Microemulsions thermodynamic stability

Isopar-M SSO-POEHO AIBN 1 1 > 10 50 uv Holtzscherer and Candau [3] Bkontinuous microemulsion. Thermodynamic stability Inverse- Microemulsion... 

The important properties unique to microemulsions - thermodynamic stability, ultra-low interfacial tensions, translucence, small and tunable microstructures - make microemulsions interesting for a variety of applications. Microemulsions find application as a reaction medium for formation of polymeric and inorganic nanoparticles, for the dispersion of drugs, food stuffs, agrochemicals, and cosmetic ingredients, and in detergency, the enhancement of oil recovery from reservoirs, and the extraction of contaminated solids (17). 

Emulsions are two-phase systems formed from oil and water by the dispersion of one liquid (the internal phase) into the other (the external phase) and stabilized by at least one surfactant. Microemulsion, contrary to submicron emulsion (SME) or nanoemulsion, is a term used for a thermodynamically stable system characterized by a droplet size in the low nanorange (generally less than 30 nm). Microemulsions are also two-phase systems prepared from water, oil, and surfactant, but a cosurfactant is usually needed. These systems are prepared by a spontaneous process of self-emulsification with no input of external energy. Microemulsions are better described by the bicontinuous model consisting of a system in which water and oil are separated by an interfacial layer with significantly increased interface area. Consequently, more surfactant is needed for the preparation of microemulsion (around 10% compared with 0.1% for emulsions). Therefore, the nonionic-surfactants are preferred over the more toxic ionic surfactants. Cosurfactants in microemulsions are required to achieve very low interfacial tensions that allow self-emulsification and thermodynamic stability. Moreover, cosurfactants are essential for lowering the rigidity and the viscosity of the interfacial film and are responsible for the optical transparency of microemulsions [136]. 

Microemulsions represent an intermediate state between micelles and ordinary emulsions, and it is a debatable issue whether or not they should be considered as swollen micelles rather than as small-droplet emulsions. Droplet size, though small, is nonetheless large enough to justify classification as emulsions. On the other hand, the observed thermodynamic stability and reproducibility is uncharacteristic of ordinary emulsions. 

Microemulsions are defined as isotropic, transparent, and thermodynamically stable (in contrast to conventional emulsions) mixtures of a hydrophobic phase (lipid), a hydrophilic phase (often water), a surfactant, and in many cases a co-surfactant. From a lipid formulation perspective, microemulsions are generally regarded as the ultimate extension of the decreased particle size/increased surface area mantra, because emulsion particle sizes are usually less than 50 nm. Microemulsions also have additional pharmaceutical advantages in terms of their solubilizing capacity [54, 55], thermodynamic stability, and capacity for stable, infinite dilution. 

Microemulsions, like micelles, are considered to be lyophilic, stable, colloidal dispersions. In some systems the addition of a fourth component, a co-surfactant, to an oil/water/surfactant system can cause the interfacial tension to drop to near-zero values, easily on the order of 10-3 - 10-4 mN/m, allowing spontaneous or nearly spontaneous emulsification to very small drop sizes, typically about 10-100 nm, or smaller [223]. The droplets can be so small that they scatter little light, so the emulsions appear to be transparent. Unlike coarse emulsions, microemulsions are thought to be thermodynamically stable they do not break on standing or centrifuging. The thermodynamic stability is frequently attributed to a combination of ultra-low interfacial tensions, interfacial turbulence, and possibly transient negative interfacial tensions, but this remains an area of continued research [224,225],... 

It is generally accepted that the soft-core RMs contain amounts of water equal to or less than hydration of water of the polar part of the surfactant molecules, whereas in microemulsions the water properties are close to those of the bulk water (Fendler, 1984). At relatively small water to surfactant ratios (Wo < 5), all water molecules are tightly bound to the surfactant headgroups at the soft-core reverse micelles. These water molecules have high viscosities, low mobilities, polarities which are similar to hydrocarbons, and altered pHs. The solubilization properties of these two systems should clearly be different (El Seoud, 1984). The advantage of the RMs is their thermodynamic stability and the very small scale of the microstructure 1 to 20 nm. The radii of the emulsion droplets are typically 100 nm (Fendler, 1984 El Seoud, 1984). 

