Emulsions liquid crystalline phases

Polar lipids form different kinds of aggregates in water, which in turn give rise to several phases, such as micellar and liquid crystalline phases. Among the latter, the lamellar phase (La) has received the far greatest attention from a pharmaceutical point of view. The lamellar phase is the origin of liposomes and helps in stabilizing oil-in-water (O/W) emulsions. The lamellar structure has also been utilized in creams. We have focused our interest on another type of liquid crystalline phase - the cubic phase... 

FIG. 11. Transmission electron micrographs of freeze fractured oily droplets dispersed (a) in a hexagonal and (b) in a cubic liquid crystalline phase, bar 100 nm. From Mueller-Goymann, C., Liquid crystals in emulsions, creams and gels, containing ethoxylated sterols as surfactant, Pharm. Res. 1 154-158 (1984). 

During the studies of phase behaviour two types of liquid crystalline phases were identified. LC material was viscous and exhibited intense "white" birefingence. material was apparently homogeneous but of low viscosity and exhibited "multi-coloured" birefringence. The liquid crystalline phases observed in the equilibrium studies of surfactant concentrations up to 25 are unlikely to take part in the self-emulsification process due to the presence of two-phase regions between L2 and liquid crystalline phases however, LC material may account for the improved stability of emulsions formed by 25 surfactant systems (Table II). Figure 4c indicates that by increasing the surfactant concentration to 30 the... 

The introduction of liquid crystals as stabilizing elements for emulsions occurred in 1969 when it was found that the sudden stabilization at emulsifier concentrations in excess of 2.5% of a water—p-xylene emulsion by a commercial octa(ethylene glycol) nonylphenyl ether was due to the formation of a liquid crystalline phase in the emulsion (26). Later investigations confirmed the strong stabilizing action of these structures (27). 

The detection of liquid crystal is based primarily on anisotropic optical properties. This means that a sample of this phase looks radiant when viewed against a light source placed between crossed polarizers. An isotropic solution is black under such conditions (Fig. 12). Optical microscopy may also detect the liquid crystal in an emulsion. The liquid crystal is conspicuous from its radiance in polarized light (Fig. 13). The structure of the liquid crystalline phase is also most easily identified by optical microscopy. Lamellar liquid crystals have a pattern of oil streaks and Maltese crosses (Fig. 14a), whereas ones with hexagonal arrays of cylinders give a different optical pattern (Fig. 14b). 

Liquid crystals stabilize in several ways. The lamellar structure leads to a strong reduction of the van der Waals forces during the coalescence step. The mathematical treatment of this problem is fairly complex (28). A diagram of the van der Waals potential (Fig. 15) illustrates the phenomenon (29). Without the liquid crystalline phase, coalescence takes place over a thin liquid film in a distance range, where the slope of the van der Waals potential is steep, ie, there is a large van der Waals force. With the liquid crystal present, coalescence takes place over a thick film and the slope of the van der Waals potential is small. In addition, the liquid crystal is highly viscous, and two droplets separated by a viscous film of liquid crystal with only a small compressive force exhibit stability against coalescence. Finally, the network of liquid crystalline leaflets (30) hinders the free mobility of the emulsion droplets. 

The final factor influencing the stability of these three-phase emulsions is probably the most important one. Small changes in emulsifier concentration lead to drastic changes in the amounts of the three phases. As an example, consider the points A to C in Figure 16. At point A, with 2% emulsifier, 49% water, and 49% aqueous phase, 50% oil and 50% aqueous phase are the only phases present. At point B the emulsifier concentration has been increased to 4%. Now the oil phase constitutes 47% of the total and the aqueous phase is reduced to 29% the remaining 24% is a liquid crystalline phase. The importance of these numbers is best perceived by a calculation of thickness of the protective layer of the emulsifier (point A) and of the liquid crystal (point B). The added surfactant, which at 2% would add a protective film of only 0.07 Xm to emulsion droplets of 5 im if all of it were adsorbed, has now been transformed to 24% of a viscous phase. This phase would form a very viscous film 0.85 Jim thick. The protective coating is more than 10 times thicker than one from the surfactant alone because the thick viscous film contains only 7% emulsifier the rest is 75% water and 18% oil. At point C, the aqueous phase has now disappeared, and the entire emulsion consists of 42.3% oil and 57.5% liquid crystalline phase. The stabilizing phase is now the principal part of the emulsion. 

