Zeta potential emulsion stability

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]. 

These stabilizers are added to the formulation in order to stabilize the emulsion formed during particle preparation. These stabilizers, however, can also influence the properties of the particles formed. The type and concentration of the stabilizer selected may affect the particle size. Being present at the boundary layer between the water phase and the organic phase during particle formation, the stabilizer can also be incorporated on the particle surface, modifying particle properties such as particle zeta potential and mucoadhesion (203). Other polymers have also been evaluated as stabilizers in earlier studies such as cellulosic derivatives methylcellu-lose (MC), hydroxyethylcellulose ( ), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC), as well as gelatin type A and B, carbomer and poloxamer (203). 

Table 7.2 Effect of the presence of an anionic polysaccharide on the measured zeta potential (Q of emulsion droplets stabilized by proteins under experimental conditions corresponding to protein-polysaccharide complexation. In all cases the complexes were formed in the bulk aqueous medium before emulsification.

There are a number of physical-chemical properties of emulsions that are important to consider when developing an emulsion formulation for a drug. These include, but are not limited to, particle (droplet) size, viscosity, osmolarity, and zeta potential, which are used to monitor the physical stability of emulsions. Assays of potency and degradant levels are used to monitor the chemical stability of emulsions. 

Physical stability. As indicated earlier, conventional emulsions are inherently unstable from a physical standpoint. Poor physical stability is ultimately exhibited by phase separation, which can be visually monitored. Certain properties of the emulsion will start to change long before this separation is visually apparent. An increase in particle size is particularly indicative of physical instability, since this monitors the coalescence or Locculation that is part of the process involved in ultimate phase separation. Increases in viscosity (due to Locculation) and changes in zeta potential (arising from a decrease in droplet surface area) are both indicative of poor physical stability. The presence of drug and cosolvents can potentially hasten the phase separation. 

Electrokinetics. Bottle tests and centrifugation may be somewhat crude, but they do offer a relative measure of emulsion stability that combines, to some extent, all of the factors that affect stability. Electrokinetic measurements are somewhat more elegant because they allow direct measurement of the degree of electrostatic stability in an emulsion system. The zeta potential, or relative magnitude of the electric charge on the surface, is... 

Figure 11. Schematic representation of the electrophoretic mobility (A) measurement showing the major components. In an applied electric field, emulsion droplets move according to their surface charge. These charges can electrostatically stabilize an emulsion system by preventing the droplets from coming into contact and coalescing. The motion of the droplets is visually observed, and the electrophoretic mobilities of a number of particles are measured to determine zeta potential. The sedimentation potential (B) is also illustrated.

Emulsions have been widely used as vehicles for oral, topical, and parenteral delivery of medications. Although the product attributes of an emulsion dosage form are dependent on the route of administration, a common concern is the physical stability of the system, in particular the coalescence of its dispersed phase and the consequent alteration in its particle-size distribution and phase separation. The stabilization mechanism(s) for an emulsion is mainly dependent on the chemical composition of the surfactant used. Electrostatic stabilization as described by DLVO theory plays an important role in emulsions (0/W) containing ionic surfactants. For 0/W emulsions with low electrolyte content in the aqueous phase, a zeta potential of 30 mV is found to be sufficient to establish an energy maximum (energy barrier) to ensure emulsion stability. For emulsions containing... 

A relative wealth of information relating to the application of zeta potential to injectable emulsions has been documented with respect to the use of total nutrient admixtures (TNA). Total nutrient admixtures are prepared by mixing the lipid emulsion with other components (i.e., dextrose, amino acids, and electrolytes) in a single container prior to administration. Depending on composition, the mixtures vary widely in their stability and may show clinically unacceptable coalescence after different periods of storage time. 

When the electrostatic stabilization of the emulsion is considered, the electrolytes (monovalent and divalent) added to the mixture are the major destabilizing species. The zeta potential of the emulsion particles is a function of the concentration and type of electrolytes present. Two types of emulsion particle-electrolyte (ions) interaction are proposed non-specific and specific adsorption.f H non-specific adsorption the ions are bound to the emulsion particle only by electrical double-layer interactions with the charged surface. As the electrolyte concentration is increased, the zeta potential asymptotes to zero. As the electrostatic repulsion decreases, a point can be found where the attractive van der Waals force is equal to the repulsive electrostatic force and flocculation of the emulsion occurs (Fig. 9A). This point is called the critical flocculation concentration (CFC). 

The addition of electrolyte or dmgs to intravenous fat emulsions is generally contraindicated because of the risk of destabilising the emulsion. Addition of cationic local anaesthetics reduces the electrophoretic mobility of the dispersed fat globules, and this contributes to instability. Minimum stability (and minimum zeta potential) is caused by addition to Intralipid of 3 x 10 mol dm CaCl2 and 2.5 X 10 mol dm NaCl, which are thus... 

The charge on emulsion stabilized by sulpha-pyridine was found to be negative. The electrokinetic mobility of the emulsion was measured and the zeta potential was calculated by the Helmholtz equation,... 

The present paper deals with kinetics of coagulation of Phthallylsulfathiazole stabilized xylene in water emulsion in the presence of some cationic detergents. Rate of flocculation, rate of coalescence and rate of creaming have been determined. To estimate the stability of the present systems their zeta potentials have been measured and stability factors calculated. Temperature effect on the system was also studied. 

The overall results show that electrostatic factors lead to the formation of first black films from non-ionic surface active agents in electrolytes and that zeta-potentials as low as 18 mV are adequate to stabilize the film assuming the film potentials are comparable with those of the emulsion drop. As shown in more detail elsewhere, the DLVO theory can be used... 

Multiple regression analysis performed for succinylated rapeseed protein isolates indicated that emulsification activity was related to protein solubility, hydrophobicity, zeta potential, and flow behavior of aqueous dispersions of the proteins. Emulsion stability was affected by protein solubility, zeta potential, apparent viscosity of protein dispersions, and difference in density between aqueous and oil phases [76],... 

---