Several theories have been proposed to account for the thermodynamic stability of microemulsions. The most recent theories showed that the driving force for microemulsion formation is the ultralow interfacial tension (in the region of 10 4-10 2 mN m 1). This means that the energy required for formation of the interface (the large number of small droplets) A Ay is compensated by the entropy of dispersion —TAS, which means that the free energy of formation of microemulsions AG is zero or negative. 

Micellar aggregates are considered in chapter 3 and a critical concentration is defined on the basis of a change in the shape of the size distribution of aggregates. This is followed by the examination, via a second order perturbation theory, of the phase behavior of a sterically stabilized non-aqueous colloidal dispersion containing free polymer molecules. This chapter is also concerned with the thermodynamic stability of microemulsions, which is treated via a new thermodynamic formalism. In addition, a molecular thermodynamics approach is suggested, which can predict the structural and compositional characteristics of microemulsions. Thermodynamic approaches similar to that used for microemulsions are applied to the phase transition in monolayers of insoluble surfactants and to lamellar liquid crystals. 

These results strongly suggest that a stable size does not originate from thermodynamic stability of the NiS-microemulsion supramolecules, i.e., the particles having been formed at W, are not divided into finer particles upon the alteration of W to W2 (W,< Wj). The presence of the stable size arises from kinetics origin. Furthermore, smaller particles are not redistributed to larger particles. 

The term microemulsion, which implies a close relationship to ordinary emulsions, is misleading because the microemulsion state embraces a number of different microstructures, most of which have little in common with ordinary emulsions. Although microemulsions may be composed of dispersed droplets of either oil or water, it is now accepted that they are essentially stable, single-phase swollen micellar solutions rather than unstable two-phase dispersions. Microemulsions are readily distinguished from normal emulsions by their transparency, their low viscosity, and more fundamentally their thermodynamic stability and ability to form spontaneously. The dividing line, however, between the size of a swollen micelle ( 10-140 nm) and a fine emulsion droplet ( 100-600 nm) is not well defined, although microemulsions are very labile systems and a microemulsion droplet may disappear within a fraction of a second whilst another droplet forms spontaneously elsewhere in the system. In contrast, ordinary emulsion droplets, however small, exist as individual entities until coalescence or Ostwald ripening occurs. 

It has also been shown from thermodynamic consideration (Equation 3), that if the interfacial tension is very low, the thermodynamically stable emulsions can be formed. Previous investigators (20,45,47,48) have calculated that for a situation likely to occur in microemulsion formation, the interfacial tensions would need to be in the order of 10 to 10 5 dynes/cm for thermodynamic stabilization and for spontaneous formation of microemulsions. 

One primary difference between microemulsion and macroemulsion may be drop size. The size of macroemulsion drops is generally orders of magnimde larger than the size of microemulsion drops. The difference in size explains their difference in properties and appearance however, their fundamental difference is thermodynamic stability (Bourrel and Schechter, 1988). 

Ruckenstein and Chi presented a thermodynamic treatment of a microemulsion consisting of fixed amounts of oil, water, and surfactant. The analysis yielded an optimum droplet diameter, demonstrated that the entropy of dispersion made an important contribution to microemulsion free energy, and confirmed that a very low interfacial tension of the droplets was required for thermodynamic stability. Indeed, to a first approximation, we can often estimate droplet size by taking the area per surfactant molecule as that for which interfacial tension would be zero. 

CDC are defined only by their size (most scientists agree on sizes below 1 pm others set 0.5 pm as the upper limit). CDC are very heterogeneous in all other aspects (e.g., thermodynamic stability, chemical composition, and the physical state, including solid, liquid, or liquid-crystalline dispersions) [ 1 ]. The most prominent examples are nanoparticles, nanoemulsions, nanocapsules, liposomes, nanosuspensions, (mixed) micelles, microemulsions, and cubosomes. Some CDC have reached the commercial market. Probably the best known example is the microemulsion preconcentrate of cyclosporine (Sandimmun-Neoral), which minimized the high variability of pharmacokinetics of the Sandimmun formulation. In addition, intravenous injectable CDC have been on the commercial market for many years. Examples include nanoemulsions of etomidate (Etomidat-Lipuro) and diazepam (Diazepam-Lipuro) [2-4], mixed micelles (Valium-MM, Konakion), and liposomes (AmBisome) [5]. 

