Diffusion in Emulsions and Emulsion Mixtures

Alliance Pharmaceutical Corp., 3040 Science Park Road, San Diego, California 92121, USA 

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Weers J. G. 1998. Molecular diffusion in emulsions and emulsion mixtures. In Modem Aspects of Emulsion Science, Chapter 9, pp. 292-327. B. P. Binks (ed.). The Royal Society of Chemistry, Cambridge, U.K. 

The United States Food and Drug Administration issued a safety alert in 1994 regarding the potentially life-threatening formation of precipitates in parenteral nutrition admixtures (148). They had received reports of two deaths and at least two cases of respiratory distress during intravenous infusion of a three-in-one parenteral nutrition mixture (amino acids, carbohydrates, lipids). The mixture contained 10% FreAmine III (amino acids -I- magnesium acetate -I- phosphoric acid -I- potassium chloride -I- sodium acetate -I- sodium chloride), dextrose, calcium gluconate, potassium phosphate, other minerals, and a lipid emulsion. The solution may have contained a precipitate of calcium phosphate. Autopsies revealed diffuse microvascular pulmonary emboli containing calcium phosphate. 

Many dithiocarbamate complexes of zinc, silver, cadmium or mercury improve emulsion stability, including bis(dibenzyldithiocarbamato)-zinc(II) or -cadmium(II) and silver(I) diethyldi-thiocarbamate. Cadmium salts, mixed with citric acid or tartaric acid and added to the emulsion, are reported to be effective. Mercury(II) complexes of ethylenediaminetetraacetic acid (EDTA) and related ligands and of solubilized thiols such as (4) can be used. Other coordination compounds reported include EDTA and related ligand complexes of Co and Mn, mixtures of Co salts with penicillamine (5) and macrocyclic complexes of Ag such as (6). The latter compounds may be used in diffusion transfer systems in which transferred maximum densities are stabilized. 

Emulsions are formed by mixing two liquids, a process which creates discrete droplets in a continuous phase. During emulsification,by mechanical agitation for example, both liquids tend to form droplets resulting in a complex mixture of 0/W and W/0 emulsions. Which of the components forms the continuous phase depends on the emulsifier used since one of the types of droplet is unstable and coalesces. Therefore, there is a need to identify the continuous phase in emulsion systems not only in the final emulsion system, but also at short times after emulsion formation or even dining the emulsification process. The NMR self-diffusion method may easily distinguish the continuous and... 

Emulsion polymerization is similar to suspension polymerization in the sense that the reaction also takes place in the presence of a water phase and the applied monomer forms a second liquid phase. However, in this case the added radical initiator is not soluble in the monomer droplets but in the water phase. To allow the monomer to come into contact with the initiator an emulsifier is added to the reaction mixture that creates micelles in the systems. By diffusion processes both monomer molecules and initiator molecules reach the micelle. Polymerization takes places and a polymer particle suspended in the water phase forms that is much smaller than the original monomer droplet (see Figure 5.3.12 for a graphical illustration of these steps). At the end of the overall emulsion polymerization process, all monomer droplets have been consumed by the polymerization reaction in the micelles. Typical emulsifiers for emulsion polymerization are natural or synthetic detergents, such as, for example, sodium palmitate or sodium alkyl sulfonates. Emulsion polymerization is very versatile and is applied for many polymers [e.g., PVC, styrene copolymers, poly(methacryl esters)] in batch, semi-continuous, and continuous processes. In some cases, the obtained polymer particles in water are directly applied as technical products for coatings, lacquer applications, or as adhesives. In other cases the formed product is further treated to obtain the dry polymer. Note that the aqueous phase in emulsion polymerization always contains some isolated emulsifier and also some monomer. Moreover, the formed polymer contains the emulsifier as impurity. 

Optical fibres can be used in the transmittance and ATR mode (a special ATR application is the remote sensor), and even in the reflectance mode. The development of special optical fibres for transmission, transflection or diffuse reflectance measurements favours on-line analysis of problematic product streams and reaction mixtures (solutions, suspensions, emulsions, melts, solids). Both quartz and fluoride (ZrF4-based) glass fibres are used, with the former having poor transmission characteristics above 2000 nm. 

The relatively large monomer droplets (generally 2-5ym in diameter) have too small a surface area to capture radicals from the aqueous phase and therefore serve as reservoirs for the diffusion of monomer through the aqueous phase to the pol3onerizing oligomeric radicals, micelles, or polymer particles. Despite the unfavorable statistical probabilities, however, some monomer droplets capture radicals and polymerize to form microscopic or near-microscopic particles (14), and some of these particles which are entirely separate from the main particle size distribution are formed in most batch polymerizations. Polymerization in monomer droplets becomes much more significant when the size of the emulsion droplets is decreased. The use of ionic emulsifier-fatty alcohol mixtures (13) and, later, ionic emulsifier-alkane mixtures (15), allows the preparation of 0.1-0.2ym size styrene monomer droplets, which compete favorably with initiation in micelles and in the aqueous phase as the mechanism of particle nucleation. The mechanism of formation of these "mini-emulsions" has been attributed to the very low solubility of the fatty alcohols and alkanes in water (16) or to the formation of crystalline complexes between the ionic emulsifiers and fatty alcohols (17) the two mechanisms are not mutually exclusive. Thus this mechanism pertains only to special systems. 

Experiments confirm the decrease in the ripening rate on addition of a poorly soluble component to the dispersed phase. Buscall et alP examined emulsions of SDS after adding long chain alkanes. Kabal nov et al showed that eqn. (1.22) was well obeyed for emulsions of SDS and hexane to which small quantities of the alkanes octane to hexadecane were added. Recently, Weers and Arlauskas have provided the first experimental evidence that molecular diffusion in two-component mixtures leads to an increase in the mole fraction of the less soluble component in the smaller drops. Using the technique of sedimentation field-flow fractionation coupled with gas chromatography, the disperse phase composition can be determined for monosized drop fractions. Evidence is also provided for the development of bimodal distributions at low volume fractions of the less soluble component, in excellent agreement with the above predictions. Their system was perfluorooctyl bromide (plus perfluorododecyl bromide) as oil stabilised by egg yolk phospho-lipid.2 ... 

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