These mixed-surfactant systems are used not only for their ability to form complex condensed films at the liquid-liquid interface, enhancing the stability of the emulsion, but also because of their ability to impart body to the product, resulting in a semisolid product rather than a liquid. Mixed emulsifiers control the consistency of a cream by forming a viscoelastic network throughout the continuous phase of the emulsion. The network results from the interaction of the mixed emulsifier with water, forming a liquid crystalline phase. 

In w/o emulsions the hydrocarbon chains of the adsorbed molecules protrude into the oily continuous phase. Stabilisation arises from steric repulsive forces as described in section 7.2.2. Emulsions are more complex than suspensions, because of the possibility (a) of movement of the surfactant into either the continuous or disperse phase, (b) micelle formation in both phases, and (c) the formation under suitable conditions of liquid crystalline phases between the disperse droplets. 

Emulsion stability is increased by the presence of liquid crystalline phases, as they form... 

The current state OF THE ART of various aspects of macro- and microemulsions is reflected in this volume. The symposium upon which this volume is based was organized in six sessions emphasizing major areas of research. Major topics discussed include a review of macro- and microemulsions, enhanced oil recovery, reactions in microemulsions, multiple emulsions, viscoelastic properties of surfactant solutions, liquid crystalline phases in emulsions and thin films, photochemical reactions, and kinetics of microemulsions. 

The presence of liquid crystal structures at both the w-o and o-w interfaces in multiple emulsions has been investigated by Kavaliunas and Frank (31). Microscopic examination of w/o/w emulsions between crossed polarizers revealed the presence of liquid crystal phases at both inner (w-o) and outer (o-w) interfaces in a w/o/w system composed of water, p-xylene and nonylphenol diethylene glycol ether. Liquid crystalline phases were also detected in o/w/o emulsions at both interfaces. The presence of these liquid crystal structures was found to improve the stability of the emulsions markedly. Matsumoto (32, 33) have concluded that the oil layers in w/o/w systems are likely to be composed of or contain,at least in proximity to the aqueous phase,multilamellar layers of the lipophilic surfactant used in the formulation this is postulated in part to explain the rate of volume flux of water through the oily layer. 

When surface active agents are considered, a further complication may be encountered. Because of their surface active nature, the surfactants not only emich at the surfaces, but also form extended structures themselves. At low concentrations, the surfactants remain as dissolved monomers or asssociate to oligomers. However, when the critical micellization concentration (cmc) is surpassed, a cooperative association is activated to micelles (1 to 10 nm) consisting typically of some 50 to 100 monomers. At stiU higher concentrations, or in the presence of cosurfactants (alcohols, amines, fatty acids, etc.), liquid crystalline phases may separate. These phases have an infinite order on the x-ray scale, but may remain as powders on the NMR (nuclear magnetic resonance) scale. When the lamellar liquid crystalline phase is in equilibrium with the liquid micellar phase the conditions are optimal for emulsions to form. The interface of the emulsion droplets (1 to 100 pm) are stabilized by the lamellar liquid crystal. Both the micelles and the emulsions may be of the oil in water (o/w) or water in oil (w/o) type. Obviously, substances that otherwise are insoluble in the dispersion medium may be solubilized in the micelles or emulsified in the emulsions. For a more thorough analysis, the reader is directed to pertinent references in the literature. ... 

Self-assembled microstructures of water and surfactant with or without oil have been the subject of intense research for several decades because of their rich structural variety. Microstructures ranging from spherical micelles, rod-like micelles, bicontinuous micro emulsions and liquid crystalline phases have broad commercial and scientific applications including nanomaterial synthesis, controlled delivery, coatings and detergents among many others. 

Friberg et al. (17) demonstrated that a sudden increase in emulsion stability arose in the concentration range where a liquid-crystalline phase could be separated from the emulsion. They postulated, with good reason, that this liquid-crystalline phase was the viscous layer around the emulsion droplets that Davies had been seeking. Further, the liquid-crystal stabilization hypothesis explained the difference in stability between emulsions of aromatic and aliphatic hydrocarbons, because aromatic hydrocarbons, because of their large polarizability, are more prone to form lyotropic liquid-crystal structures than aliphatic hydrocarbons. 

The presence of liquid-crystalline material at the emulsion interface has been shown by electron microscopy using the freeze-etching technique 18). Typical liquid-crystalline structures are shown in Figure 16. These liquid-crystalline compositions are viscous, and the lamellar phase displays pseudoplastic rheology. The lamellar phase is the most important of all liquid-crystalline phases for emulsion stability. The presence of a liquid-crystalline phase causes a reduction of the available London-van der Waals forces for coalescence 16). As a consequence of the reduction of the influence of these dispersion forces and the high viscosity of the liquid-crystal layer, the time for coalescence is increased dramatically. 

