Emulsifiers multiple emulsions

The term multiple emulsion describes a w/o emulsion ia an o/w emulsion. Eor example, when a w/o emulsion is added to water, no dispersion is expected unless the aqueous phase is fortified with a suitable emulsifier. The resultiag dispersioa may thea be a blead of a w/o and an o/w emulsion, or it may be a multiple emulsion of the w/o/w type. In this latter case, the initial w/o emulsion becomes the internal phase of the final product. Generally, these preparations are not very stable unless they are produced under rigidly controlled conditions (32,39,40). 

N. Garti, S. Magdassi, and D. WhitehUl Transfer Phenomena Across the Oil Phase in Water-Oil-Water Multiple Emulsions Evaluated hy Coulter Counter 1. Effect of Emulsifier 1 on Water Permeahihty. J. CoUoid Interface Sci. 104,587 (1985). 

Electrostatic and non-electrostatic biopolymer complexes can also be used as effective steric stabilizers of double (multiple) emulsions. In this type of emulsion, the droplets of one liquid are dispersed within larger droplets of a second immiscible liquid (the dispersion medium for the smaller droplets of the first liquid). In practice, it is found that the so-called direct water-in-oil-in-water (W/O/W) double emulsions are more common than inverse oil-in-water-in-oil (O/W/O) emulsions (Grigoriev and Miller, 2009). In a specific example, some W/O/W double emulsions with polyglycerol polyricinoleate (PGPR) as the primary emulsifier and WPI-polysaccharide complexes as the secondary emulsifying agent were found to be efficient storage carriers for sustained release of entrapped vitamin Bi (Benichou et al., 2002). 

Figure 7.25 Effect of the external aqueous phase pH on the release profile of vitamin Bi from multiple emulsions stabilized with WPI/xantlian gum as the external (secondary7) emulsifier ( ) pH = 7, (A) pH = 4, ( ) pH = 2. Reproduced from Benichou et al. (2004) with permission.

Figure 2.3 Optical micrograph using reflected fluorescent light showing a multiple emulsion. The continuous water phase (W, dark) shows a large dispersed oil droplet (O, bright) that contains a water droplet that also contains emulsified oil. The arrow points out an oil-in-water in oil-in-water emulsion droplet. From Mikula [66]. Copyright 1992, American Chemical Society.

Some emulsions are undesirable when they occur. In process industries chemical demulsification is commonly used to separate water from oil in order to produce a fluid suitable for further processing. The specific kind of emulsion treatment required can be highly variable, even within the same industry. The first step in systematic emulsion breaking is to characterize the emulsion in terms of its nature (O/W, W/O, or multiple emulsion), the number and nature of immiscible phases, the presence of a protective interfacial film around the droplets, and the sensitivity of the emulsifiers [295,408,451], Demulsification then involves two steps. First, there must be agglomeration or coagulation of droplets. Then, the agglomerated droplets must coalesce. Only after these two steps can complete phase separation occur. It should be realized that either step can be rate determining for the demulsification process. 

The porosity of the microspheres is apparently related to the formation of a multiple emulsion when sodium oleate was used as the emulsifier. Microscopic examination of the emulsion prior to solvent evaporation indicated that the oil droplets prepared in the presence of NaOH were comprised of numerous but very small droplets within the larger droplets which serve as precursors for the final microspheres. In contrast, oil droplets prepared in the absence of NaOH contained fewer but larger internal droplets. The pores within the final microspheres appeared to be generated by evaporation of the solvent from these internal droplets. 

No systematic studies of the use of silicone surfactants as emulsifiers have yet been published. Silicone polyoxyalkylene copolymers with relatively high molecular weight and a high proportion of silicone are effective water-in-silicone oil emulsifiers and a recent study of these copolymers suggests that they stabilize emulsions by a solid-particle mechanism [68]. This type of silicone surfactant has been used to prepare transparent water-in-oil emulsions (often with an active ingredient in the internal phase) for use as deodorants or antiperspirants as well as cosmetics and other personal care products. Their use as drug delivery vehicles has also been claimed. These copolymers can also be used to prepare multiple emulsions not requiring a two-pot process. 

Seifriz1 has produced some very interesting multiple emulsions, in which the drops of the dispersed liquid are themselves an emulsion, containing the other phase as smaller droplets inside them. In one case this multiplying process had proceeded so far that there were five kinds of drops each inside the other, three of oil and two of water Such complex phenomena may require the presence of two different emulsifying agents. 

Oil-in-water emulsions lend themselves readily to the delivery of oils and oil-soluble bioactives. The surfactant or biopolymer provides a means of isolating and protecting the lipophihc cores. Many types of materials with emulsifying capacity have been used to encapsulate oils and oil-soluble bioactives in single and multiple emulsion systems. Multilayered interfaces have also been used to improve the robustness of microcapsules. 

Lipid-based formulations of poorly water soluble drugs offer large versatility for oral administration as they can be formulated as solutions, gels, suspensions, emulsions, self-emulsifying systems, multiple emulsions, microemulsions, liposomes, and solid dispersions. " Administration of a drug in a lipidic vehicle/formu-lation can enhance the absorption and oral bioavailability via a combination of various mechanisms " " that are briefly summarized as follows ... 

