Flocculation and Coalescence

Before determining the degree of stabiUty of an emulsion and the reason for this stabiUty, the mechanisms of its destabilization should be considered. When an emulsion starts to separate, an oil layer appears on top, and an aqueous layer appears on the bottom. This separation is the final state of the destabilization of the emulsion the initial two processes are called flocculation and coalescence (Fig. 5). In flocculation, two droplets become attached to each other but are stiU separated by a thin film of the Hquid. When more droplets are added, an aggregate is formed, ia which the iadividual droplets cluster but retain the thin Hquid films between them, as ia Figure 5a. The emulsifier molecules remain at the surface of the iadividual droplets duiing this process, as iadicated ia Figure 6. 

Fig. 9 Schematic presentation of flocculation and coalescence of emulsion droplets. (From Ref. 144.)...

Phase Separation. An approximate estimation of phase separation may be obtained visually. In general, creaming, flocculation, and coalescence have occurred before phase separation is visible, thus sometimes making quantitative evaluations more difficult. Accelerating the separation by centrifugation followed by appropriate analysis of the specimens may be useful to quantitatively determine the phase separation. Details on mechanisms of creaming and phase separation as well as some advances in the monitoring techniques of emulsion stability have been reviewed by Robins [146]. 

A reduction in the electrical charge is known to increase the flocculation and coalescence rates. Sufficient high zeta potential (> — 30 mV) ensures a stable emulsion by causing repulsion of adjacent droplets. The selection of suitable surfactants can help to optimize droplet surface charges and thus enhance emulsion stability. Lipid particles with either positive or negative surface charges are more stable and are cleared from the bloodstream more rapidly than those with neutral charge [192, 193]. 

IB Ivanov, KB Danov, PA Kralchevsky. Flocculation and coalescence of micron-size emulsion droplets. Colloids Surfaces A Physicochem Eng Aspects 152 161-168, 1999. 

Example. Cream liqueurs are an example of a food emulsion for which good stability over a period of several years is required. Thus the processes of creaming, flocculation, and coalescence must all be controlled in the formulation. The product must have a cream-like appearance and a relatively high alcohol content. A possible composition might be ... 

Flocculation. Flocculation means an aggregation of emulsion droplets but, in contrast to coalescence, the films of the continuous phase between the droplets survive. Hence, the process may be partially reversible. Both processes, flocculation and coalescence, speed up the creaming of an emulsion due to the increase of the drop size. The process of flocculation is even more important for dispersions of solids than for emulsions because in this case a coalescence is not possible. 

Yamaguchi,T.,Nishizaki,K.,Itai,S.,Hayashi,H.,and Ohshima,H. (1995), Physicochemical characterization of parenteral lipid emulsion Influence of cosurfactants on flocculation and coalescence, Pharm. Res., 12,1273-1278. 

Use of Ultrasonic Vibration Potential To Monitor Coalescence. The complex chemical nature of crude oils makes it difficult to relate the dispersion behavior to the physicochemical properties at the crude-oil-water interface. In addition, the nonpolar and nontransparent nature of the oleic phase provides significant obstacles for studies of the interactions of the suspended water droplets in real systems. Recent development (28, 29) of electroacoustical techniques has shown considerable promise for electrokinetic measurements of colloidal systems and the direct monitoring of the rate and extent of coagulation (flocculation and coalescence) of water droplets in nontransparent water-in-oil media. The electroacoustic measurement for colloidal systems in nonpolar media is based on the ultrasound vibration potential (UVP) mode, which involves the applica-... 

The choice of chemical is usually based on trial-and-error procedures hence, demulsifier technology is more of an art than a science. In most cases a combination of chemicals is used in the demulsifier formulation to achieve both efficient flocculation and coalescence. The type of demulsifiers and their effect on interfacial area are among the important factors that influence the coalescence process. Time-dependent interfacial tensions have been shown to be sensitive to these factors, and the relation between time-dependent interfacial tensions and the adsorption of surfactants at the oil-aqueous interface was considered by a number of researchers (27, 31-36). From studies of the time-dependent tensions at the interface between organic solvents and aqueous solutions of different surfactants, Joos and coworkers (33—36) concluded that the adsorption process of the surfactants at the liquid-liquid interface was not only diffusion controlled but that adsorption barriers and surfactant molecule reorientation were important mecha-... 

