Surfactants cosurfactants

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

Eigure 6 illustrates how the three tensions among the top, middle, and bottom phases depend on temperature for a system of nonionic surfactant—oil—water (38), or on salinity for a representative system of anionic surfactant—cosurfactant—oil—water and electrolyte (39). As T approaches from lower temperatures, the composition of M approaches the composition of T, and the iaterfacial teasioa betweea them, goes to 2ero at T =. ... 

Various initiation strategies and surfactant/cosurfactant systems have been used. Early work involved in situ alkoxyamine formation with either oil soluble (BPO) or water soluble initiators (persulfate) and traditional surfactant and hydrophobic cosurfactants. Later work established that preformed polymer could perform the role of the cosurfactant and surfactant-free systems with persulfate initiation were also developed, l90 222,2i3 Oil soluble (PS capped with TEMPO,221 111,224 PBA capped with 89) and water soluble alkoxyamines (110, sodium salt""4) have also been used as initiators. Addition of ascorbic acid, which reduces the nitroxide which exits the particles to the corresponding hydroxylamine, gave enhanced rates and improved conversions in miniemulsion polymerization with TEMPO.225 Ascorbic acid is localized in the aqueous phase by solubility. 

A microemulsion droplet is a multicomponent system containing oil, surfactant, cosurfactant, and probably water therefore there may be considerable variation in size and shape depending upon the overall composition. The packing constraints which dictate size and shape of normal micelles (Section 1) should be relaxed in microemulsions because of the presence of cosurfactant and oil. However, it is possible to draw analogies between the behavior of micelles and microemulsion droplets, at least in the more aqueous media. 

A microemulsion is defined as a thermodynamically stable and clear isotropic mixture of water-oil-surfactant-cosurfactant (in most systems, it is a mixture of short-chain alcohols). The cosurfactant is the fourth component, which effects the formation of very small aggregates or drops that make the microemulsion almost clear. 

Microemulsions are thermodynamically stable mixtures. The interfacial tension is almost zero. The size of drops is very small, and this makes the microemulsions look clear. It has been suggested that microemulsion may consists of bicontinuous structures, which sounds more plausible in these four-component microemulsion systems. It has also been suggested that microemulsion may be compared to swollen micelles (i.e., if one solubilizes oil in micelles). In such isotropic mixtures, short-range order exists between droplets. As found from extensive experiments, not all mixtures of water-oil-surfactant-cosurfactant produce a microemulsion. This has led to studies that have attempted to predict the molecular relationship. 

Czuryszkiewicz T, Rosenholm J, Kleitz F, Linden M (2002) Synthesis and characterization of mesoscopically ordered surfactant/cosurfactant templated metal oxides. Impact of Zeolites and Other Porous Materials on the New Technologies at the Beginning of the New Millennium, Book Series Studies in Surface Science and Catalysis, Pts A and B 142 1117-1124... 

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]. 

The preferred method of delivery of oral microemulsion formulations is either as a combination of drug, lipid, and surfactant/cosurfactant (generally filled into soft or sealed hard gelatin capsules) that spontaneously microemulsify in the GIT, or as a microemulsion preconcentrate in which the dose form contains a small quantity of hydrophilic phase and is in itself a concentrated O/W or W/O microemulsion, which becomes diluted or phase inverted in the GI fluids. 

Finally, one word about the lattice theories of microemulsions [30 36]. In these models the space is divided into cells in which either water or oil can be found. This reduces the problepi to a kind of lattice gas, for which there is a rich literature in statistical mechanics that could be extended to microemulsions. A predictive treatment of both droplet and bicontinuous microemulsions was developed recently by Nagarajan and Ruckenstein [37], which, in contrast to the previous theoretical approaches, takes into account the molecular structures of the surfactant, cosurfactant, and hydrocarbon molecules. The treatment is similar to that employed by Nagarajan and Ruckenstein for solubilization [38]. 

From the point of view of traditional thermodynamics, a microemulsion is a multicomponent mixture formed of oil, water, surfactant, cosurfactant, and electrolyte. There is, however, a major difference between a conventional mixture and a microemulsion. In the former case, the components are mixed on a molecular scale, while in the latter, oil or water is dispersed as globules on the order of 10-100 nm in diameter in water or oil. The surfactant and cosurfactant are mostly located at the interface between the two phases but are also distributed at equilibrium between the two media. In conventional mixtures, the sizes of the component species are fixed. In the case of microemulsions, the sizes of the globules are not given but are provided by the condition of thermodynamic equilibrium. 

