Microemulsions formulation

Many surfactants have been used to formulate microemulsions (1). They were of three types anionic surfactants such as petroleum sulfonates, sodium octyl benzene sulfonate, sodium dodecyl sulfate, alkaline soaps cationic surfactants such as dodecyl ammonium and hexadecyl eimmonium chlorides or bromides and nonionic surfactants such as polyoxyethylene glycols. Furthermore, many exhibit liquid-crystalline properties (2) and in some cases the structure of the mesophases has been established (3). Nevertheless, nearly nothing is known about their compatibility with blood and tissues, and, from our own experience, some exhibit a high lytic power for red cells... 

These are transparent isotropic structured fluids composed of two immiscible phases that are stabilized by surfactants. Often a co-surfactant and a co-solvent are present in the formulation. Microemulsions form spontaneously and are thermodynamically stable. Their transparency is due to the small droplet size (<100 nm) in microemulsions (Flanagan and Singh, 2006 Garti and Aserin, 2007). 

The complexity of real systems makes the control of their formulation a very tough issue, but the number of degrees of freedom and its variety also provide to the expert formulator many possibilities to tackle the most intricate problems. The experience indicates that the few months of training needed to gain an advanced know-how and a practical expertise in formulating microemulsions are a most profitable education that returns to the formulator a time-saving capacity worth thousand times the investment. 

The phenomenon of microemulsification is mainly governed by factors such as (1) nature and concentration of the oil, surfactant, co-surfactant and aqueous phase, (2) oil/surfactant and surfactant/co-surfactant ratio, (3) temperature, (4) pH of the environment and (5) physicochemical properties of the API such as hydrophilicity/lipophilicity, plimportant factors to be considered is acceptability of the oil, surfactant and co-surfactant for the desired route of administration. This factor is very important while developing micro emulsions for parenteral and ocular delivery as there is only limited number of excipients which are approved for the parenteral and ocular route. In Chapter 3 of this book a more general overview of formulating microemulsions is given and formulation considerations with respect to the components of microemulsions used in pharmaceutical applications are discussed below. 

Basically, two types of protocols have been proposed for EOR [110-114, 138]. One of them uses a high volume of diluted surfactant solution, while the other uses a small volume of highly concentrated surfactant solution. Early results obtained by EOR researchers both in the laboratory and pilot showed that by injecting a properly formulated microemulsion and letting it dilute in the reservoir fluids, a very low tension is maintained even at a surfactant concentration lower than 1 wt.% [113,114]. This indicates that the low surfactant concentration protocol is technologically feasible to recover a large proportion of extra oil [112-114,138,140],... 

A lot of studies on formulating microemulsions for EOR were carried out in the decade 1973-1983 [109-112, 115, 117-131] where crude oil prices were high. About three billon... 

Wu, B., Shiau, B.-J., Sabatini, D.A. andHarwell, J.H. (2000) Formulating microemulsion systems for a weathered Jet fuel waste using surfactant/cosurfactant mixtures. Separation Sci. Technol., 35(12), 1917-1937. 

A second pharmacodynamic study showed a significant reduction in pain perception of prods with von Frey hairs during the apphcation of two lidocaine formulations (microemulsion and 5% xylocaine), disconible from placebo treatment... 

It can be seen from Table 6 that anionic, cationic, and nonionic surfactants have all been exploited in formulating microemulsions for materials synthesis. Anionic and nonionic surfactants appear to be the most popular types of surfactants, with Aerosol OT (AOT) and the polyoxyethylated alkylphenyl ether surfactants (e.g., NP-5) leading. Part of the attraction of AOT and the NP surfactants is related to the fact that they permit microemulsion formulation without the need for cosurfactants. Also, a large body of information is already available on the phase behavior and structure of AOT microemulsions [121], and this makes it convenient to work with this anionic surfactant. A unique advantage of the nonionic surfactants is the fact that their use does not involve the introduction of (potentially undesirable) counterions. The ability to alter the size of the hydrophilic (oxyethylene) groups and/or the hydrophobic (alkyl) groups provides additional flexibility in surfactant selection. 