Classical theories of emulsion stability focus on the manner in which the adsorbed emulsifier film influences the processes of flocculation and coalescence by modifying the forces between dispersed emulsion droplets. They do not consider the possibility of Ostwald ripening or creaming nor the influence that the emulsifier may have on continuous phase rheology. As two droplets approach one another, they experience strong van der Waals forces of attraction, which tend to pull them even closer together. The adsorbed emulsifier stabilizes the system by the introduction of additional repulsive forces (e.g., electrostatic or steric) that counteract the attractive van der Waals forces and prevent the close approach of droplets. Electrostatic effects are particularly important with ionic emulsifiers whereas steric effects dominate with non-ionic polymers and surfactants, and in w/o emulsions. The applications of colloid theory to emulsions stabilized by ionic and non-ionic surfactants have been reviewed as have more general aspects of the polymeric stabilization of dispersions. ... 

Shear-induced crystallization had a much greater effect in bulk systems than emulsified systems (Fig. 6) and resulted in an accelerated rate of crystallization. Prior to, and during, the initial stages of crystallization, intradroplet fat is protected from interdroplet crystallization by the spherical shape and pressure of the droplet and is not directly available to the shear field, i.e., no protruding crystals. This observation is consistent with microstructure work where limited destabilization was observed in droplets with no visible crystals. Initially, droplet interfaces in the PSCO system showed that the crystallized fat was not available at the surface, limiting the occurrence of crystal-induced flocculation and coalescence. Droplets remained stable until their interfaces were disturbed by the shear fleld or crystal interaction. 

The chapter should allow an appreciation of the factors leading to emulsion stability and physical instability, including flocculation and coalescence. Approaches to the formulation of emulsions to provide vehicles for drug delivery and parenteral nutrition (the main uses in pharmacy) should be understood. 

Flocculation and Coalescence. Flocculation being the primary process, the droplets of the dispersed phase come together to form aggregates. In this process, the droplets have not entirely lost their identity and the process can be reversible. Since the droplets are surrounded by the double layer, they experience the repulsive effect of the double layer. Kinetically, flocculation is a second order reaction since it depends in the first instance on the collision of two droplets and is expressed in the form (31)... 

Long-term stability of emulsified systems is usually provided by proteins or polysaccharides. The role of a good emulsion stabiliser is to keep the droplets apart once they have been formed. This protects the emulsion against processes such as creaming, flocculation and coalescence during long-term storage. 

Figure 10.5 Schematic representation of free energy path for breakdown (flocculation and coalescence) for systems containing an energy barrier.

For studying emulsion coalescence, it is important to consider the rate constant of flocculation and coalescence. If coalescence is the dominant factor, then the rate K follows a first-order kinetics. 

Assessment and Prediction of Creaming, Sedimentation, Flocculation, and Coalescence of Formulations... 

Flocculation and coalescence can be avoided by preventing droplets approaching each other. In fact, flocculation (which may lead to coalescence) is the result of the van der Waals forces between two droplets. These forces act at relatively short distances, and are always attractive. There are two ways to counteract these forces electrostatic repulsion and steric repulsion. 

Sjoblom J, Foredal H, Skodvin T. Flocculation and coalescence in emulsions as studied by dielectric spectroscopy. In Ref. 1 393-435. 

All parenteral emulsions are oil-in-water formulations, with the oil as the internal phase dispersed as fine droplets in an aqueous continuous phase. An emulsifier, usually egg or soy lecithin, is needed to lower the interfacial tension and prevent flocculation and coalescence of the dispersed oil phase. Mechanical energy, usually in the form of homogenization, is required to disperse the oil phase into droplets of a suitable size. For IV administration, the droplet size should be below 1 p.m to avoid the potential for emboli formation. 

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