) adsorb a part of their chains on the particle surface and project out the residual part into the medium. This bridging helps in the formation of flocs.

Electrolytes

On dispersing bismuth subnitrate in water, the bismuth particles undertake a large positive charge or zeta potential (25mV or more). The like charges on the particles experience repulsive forces, thereby making the system deflocculated. Particles resist collisions even when they are brought together by agitation.

If small amount of a flocculating agent (monobasic potassium phosphate) is added in the above suspension, the negatively charged phosphate ions adsorb on the positively charged bismuth particles.

The repulsion forces reduce and the attractive forces start to operate; and consequently, the positive zeta potential reduces and the solids start forming flocs (figure).

This can be established from the maximum sedimentation volume. The zeta potential reduces and becomes zero when more electrolytes were added. In this stage also the suspended particles persist as flocs.

Dispersed particles undertake a negative charge due to excess adsorption of phosphate ions when more electrolytes were added.

Due to this, the zeta potential becomes negative, the particles again experience repulsive forces, and the suspension becomes deflocculated.

Surfactants

Surfactants enhance solid dispersion by decreasing the interfacial tension. They also work as wetting and deflocculating agents. Therefore, the surfactant concentration is of much importance for attaining flocculation.

When ionic surfactants (sodium lauryl sulphate and sodium dio-octly sulphosuccinate) are used, the head portions get adsorb on the solid surface and the tails project outwards to form bridges between the particles. This arrangement causes flocculation and stops solid precipitation (figure). Non-ionic surfactants (Tweens) also undertake a partial negative charge in aqueous dispersion and form a network between the particles.

Polymers

Polymers act as flocculating agents, thus a part of the polymer chain adsorbs on the particle surface and the remaining part projects out into the dispersion medium (figure). For example, the sedimentation volume of sulphaguanidine suspension is increased by xanthan gum (anionic heteropolysaccharide) via bridging.

Flocculation in Structured Vehicles

The supernatant in a flocculation suspension rapidly becomes clear; and this property is unwanted, therefore, a suspension with improved quality is obtained by combining the principles of flocculation and structured vehicles.

Flocculating agents assist in the formation of uniformly sized aggregates, whereas the structured vehicles inhibit the settling of aggregates. The complete process is shown in figure.

A limitation is that virtually all the structured vehicles in common use are hydrophilic colloids and carry a negative charge. This means that an incompatibility arises if the charge on the particle is originally negative. Flocculation in this instance requires the addition of a positively charged flocculating agent or ion; in the presence of such a material, the negatively charged suspending agent may coagulate and lose its suspendability.

This situation does not arise with particles that bear a positive charge, as the negative flocculating agent that the formulator must employ is compatible with the similarly charged suspending agent.