The prediction of r and as a function of the natures of surfactant, cosurfactant, and hydrophobic phase requires the derivation of expressions for y and C that should account for, among other things, their dependence on the curvature. Such expressions are not yet available. 

In the second part of the paper, it will be shown that the partition of the alcohol between the phases can explain the deviations from the ideal dilution law for a water/ oil/surfactant/cosurfactant lyotropic lamellar liquid crystal. 

In Figure 6 the repeat distance (Figure 6a) and the thickness of the oil lamellae (Figure 6b) are plotted as functions of

total volume), for fixed volume... 

Fig. 11. Relative phase volume-corrected rate constants vs weight fraction water for the io-dosobenzoate-catalysed hydrolysis of a phosphate ester in water/hexadecane microemulsions stabilized by various surfactant/cosurfactant mixtures. Curve (a) Brij 96/1-butanol curve (b) CTAB/I-butanol curve (c) CTAC/dibutylformamide curve (d) CTAB/2-methylpyrrolidone and Adogen 464 (from [26])...

Viscosity studies have also been carried out to investigate the effect of the surfactant and cosurfactant concentrations as well as the surfactant-cosurfactant mass ratio on the hydration of the disperse-phase droplets for o/w ME systems [58], A... 

One major concern regarding the safety profile of ME systems intended for oral administration is the comparatively high amphiphile content. Both o/w and w/o ME systems are amphiphile-rich systems compared to conventional emulsions and would contain in the most conservative case up to 15-20% w/w surfactant-cosurfactant. This is further complicated by the limited models available to evaluate chronic toxicology in comparison to conventional oral dosage forms such as tablets [91]. 

SURFACTANT SURFACTANT COSURFACTANT (SIMPLE FUNCTIONAL) HYDROCARBON... 

Figure 3. Microemulsion catalysis a, reaction at an interphase b, reaction after transport across the interphase. Key , water soluble ion , water /vws, oil phase molecules , polar organic reactant 9-, surfactant cosurfactant and---------------------------------------------------------, nonpolar organic reactant.

In particular, contacting studies where two phases of varied constituents (surfactant, cosurfactant, oil, water, electrolyte) are in contact and results interpreted on the basis of mass transfer and phase diagrams have become the standard method for studying transport in such systems (10-18). 

The diffusion experiments for the nonsalt compositions (Fig. IE) showed a fast equilibration of the surfactant concentration with equal concentration of surfactant in the entire system after 30 days at the lowest surfactant/(cosurfactant + surfactant) weight ratio, 0.14, Fig. 2A. Thereafter the concentration in the lower part was higher than in the upper part, a fact that is to be viewed against the former low cosurfactant concentration. Fig. 2B, and its high water content. Fig. 2C. The increase in water content in the upper layers ceased after 20 days. Fig. 2C, at the time when the liquid crystal began to form in layer 6, Fig. 3. During the first 7 days the aqueous solution was turbid and an interface appeared within the oil phase. Fig. 3. This interface moved upwards in the oil phase and disappeared after 36 days. 

With increased surfactant/(cosurfactant + surfactant) ratio (0.22), the liquid crystal was formed immediately and the interface in the oil layer now lasted only 12 days, (Fig. 4). The formation of a liquid crystal impeded the transport of surfactant to the lower part. Fig. 5A. In this case, the surfactant concentration remained lower in the bottom layers during the entire duration of the experiment more than 2 months. The transport of cosurfactant to lower parts. Fig. 5B, and water from the layers below the liquid crystal. Fig. 5C, were not influenced to a great degree by the enhanced amount of liquid crystal. 

For the highest surfactant/(cosurfactant + surfactant) ratio (0.35), the liquid crystal also formed early. Fig. 6, in layers 5 and 6. This resulted in the concentration changes being focused towards the bottom layers the higher reservoir of surfactant and cosurfactant in the top layers resulted in small changes of their concentrations, Figs. 7A-C. The slowest process was the disappearance of the birefringence a time of 9 months was needed for that to happen. Fig. 6. 

For the 1 M NaCl system the solubility region was further reduced. Fig. 13, and the water solubilization maximum found at even higher surfactant/cosurfactant ratio. The series with the lower ratios of surfactant to cosurfactant showed an uptake of the aqueous solution somewhat similar to the series in the system with 0.5 M NaCl. The series with the surfactant/(cosurfactant + surfactant) ratio equal to 0.4 gave an initial liquid crystal formation lasting for 2-3 days folllowed by a middle phase lasting a longer time. The liquid crystalline and the middle phase layer were both more pronounced for the sample with initial salt concentration equal in the water and in the microemulsion. Fig. 14A, than for the sample with all the salt in the water. Fig. 14B. 

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