Microemulsions are macroscopically isotropic mixtures of at least a hydrophilic, a hydrophobic and an amphiphilic component. Their thermodynamic stability and their nanostructure are two important characteristics that distinguish them from ordinary emulsions which are thermodynamically unstable. Microemulsions were first observed by Schulman [ 1 ] and Winsor [2] in the 1950s. While the former observed an optically transparent and thermodynamically stable mixture by adding alcohol, the latter induced a transition from a stable oil-rich to a stable water-rich mixture by varying the salinity. In 1959, Schulman et al. [3] introduced the term micro-emulsions for these mixtures which were later found to be nano-structured. 

Thermodynamic stability The thermodynamic stability of microemulsions helps in improving the shelf-life of the product making them carriers of choice. 

Use as a template to fabricate nanoparticulate systems The inherent thermodynamic stability, large interfacial area and small droplet size of the microemulsions enable them to act as a template for facile synthesis of pharmaceutical nanoparticulates systems such as solid lipid nanoparticles [11] and nanosuspensions [12]. Additionally, microemulsions represent nanoreactors which can be tailored to fabricate pharmaceutical nanomaterials. 

The 1980s were certainly a period of reaching a general consensus about one important aspect of microemulsions, namely that of thermodynamic stability. It was also a period when we obtained increasing evidence for its microstructure. It is striking that authors then normally found it important to stress what they meant by the term microemulsion . Thus, the first sentence of many papers reads like Microemulsions are thermodynamically stable fluid mixtures of water, oil, and amphiphiles/surfactants . Normally, we do not need to emphasise what we mean with a concept so this practice points to a previous confusion and a need to take a stand in a controversial issue. 

The ideas of the relevance of phase diagrams and thermodynamic stability as well as the bicontinuous structure were certainly not accepted immediately and many publications until well into the 1990s caused confusion as some authors still took droplet structures for granted. A title for a paper [31] in Nature as late as 1986 entitled Occurrence of liquid-crystalline mesophases in microemulsion dispersions illustrates both the slow acceptance and the ignorance of previous work on phase diagrams. 

Microemulsions. Unlike emulsions, microemulsions are transparent and thermodynamically stable colloidal systems, formed under certain concentrations of surfactant, water, and oil (Fig. 18.8). The transparency is because the droplet size of the microemulsions is small enough (<100 nm) that they do not reflect light. Because of its thermodynamic stability, microemulsions may have long shelf lives and spontaneously form with gentle agitation. However, microemulsions are not infinitely stable upon dilution because dilution... 

Three factors distinguish a microemulsion from an emulsion (i) the transparency, as the microemulsion is an optically isotropic solution, (ii) the thermodynamic stability of a microemulsion and the (iii) heterogeneity at the molecular level with droplets of the size 60-800 A (micelles). 

The main difference between emulsions and microemulsions lies in the size and shape of the droplets of dispersed phase, which causes the differences in the thermodynamic stability of the two systems. Emulsions allow the drug to be administered as a dispersed oil solution and thus are kinetically stable but thermodynamically unstable. After storage or aging, droplets will coalesce and the two phases separate. Unlike emulsions, microemulsions are thermodynamically stable and phases do not separate on storage. Another important difference between the two systems is their appearance emulsions have a cloudy appearance, while microemulsions are transparent because of the lower dispersed phase size than macroemulsions. 

The PIC emulsification method for preparation of microemulsions enjoys many advantages, such as low preparation cost, absence of organic solvents, good production feasibility, long stability, and thermodynamic stability." ... 

Because of thermodynamic stability, microemulsions are easy to prepare and require no significant energy contribution during preparation. Microemulsions have low viscosity compared to other emulsions. 

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