Multiple Emulsions in Pharmacy

As mentioned in Chapter 12 multiple emulsions are complex systems of Emulsions of Emulsions . Two main types can be distinguished water-in-oil-in-water (W/O/W) multiple emulsions, whereby the dispersed oil droplets contain emulsified water droplets, and oil-in-water-in-oil (O/W/O) multiple emulsions, whereby the dispersed water droplets contain emulsified oil droplets. The most commonly used multiple emulsions in pharmacy are the W/O/W, which may be considered as water/water emulsions, whereby the internal water droplets are separated from the outer continuous phase by an oily layer (membrane). 

Despite the above-mentioned advantages of multiple emulsions, progress on commercial application in pharmacy has been slow for the following reasons The complex nature of the system, which may require a carefully designed two step preparation. Limited availability of surfactants that can be used in preparation of the essential two emulsions, e.g. for a W/O/W systems one has to start by preparing a W/0 emulsion, which is then further emulsified into water to produce the W/O/W drops (two surfactants with low and high HLB numbers are required). 

Lack of understanding of the factors that affect the long-term stability and that could limit the shelf-life of the product. 

One of the main instabilities of multiple emulsions is the osmotic flow of water from the internal to the external phase or vice versa. This leads to shrinkage or swelling of the internal water droplets, respectively. This process assumes the oil layer to act as a semi-permeable membrane (permeable to water but not to solute). 

The volume flow of water, /w, may be equated with the change of droplet volume with time dr/dt. 

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Besides suspensions, emulsions are dosage forms which have considerable traditional use in pharmacy. The technology of emulsions [oil-in-water (o/w) or water-in-oil (w/o)] is clearly established. In recent years, various emulsions such as water-oil in water have been developed, where water droplets are dispersed in oil droplets which are in turn dispersed in water. Such multiple emulsions may be used for prolonged oral action or intramuscular depot therapy. 

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. 

Multiple emulsions may be interesting ways for releasing bioactive compounds in a controlled rate, useful in cosmetic, pharmacy, agricultural, and industrial chemicals nevertheless, their commercial applications have been limited due to their thermodynamic instability and unexpected fast release of encapsulated bioactive molecules (Yoshida et al., 1999 Beer et al., 2013). 

In the first part of the chapter oil-in-water (O/W) emulsions will be dealt with, followed by consideration of water-in-oil (W/O) emulsions and multiple emulsions either as water-in-oil-in-water (W/O/W) or O/W/O systems. We do not intend here to deal exhaustively with emulsion stabilization, as specialist texts have recently tackled this. Carroll [1] has reviewed stability and mechanisms of emulsion breakdown, as have Vincent and Davis [2]. The literature up to 1971 was considered by Florence and Rogers [3,4] particularly in respect of non-ionic surfactant-stabilized emulsions, those that are most frequently encountered in pharmacy because of the generally lower toxicity of non-ionic surfactants. Becher s classic text [5] should still be consulted for a wealth of information on all aspects of emulsions. The aim in this chapter is to concentrate on the factors affecting the formulation and use of emulsions, especially the influence of additives, and the way the emulsion systems perform in vitro and in vivo. 

Khopade AJ, Paradkar AR, Mahadik KR. 1995. Stealth Multiple Emulsion System for passive Targeting of an Antiinflammatory Drug. International Seminar on Recent Trends in Pharmaceutical Sciences. Ootacamund, India JSS College of Pharmacy. 

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