A technique based on the formation of a multiple emulsion with an external aqueous phase was developed for the encapsulation of water-soluble drugs in order to replace the external oil phase. Possible unwanted interactions between the oil and the emulsified wax such as swelling or dissolution of the wax, clean-up requirements of the final product, and recovery of the oil phase could be eliminated. In analogy to the encapsulation of water-soluble drugs within polymeric microparticles by a w/o/w-solvent evaporation method, a molten wax phase was used instead of an organic polmer solution. A heated aqueous solution of pseudoephedrine HCl was emulsified into the molten carnauba wax, followed by the emulsification of this w/o-emulsion into a heated external aqueous phase. The temperature of the internal and external aqueous phases had to be kept above the melting temperature of the wax in order to avoid premature... 

Magdassi S, Frenkel M, Garti N. Correlation between nature of emulsifier and multiple emulsion stability. Drug Dev Ind Pharm 1985 11 791-798. 

Polyoxyethylene alkyl ethers are nonionic surfactants widely used in topical pharmaceutical formulations and cosmetics, primarily as emulsifying agents for water-in-oil and oil-in-water emulsions and the stabilization of microemulsions and multiple emulsions. 

Vasiljevic D, Vuleta G, Dakovic LJ, Primorac M. Influence of emulsifier concentration on the rheological behavior of w/o/w multiple emulsions. Pharmazie 1994 49 933—934. 

Double or Multiple Macroemulsions. These macroemulsions are formed by two or more than two immiscible phases which are separated by at least two emulsifier films. Multiple emulsions can also be subdivided as single emulsions in two categories (0/W/0) and (W/O/W) emulsions (14). For a 0/W/0 system, the immiscible water phase separates the two oil phases, whereas for a W/O/W system, the immiscible oil phase separates the two aqueous phases. These emulsions are schematically shown in Figure 2. 

Figure 2. Change in droplet diameter of multiple emulsions as a function of the concentration of secondary emulsifier (il) and of the calculated weighted or apparent HLB of the surfactant system. Hatched regions represent boundaries for inversion. Reprinted with permission from Ref. 28. Copyright 1979, Academic Press.

These multiple emulsions could be made by simple mixing, without any special order of addition of the ingredients. In fact, all three liquid components (the particles were previously dispersed in the respective phases) in the FC-in-toluene-in-water system were combined and emulsified simply by mixing. It is well understood that multiple emulsions are extremely process dependent and are nearly a black art. The ability to create these emulsions with minimal processing is a vast improvement over the current art. ... 

It is also possible to prepare multiple emulsions consisting of nonpolar oil droplets with emulsified polar oil droplets which are dispersed in an aqueous solution or another polar oil. With W/O/W multiple emulsions it is essential to control the osmotic balance between the internal water droplets and the external... 

Several industrial systems involve emulsions, of which the following are worthy of mention. Food emulsions include mayonnaise, salad creams, deserts, and beverages, while personal care and cosmetics emulsions include hand creams, lotions, hair sprays, and sunscreens. Agrochemical emulsions include self-emulsifiable oils that produce emulsions on dilution with water, emulsion concentrates with water as the continuous phase, and crop oil sprays. Pharmaceutical emulsions include anaesthetics (O/W emulsions), hpid emulsions, and double and multiple emulsions, while paints may involve emulsions of alkyd resins and latex. Some dry-cleaning formulations may contain water droplets emulsified in the dry cleaning oil that is necessary to remove soils and clays, while bitumen emulsions are prepared stable in their containers but coalesce to form a uniform fihn of bitumen when apphed with road chippings. In the oil industry, many crude oils (e.g.. North sea oil) contain water droplets that must be removed by coalescence followed by separation. In oil slick dispersion, the oil spilled from tankers must be emulsified and then separated, while the emulsification of waste oils is an important process for pollution control. 

All of the above processes are influenced by the nature of the two emulsifiers used to prepare the multiple emulsion. Most reports on multiple emulsions are based on conventional nonionic surfactants, but unfortunately most of these surfactant systems produce multiple emulsions with Hmited shelf-Uves, particularly if the system is subjected to large temperature variations. During the past few years, multiple emulsions have been formulated using polymeric surfactants for both the primary and multiple emulsion preparation. These polymeric surfactants proved to be superior over conventional nonionic surfactants in maintaining the physical stability of the multiple emulsion, such that today they may be applied successfully to the formulation of agrochemical multiple emulsions. The results obtained using these polymeric surfactants offer several potential applications in formulations. The key in the latter cases is to use polymeric surfactants that are approved by the FDA for pharmacy and food, by the CTA for cosmetics, and by the EPA for agrochemicals. 

The nature of the emulsifiers used for preparation of the primary and multiple emulsion. 

Emulsifier I should provide a very effective barrier against coalescence of the water droplets in the multiple emulsion drop. Emulsifier II should also provide an... 

The amount of emulsiflers used in the preparation of primary and multiple emulsion is critical. Excess emulsifier I in the oil phase may result in further emulsification of the aqueous phase into the multiple emulsion, with the ultimate production of a W/O emulsion. Excess emulsifier II in the aqueous phase may result in solubihsation of the low-H LB surfactant, with the ultimate formation of an O/W emulsion. 

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