Emulsions zeta potential

Electroultrafiltration (EUF) combines forced-flow electrophoresis (see Electroseparations,electrophoresis) with ultrafiltration to control or eliminate the gel-polarization layer (45—47). Suspended colloidal particles have electrophoretic mobilities measured by a zeta potential (see Colloids Elotation). Most naturally occurring suspensoids (eg, clay, PVC latex, and biological systems), emulsions, and protein solutes are negatively charged. Placing an electric field across an ultrafiltration membrane faciUtates transport of retained species away from the membrane surface. Thus, the retention of partially rejected solutes can be dramatically improved (see Electrodialysis). 

This energy maximum is calculated from the electric surface potential. An approximation of this surface potential is the zeta potential, which is experimentally deterrnined with commercial instmments. For o/w emulsions with low electrolyte content in the aqueous phase, a zeta potential of 40 mV is sufficient to bring the energy maximum to this level. 

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]. 

FIGURE 3. Variation of film thickness with emulsion height for different centrifugal accelerations for droplet size R = SQxlO m, surface concentration T = 5x T kglm, ionic strength m = O.lAf, thickness of adsorbed protein layer Lj = 2x (T m and zeta potential = 12mV. 

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.

Figure 7.20 Influence of salt content on properties of bilayer emulsions based on p-lactoglobulin + i-carrageenan at pH = 6.0 (a) zeta potential and (b) mean particle diameter The primary emulsion (open symbols) contained 5 wt% oil and 0.5 wt% protein die secondary emulsions (ftlled symbols) contained an additional 0.1 wt% polysaccharide. Reproduced from Gu el al. (2005b) with permission.

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. 

The first four methods are described in Refs. [81,253,254] and the electroacoustical methods in [130,255-257]. Of these, electrophoresis finds the most use in industrial practice. The electroacoustic methods are perhaps the best suited to studying concentrated suspensions and emulsions without dilution [258], In all of the electro-kinetic measurements, either liquid is made to move across a solid surface or vice versa. Thus the results can only be interpreted in terms of charge density (a) or potential (zeta potential, ) at the plane of shear. The location of the shear plane is generally not exactly known and is usually taken to be approximately equal to the potential at the Stern plane, = W d), see Figure 4.9. Several methods can be used to calculate zeta potentials [16,81,253], Some of these will be discussed here, in the context of electrophoresis results. 

Fig. 14.3 Analytical characterization of an emulsion formulation of GLA (EAS) indicates the localization of the TLR4 agonist, (a) Aqueous phase extraction followed by HPLC indicates that GLA is found in the oil phase of the emulsion, (b) A decrease in zeta potential due to incorporation of GLA in the emulsion indicates that the TLR4 agonist associates with the oil droplet interface. ES represents the emulsion alone. Reproduced with permission from Anderson et al. (2010) Coll Surf B 75, 123-132...

Wade, T., Beattie, J.K. 1997. Electroacoustic determination of size and zeta potential of fat globules in milk and cream emulsions. Coll. Surf. B. 10, 73-85. 

The author notes that his results are consistent with those of Stam-berger (27) who worked with a styrene-ethyl hexyl acrylate-acrylic acid emulsion terpolymer. At pH 8, the emulsion was stable to liquid shear, whereas at pH 3, it was unstable. There was little difference in zeta potential of the latex at the two pH values. 

Guilatt, R. L., Couvreur, P., Lambert, G., Goldstein, D., Benita, S., and Dubernet, C. (2004), Extensive surface studies help to analyse zeta potential data The case of cationic emulsions, Chem. Phys. Lipids, 131,1-13. 

Figure 13. Simplified illustration of the surface and zeta potentials for a charged emulsion droplet dispersed in high and low electrolyte concentration aqueous solutions. (Courtesy of L. A. Ravina, Zeta-Meter, Inc., Long Island...

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