The formation of liquid-crystal structures also reduces the need for dispersant, because much of the liquid crystal consists of water and oil phases. A typical emulsifier concentration of about 7% is sufficient to give 40% liquid-crystalline phase in one-to-one emulsion 16). 

Surfactant molecules commonly self-assemble in water (or in oil). Even single-surfactant systems can display a quite remarkably rich variety of structures when parameters such as water content or temperature are varied. In dilute solution they form an isotropic solution phase consisting of micellar aggregates. At more concentrated surfactant-solvent systems, several isotropic and anisotropic liquid crystalline phases will be formed [2]. The phase behavior becomes even more intricate if an oil (such as an alkane or fluorinated hydrocarbon) is added to a water-surfactant binary system and the more so if other components (such as another surfactant or an alcohol) are also included [3], In such systems, emulsions, microemulsions, and lyotropic mesophases with different geometries may be formed. Indeed, the ability to form such association colloids is the feature that singles out surfactants within the broader group of amphiphiles [4]. No wonder surfactants phase behavior and microstructures have been the subject of intense and profound investigation over the course of recent decades. 

Fig. 12. Solubility and behavior at 37°C of mixtures of oleic acid (HA), sodium oleate (A ), and mono-olein (MG) the experimental design is as indicated in Fig. 11. Solid black line separates dispersions of large aggregates from dispersions of micellar size—turbid dispersions from clear dispersions. In 150 misi NaCl, fatty acid is present as oil droplets (black with white stippling) and mono-olein as a nondispersed liquid crystalline phase (horizontal hatching) or a viscous water-in-oil emulsion (cross-hatching). Increased ratios of sodium oleate result in a dispersed phase (white with black stippling), and at 10 and 15 mM sodium oleate alone is present in micellar form. In bile salt, fatty acid is also present as oil droplets (black with white stippling), and at higher concentrations mono-olein and fatty acid form a dispersed liquid crystalline phase (white with dots). In 20 mM bile salt, most of the lipid mixtures are now present in micellar solution (clear). From Hofmann (60), with the publisher s permission.

Microemulsions and surfactant-stabilized (macro) emulsions are distinctively different with respect to thermodynamic stability and, therefore, while most significant for both types of systems, the role of studies of phase behavior is different in the two cases. For emulsions we are con-eemed with two- or multi-phase regions in the phase diagrams, and for microemulsions with one-phase regions. Beeause of that micro emulsion studies are closely related to studies of other thermo-dynamically stable phases, notably liquid crystalline phases and micellar solutions. Structural models of microemulsions have to a considerable extent been advanced on the basis of our understanding of other stable phases the formation and stability of a micro-emulsion phase for a certain surfactant results from the comope-tition with alternative phases. The principal differences between micro emulsions and emulsions, together with the related nomenclature, is bound to lead to considerable confusion for example, the persistence in literature of emulsion-based structural pictures of microemulsions can be traced to the related names. However, the term microemulsions is kept for historical reasons. 

The presence of liquid-crystalline phases at the oil-water interface has been shown to produce improvements in the stability of various emulsions, although the exact mechanism of their action is still subject to some question. 

As we have seen, the stability of foams depends on a wide variety of factors involving several aspects of surface science. The potential importance of liquid crystal (LC) formation to emulsion stability was pointed out in the previous chapter. Not surprisingly, an equally important role for such structures has been identified in foaming applications. Although the phenomenon of LC stabilization of aqueous foams has been recognized for some time, their role in nonaqueous foaming systems has been less well documented. Recently, it has been shown that the presence of a liquid crystalline phase can also serve as a sufficient condition for the production of stable foams in organic systems. 

Most discussions of surfactants in solution concern themselves with relatively low concentrations so that the system contains what may be called simple surfactant species such as monomers and their basic aggregates or micelles. Before entering into a discussion of micelles, however, it is important to know that although they have been the subject of exhaustive studies and theoretical considerations, they are only one of the several states in which surfactants can exist in solution. A complete understanding of surfactants requires a knowledge of the complete spectrum of possible states of the surfactant, including liquid crystalline phases, which can be important in the stabilization of emulsions and foams, as well in other areas. 

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