HLADH has also been used for the preparative reduction of water-insoluble substrates such as cinnamaldehyde [113], cyclohexanone [112], and the steroid eticholane-3/f-ol-17-one [112] with simultaneous oxidation of low molecular weight alcohols. With sodium dodecyl sulfate (SDS) or AOT as surfactant, enzyme activity was very dependent on the amount of water added. Relatively high water content gave the highest reaction rate and also the best enzyme stability. A properly formulated microemulsion gave a higher reaction rate than an aqueous buffer [112]. 

The same liquid phase (L3) as is formed by wheat lipids can be obtained in aqueous systems of rye lipids [2] and of oat lipids [3]. Oats are probably the food material richest in polar lipids, and it is therefore realistic to expect industrial production of oat lipids in the future in order to formulate microemulsions for foods. We have found (unpublished observations) that even large protein molecules can be encapsulated into this kind of L3 phase without being denatured. The incorporation of enzymes in L2 and L3 phases, for example, can provide protection against proteolytic degradation. 

Kunz W, Zemb T, Harrar A (2012) Using ionic liquids to formulate microemulsions current state of affairs. Curr Opin Coll Interf Sci 17 205-211... 

To overcome the limitations of the HLB method to formulate microemulsions, a different approach called hydrophilic-lipophilic difference (HLD) was developed by Salager et al. (1983, 2000). The HLD approach captnres the impact of various factors on microemnlsion type. The HLD value for nonionic and ionic snrfactants can be calculated as follows (Acosta and Bhakta 2009) Nonionic surfactants ... 

Frequently, phase separation effected upon incorporation of additives or cosolvents is a major concern when developing novel fuel formulations. Microemulsion-based mixtures can overcome this problem, and has been the focus of more recent works. In that respect, Friberg and Force, in 1976, patented a diesel-based microemulsion formulation that could be used as fuel, with reduced NO emissious when compared to pure diesel [52]. Subsequent works have focused on phase behavior, stability, and performance of different mixtures, most of which involving surfactant-based mixtures [26,39], but it is worth considering the recent advances in the use of microemulsified systems incorporating other fluids like vegetable oils and alcohols. 

Rather than fix the water/salt ratio as a brine pseudocomponent, another useful possibility is to fix the alcohol/ionic surfactant ratio as the pseudo-component (fix 8) and vary the salt concentration. An increase of the lyotropic salt concentration in ionic surfacant plus alcohol cosurfactant systems has the same effect as increasing temperature or salt in nonionic surfactant mixtures - a lipophilic shift is observed, and the phase behaviour progresses from 2 to 3 to 2 (15). If salt is placed in the position occupied previously by the cosurfactant in Figure 4.8, and the fixed ratio of alcohol/ionic surfactant placed as a combined pseudocomponent (fixed 5) at the surfactant position, at equal amounts of oil and water (a = 0.5) a plot of salt concentration (e) versus overall cosurfactant/surfactant concentration (y) also yields a fish -shaped phase diagram (45). Therefore, in either the case of fixed salt concentration (fixed ) or the case of fixed alcohol/ionic surfactant ratio (fixed 8), the optimally formulated microemulsions for the chosen fixed ratio of 8 or s, are found at X, where the tail and body of the fish meet (see Figure 4.8). Consequently, the phase behaviour of simple monodisperse ethoxylated alcohol surfactants in oil and water qualitatively mimics that of much more complicated mixtures containing ionic surfactants, cosurfactants and salt. Alcohol... 

For example, using the same system highlighted above (Ci2E5/octane/water), the interfacial tension between oil and water as a function of temperature exhibits a sharp inverted cusp, with the minimum and ultra-l( interfacial tension (5 x 10 " mN m ) found at T (Figure 4.15(c)). Optimally formulated microemulsions with high solubilization of oil and water exhibit the lowest interfacial tensions. Note, however, that the interfacial tension curves and the characteristic sizes exhibit exactly the opposite dependence as the mean curvature changes (see Figure 4.15). 

Figure 24 Effect of different alcohols on the solubilization in an optimum formulation microemulsion. Conditions 0.020 M ethoxylated alkylphenol, 0.0325 M n-alcohol, isooctane, T = 25 C, WOR = 1. [Reprinted with permission from Ref. 84. Copyright 1993 American Chemical Society.]...

Ionic surfactants have been used to formulate microemulsions. However, their toxic nature at concentrations normally encountered in microemulsions limits their application in foods (Alander and Wamheim, 1989 Flanagan et al, 2006). 

Uses Emulsifier for formulating microemulsions for cleaning of vehicles and for engineering applies. 

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