Pharmaceutical suspensions particles flocculation

Suspensions are coarse dispersions of finely divided solids in a liquid. The solid particles have a mean particle size greater than 0.1 pm in diameter. Pharmaceutical suspensions are administered orally, topically, and parenterally and should avoid the following problems sedimentation, caking, flocculation, and particle growth. Physicochemical principles in the solid/liquid interface will be discussed in this section as they pertain to the preparation of good pharmaceutical suspensions. 

Matthews and Rhodes, Haines and Martin, Hie-stand, and Ecanow and co-workers are credited-with establishing the structured particle concept or flocculated pharmaceutical suspension. The following definitions should prove useful in avoding confusion among three closely related terms flocculation, agglomeration, and coagulation. The term aggregation can apply to all three. 

Formulation of pharmaceutical suspensions to minimise caking can be achieved by the production of flocculated systems. A flocculate, or floe, is a cluster of particles held together in a loose open stmemre a suspension consisting of particles in this state is termed flocculated (Fig. 7.27). There are various states of flocculation and deflocculation. Unfortunately flocculated systems clear rapidly and the preparation often appears unsightly, so a partially deflocculated formulation is the ideal pharmaceutical. The viscosity of a suspension is obviously affected by flocculation. 

Suspensions of liposomes, microspheres and microcapsules, and nanospheres and nanocapsules formed from a variety of polymers or proteins, as discussed in section 8.6.3 form a new class of pharmaceutical suspension in which physical stability is paramount. It is important that on injection these carrier systems do not aggregate, as this will change the effective size and the fate of the particles. The exception to this is the deliberate flocculation of latex particles administered to the eye, where aggregation leads to agglomerated... 

During extended storage, the particles in (pharmaceutical) suspensions often form agglomerates that can be no longer destroyed by shaking the preparation. This is of particular concern in, for example, eye drops. The problem can be avoided by controlled flocculation of the solids. After the addition of an electrolyte, the fine particles aggregate to loose floes that can be easily redispersed by shaking the dispenser prior to application. 

It has already been noted that pharmaceutical suspensions in which a moderate particle-panicle aggregation (flocculation) takes place are useful because the open and spongy structure of the floes makes them easily redispersible the panicles funii an irregular network with appreciable amounts uf vehicle between theht. occupying almost the whole volume of the container (Fig. fl is an example). 

The main criteria for pharmaceutical suspensions are [35-37] Colloid and physical stability, with acceptable shelf-life under storage conditions colloid stability indicates the lack of any strong irreversible flocculation. On application, any aggregates should be broken down to single particles (weak flocks are broken under shear). 

The rapid clearance of the supernatant in a flocculated system is undesirable in a pharmaceutical suspension. The use of thickeners such as tragacanth, sodium carboxymethylcellulose or bentonite hinders the movement of the particles by... 

The attractive forces between suspension particles are considered to be exclusively London-van der Waals interactions (except where interparticle bridging by long polymeric chains occurs). The repulsive forces, as discussed in Chapter 8, comprise both electrostatic repulsion and entropic and enthalpic forces. In aqueous systems the hydrophobic dispersed phase is coated with hydrophilic surfactant or polymer. As adsorption of surfactant or polymer (or, of course, both) at the solid-liquid interface alters the negative charge on the suspension particles, the adsorbed layer may not necessarily confer a repulsive effect. Ionic surfactants may neutralize the charge of the particles and result in their flocculation. The addition of electrolyte such as aluminium chloride can further complicate interpretation of results electrolyte can alter the charge on the suspension particles by specific adsorption, and can affect the solution properties of the surfactants and polymers in the formulation. Some aspects of the application of DLVO theory to pharmaceutical suspensions and the use of computer programmes to calculate interaction curves are discussed by Schneider et al. [4]. 

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

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