Flocculated suspensions:

Flocculation: It refers to the formation of a loose aggregation of discrete particles held together in a net-work like structure either by physical adsorption of macromolecules, bridging during chemical interaction or when the longer range Van-der Waal’s forces of attraction exceed the shorter range forces of repulsion.

Agglomeration: Here a large number of particles, a mass, are closely bound together as aggregates either in a dry or liquid state.

Coagulation (severe over flocculation): It refers to massing of particles in a liquid state alone and sometimes in the form of a fluid gel structure. The solubility rate of unprotected, nucleated particles is greater than that of the large crystals, dissolution of smaller particles creates a temporary or metastable state of saturation, which causes eventual growth from solution onto the proper crystal edge of large particles until a new, more thermodynamically stable distribution of particle sizes is achieved. This phenomenon tends to promote ‘caking or cementing’ together of particles. The creation of a protective coat or boundary layer with a hydrophilic colloid about such particles offers the best protection to crystal growth.
According to the above figure, the flocculated stable state (C) may be reached either directly by wetting and dispersing hydrophobic particles (A) with a suitable flocculating surfactant or indirectly by first wetting and dispersing to produce a dispersed or peptized particle (B) with a suitable surfactant and then flocculating with a suitable agent such as a hydrophilic colloid or polyelectrolyte. Good pharmaceutical suspensions are best achieved through the formation of a stable floc, which resists the tendency toward either deflocculation or agglomeration.

The chief advantages of the stable floc are as follows –
The aggregates tend to break up easily under the application of small amounts of shear stress, such as gentle agitation of a bottle or vial or by the flow through a small orifice and reform an extended network of particles after the force is removed.
The stable floc will settle rapidly, usually to a high sediment volume, and may be easily resuspended even after standing for prolonged periods of storage.
The stable floc can be produced by employing aseptic techniques that are safe for intramuscular injection.

There are several methods of producing flocculated pharmaceutical suspensions. The choice of method depends on the properties of the drug and the class of suspension desired. The following example illustrates how suspensions may be prepared by controlled flocculation procedures.
The weting agent, polysorbate (not more than 0.1-0.2%w/v of the final conc) is dissolved thoroughly in approximately half the final volume of aqueous vehicle. An anionic surfactant such as docusate Na USP may also be used as a wetting agent. In case of hydrophilic solids, a wetting agent is usually not required.
Ultrafine [articles of the drug at the desired final concentration are uniformly and carefully spread over the surface of the vehicle ad the drug is permitted to wet undistributed for as much as 16hr.
The wetted slurry is passed a very fine wir mesh screen (120mesh of larger) to remove poorly wetted powder. Alternatevly a colloid mill can be used to achieve the same result.

The slurry concentrate of the drug is agitated gently using an impeller type mixer.
Small amounts of a 10% w/v solution of aluminum chloride hexahydrate are then added drop-wise to the drug slurry from a burette or dropping pipette until the flocculation end point is reached.
After the flocculation end point has been established and verified, the rest of the suspension components dissolved in the liquid vehicle are added and the slurry is brought to final volume with liquid vehicle.