Multiple emulsions preparation

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. 

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... 

Lee et al. described a promising way to prepare multiple emulsion that is derived from the emulsion inversion path (Lee et al., 2002). An oil-in-water microemulsion based on 2-butoxyethanol/n-decane/water system was mixed with oleic acid, and they observed a phase inversion sequence that includes microemulsion-in-oil to oil-in-microemulsion. 

Other methods to prepare multiple emulsions that were envisaged include the membrane emulsification technique (Higashi et al., 1995). In this method the primary OAV or W/O emulsion is formed by sonication and then filled into the upper chamber of a special apparatus (Figure 7.6). The external phase of the final multiple emulsion is continuously injected into the lower chamber... 

Ma et al. (1993) prepared multiple emulsions containing etoposide and evaluated its physicochemical properties. The release was found to be biphasic, a fast phase releasing 50% of the drug in 10 hours followed by slow phase in which up to 88% of the drug was released in next 38 hours. 

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). 

The multiple emulsion technique includes three steps 1) preparation of a primary oil-in-water emulsion in which the oil dispersed phase is constituted of CH2CI2 and the aqueous continuous phase is a mixture of 2% v/v acetic acid solution methanol (4/1, v/v) containing chitosan (1.6%) and Tween (1.6, w/v) 2) multiple emulsion formation with mineral oil (oily outer phase) containing Span 20 (2%, w/v) 3) evaporation of aqueous solvents under reduced pressure. Details can be found in various publications [208,209]. Chemical cross-linking is an option of this method enzymatic cross-linking can also be performed [210]. Physical cross-linking may take place to a certain extent if chitosan is exposed to high temperature. 

Y. Mine, M. Shimizu, and T. Nakashima Preparation and Stabilization of Simple and Multiple Emulsions Using Microporous Glass Membrane. Colloid Surfaces B Biointerfaces 6, 261 (1996). 

Kim, H.-J., Decker, E.A., McClements, D.J. (2006). Preparation of multiple emulsions based on thermodynamic incompatibility of heat-denatured whey protein and pectin solutions. Food Hydrocolloids, 20, 586-595. 

Protein-polysaccharide conjugates can also act as the stabilizers of multiple emulsions. Fechner et al. (2007) reported that, under acidic conditions, conjugate-containing water-in-oil-in-water emulsions were more stable to coalescence than the corresponding emulsions made with just sodium caseinate. They also observed that the extent of vitamin B]2 release from the inner aqueous phase of the conjugate-based system was significantly lower. This result could be useful for preparing double emulsions with variable release behaviour. 

Emulsions and suspensions are colloidal dispersions of two or more immiscible phases in which one phase (disperse or internal phase) is dispersed as droplets or particles into another phase (continuous or dispersant phase). Therefore, various types of colloidal systems can be obtained. For example, oil/water and water /oil single emulsions can be prepared, as well as so-called multiple emulsions, which involve the preliminary emulsification of two phases (e.g., w/o or o/w), followed by secondary emulsification into a third phase leading to a three-phase mixture, such as w/o/w or o/w/o. Suspensions where a solid phase is dispersed into a liquid phase can also be obtained. In this case, solid particles can be (i) microspheres, for example, spherical particles composed of various natural and synthetic materials with diameters in the micrometer range solid lipid microspheres, albumin microspheres, polymer microspheres and (ii) capsules, for example, small, coated particles loaded with a solid, a liquid, a solid-liquid dispersion or solid-gas dispersion. Aerosols, where the internal phase is constituted by a solid or a liquid phase dispersed in air as a continuous phase, represent another type of colloidal system. 

Double emulsions are also very useful for food application. Sensitive food materials and flavors can be encapsulated in w/o/w emulsions. Sensory tests have indicated that there is a significant taste difference between w/o/w emulsions and o/w emulsions containing the same ingredients, and that there is a delayed release of flavor in double emulsions [61]. W/o/w or o/w/o multiple emulsions having a concentrated aqueous-soluble flavor or a concentrated oil-soluble flavor encapsulated in the internal phase can be prepared. Food products obtained with these particulates exhibit enhanced flavor perception and extended shelf-life [62]. 

Composite emulsion as carrier of hydrophilic medicine for chemotherapy was prepared by adding albumin to the internal water phase and lecithin or cholesterol to the oil phase, thus obtaining a water-in-oil emulsion. This emulsion was then pressed through Millipore membrane into an external water phase to form a w/o/w multiple emulsion. Its advantages are high size uniformity and high storage stability [66]. 

Another field where emulsions are likely to become imperative is the production of fuel [99]. Simple and multiple emulsions represent alternative fuels for diesel engines to both increase combustion efficiency and reduce particulate emission. Considering the enormous volume of diesel that is being consumed today, a replacement of just a fraction of regular diesel by diesel emulsion could be of considerable interest to the surface chemistry community. Until now, diesel emulsions were prepared by... 

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. 

In the other procedure, Rojas et al. [215] optimized the encapsulation of BLG within PLGA microparticles prepared by the multiple emulsion solvent evaporation method. The role of the pH of the external phase and the introduction of the surfactant tween 20, in the modulation of the entrapment and release of BLG from microparticles were studied. Better encapsulation of BLG was noticed on decreasing the pH of the external phase. Addition of tween 20 increased the encapsulation efficiency of BLG and considerably reduced the burst release effect. 

Multiple emulsions can also be formed by mixing an oil-in-water emulsion with a thermodynamically incompatible biopolymer mixture. Depending on the formulation and conditions of preparation, oil-in-water-in-water or mixed oil in water/water-in-water multiple emulsions may be formed. These have potential for the controlled delivery of a range of bioactives (Kim et al. 2006). 

Liu, R., Ma, G.H., Meng, F.-T., and Su, Z.-G., Preparation of uniform-sized PLA microcapsules by combining Shirasu Porous Glass membrane emulsification technique and multiple emulsion-solvent evaporation method, J. Contrail. Ret, 103, 31, 2005. 

Herrmann, J. Bodmeier, R. Somatostatin containing biodegradable microspheres prepared by a modified solvent evaporation method based on W/O/W-multiple emulsions. Int. J. Pharm. 1995, 126 (1-2), 129-138. 

Cournarie F, Savelli MP, Rosilio V, Bretez F, et al. Insulin-loaded w/o/w multiple emulsions comparison of the performances of systems prepared with medium-chain triglycerides and fish oil. Ear J Pharm Biopharm 2004 58 477-482. 

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