Multiple emulsions stability

Stable double emulsions, based on various block copolymers of polyethylene oxides and polypropylene oxides known as Pluronies, have been used. In a recent example. Cole and Whateley (84) have used complexes of Pluronic F127 PAA (polyaerylie aeid) in the internal aqueous phase. In the oil phase, Span 80 and Pluronie LlOl (5 wt %) were used. The outer interfaee was stabilized by xanthan gum (0.25 wt %) and Tween 80 (1 wt %). Theophylline and I-insulin (iodinated insulin) were ineorporated in the internal aqueous phase of the stabilized multiple emulsion, and the release rates were studied. The release rates were found to be related to the droplet sizes of the emulsion whieh were dependent on the partiele size of the pluronie F127 PAA eomplex in the internal aqueous phase and the type of the lipophilie surfaetant in the oil phase. The authors have used the eomplex between the poloxamer surfactant and PAA that occurred at pH 2 and at low molar ratio as a barrier for the release of active matter from the inner to the outer phase. 

Numerous applications of multiple emulsions in various fields have been reported. More applications need to be realized if multiple emulsions stability is to be fully understood and approaches to stabilize multiple emulsions fully rationalized. The stability of multiple emulsions is influenced by numerous formulation and process variables. As demonstrated in this chapter, long-term multiple emulsion stability is dependent on the osmotic and Laplace pressures of the inner droplets as well as on the pressure balance between them described by the Walstra equation. Stability also equally, in some cases even more, depends on the strength of the interfacial film formed on the interface of droplets of multiple emulsions. This property can be characterized by interfacial rheology. 

BIOPOLYMER AS STABILIZED MULTIPLE EMULSIONS 105 TABLE 5.2 Multiple emulsion stability after storage for 20 days, at 4°C, 20°C, and 40°C... 

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). 

Slow release rates and remarkable long shelf-life (months) were obtained compared to typical multiple emulsions stabilized by two short surfactants (SMO and polyoxyethylene (20) sorbitan monolaurate). Finally, the long lifetime of the emulsions allowed study via diffusing wave spectroscopy (DWS) of the interactions between the droplets and the globule surface [37],... 

Y. Sela, Y. Magdassi, and N. Garti Polymeric Surfactants Based on PolysUoxanes-Graft-Poly(Oxyethylene) for Stabilization of Multiple Emulsions. Colloids Surfaces 83, 143 (1993). 

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.

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. 

Other drug-delivery systems may include double emulsions, usually W/O/W, for transporting hydrophilic dmgs such as vaccines, vitamins, enzymes, hormones [441], The multiple emulsion also allows for slow release of the delivered drug and the time-release mechanism can be varied by adjusting the emulsion stability. Conversely, in detoxification (overdose) treatments, the active substance migrates from the outside to the inner phase. 

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]. 

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. 

Over the years there have been many attempts to find systemic methods for screening potential emulsifiers from the enormous number of surfactants available commercially. Although the mechanisms governing the stability of emulsions, including the complex multiple... 

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. 

Emulsions - liquid dispersions usually of an oil phase and an aqueous phase - are a traditional pharmaceutical dosage form. Oil-inwater systems have enjoyed a renaissance as vehicles for the delivery of lipid-soluble dmgs (e.g. propofol). Their use as a dosage form necessitates an understanding of the factors governing the formulation and stability of oil-in-water (o/w) and water-in-oil (w/o) emulsions, multiple emulsions (w/o/w or o/w/o) and microemulsions, which occupy a position between swollen micelles and emulsions with very small globule sizes. Photomicrographs of o/w, w/o systems and multiple emulsions are shown in Fig. 7.10. It is also possible to formulate nonaqueous or anhydrous emulsions, that is oil-in-oil systems and even multiple oil-in-oil-in-oil systems. 

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