Nanoemulsions

The term nanoemulsion naturally creates confusion with the term microemulsion. One may think that nanoemulsions have droplets smaller than microemulsions, since the prefix nano indicates a quantity three orders of magnitude smaller than a quantity indicated by the prefix micro. As mentioned earlier in the chapter, the term microemulsion is not well chosen, but it is too well established to change it. 

Microemulsions are thermodynamically stable phases, which can be represented by clear areas in equilibrium phase diagrams. Nanoemulsions are really small emulsions, with the main characteristics of emulsions they are not thermodynamically stable and the way they are prepared has a great impact on their physical stability. The only difference with common emulsions is their very small droplet size, which ranges from 10 to 500 nm. Accordingly, nanoemulsions may look bluish, due to light diffusion (brown/yellow by transmission), just like microemulsions close to a critical point. 

In contrast to thermodynamically stable microemulsions, nanoemulsions can be highly efficient in releasing oily materials. Indeed, they are highly metastable the droplet size is small, but the interfacial tension is not so small. This results in the Laplace pressure inside the droplets being very high. Metastability is due to the activation energy required for two droplets to merge. 

These are emulsion systems with a size range of 20 to 200 nm. Like emulsions, they are only kineticaUy stable but, due to the very small size, they have much longer physical stability  

These are transparent or translucent systems covering the size range from 5 to 50nm. Unlike emulsions and nanoemulsions (which are only kinetically stable), microemulsions are thermodynamically stable as the free energy of their formation is either zero or negative. Microemulsions are better considered as swollen micelles normal micelles can be swollen by some oil in the core of the micelle to form O/W microemulsions. Reverse micelles can be swollen by water in the core to form W/O microemulsions. 

The driving force for microemulsion formation is the ultra-low interfacial tension which is normally obtained by using two surfactants one which is predominantly 

An analogous equation has been developed (Anton, 1997) for cationic surfactant-based microemulsions. 

For POE nonionic surfactant-based microemulsions, equation 8.11 has been suggested (Bourrel, 1980)  

EON is the average number of oxyethylene groups in the surfactant hydrophilic group, 

The volume of the oil phase (in mL) solubilized per gram of surfactant used at the conditions where equations 8.10 or 8.11 are equal to zero ( optimum salinity ) is called the solubilization parameter at optimum formulation and symbolized by SP. The interfacial tension under these conditions, y, is inversely proportional to the SP, and y = K/(SP )2 (Chun, 1979). Consequently, to obtain the lowest interfacial tension (Chapter 5, Section IIIA), the value of SP should be maximized. 

Lipophilic linkers (Salager, 1998) and hydrophilic linkers (Uchiyama, 2000 Acosta, 2002) are used to increase the value of SP and decrease y. Lipophilic linkers are long-chained alcohols (above C8) and their low oxyethylenation products that increase the surfactant-oil interaction. The most effective ones have hydrophobic chain lengths that are an average of the hydrophobic chain length of the surfactant and the chain length of the alkane oil. Hydrophilic linkers increase the surfactant-water interaction. Examples are mono- and dimethylnaphthalene sulfonates and sodium octanoate 

---

Formation of Nanoemulsions by Low-Energy Methods and Their Use as Templates for the Preparation of Polymeric Nanoparticles... 

The formation of ethylcellulose nanoemulsions by a low-energy method for nanoparticle preparation was reported recently. The nanoemulsions were obtained in a water-polyoxyethylene 4 sorbitan monolaurate-ethylcellulose solution system by the PIC method at 25 °C [54]. The solvent chosen for the preparation of the ethylcellulose solution was ethyl acetate, which is classed as a solvent with low toxic potential (Class 3) by ICH Guidelines [78]. Oil/water (O/W) nanoemulsions were formed at oil/ surfactant (O/S) ratios between 30 70 and 70 30 and water contents above 40 wt% (Figure 6.1). Compared with other nanoemulsions prepared by the same method, the O/S ratios at which they are formed are high, that is, the amount of surfactant needed for nanoemulsion preparation is rather low [14]. For further studies, compositions with volatile organic compound (VOC) contents below 7 wt% and surfactant concentrations between 3 and 5 wt% were chosen, that is, nanoemulsions with a constant water content of 90% and O/S ratios from 50 50 to 70 30. 

Figure 6.1 O/W nanoemulsion region in the water/polyoxyethylene 4 sorbitan monolaurate/ [10%ethylcellulose (EC10) in ethyl acetate] system at 25 °C. Reproduced with permission from [54].

Phase inversion along the dilution path (by addition of water to the oil/surfactant mixture) followed for nanoemulsion preparation was confirmed by conductivity measurements, and was found to be essential for obtaining finely dispersed systems, as transparent dispersions were not obtained if the order of addition of the components was changed following an experimental path with no phase inversion (Figure 6.2). 

The droplet sizes of the nanoemulsions characterized by dynamic light scattering at O/S ratios between 50 0 and 70 30 and a constant water content of 90 wt% were between 200 and 220 nm, displaying a slight increase with increasing O/S ratio. Figure 6.3 shows atypical cryo-transmission electron microscope (TEM) image of an... 

Figure 6.3 Cryo-TEM image of the nanoemulsions of the water/polyoxyethylene 4 sorbitan monolaurate/[10% EClOin ethyl acetate] system with an O/S ratio of70 30and a water content of 90 wt%.

The nanoemulsion mean droplet sizes were much smaller than those obtained in other systems using polar oil mixtures (above 500 nm) [18]. The findings verify that the low-energy emulsification methods are valid not only for aliphatic [9,10,13, 75, 76, 79-81] and semipolar oils [82-84], as reported in most studies devoted to low-energy emulsification, but also for polar solvent-preformed polymer mixtures. These nanoemulsions show good kinetic stability at 25 °C over a period of at least 24 h,... 

Figure 6.4 TEM image of the dispersion of nanoparticles obtained after evaporation of the solvent of a nanoemulsion with an O/S of 70 30 and a water content of 90wt% and negative staining with a phosphotungstic acid solution. Reproduced with permission from [54].

The particle size was below 50 nm (as determined by TEM image analysis), considerably smaller than that of the starting nanoemulsion, and showed a slight mean particle size increase and a broader size distribution with increasing O/S ratio, supporting the template effect of the nanoemulsion. The authors showed that these nanoparticles are interesting not only from a basic viewpoint but also for applications where safety and environmental concerns are important issues. 

Morales, D., Gutierrez, J.M., Garcia-Celma, M.J. and Solans, C. (2003) A study of the relation between bicontinuous microemulsions and oil/water nanoemulsion formation. Langmuir, 19, 7196-7200. 

Hwang, T.-L., Fang, C.-L., Chen, C.-H. and Fang, J.-Y. (2009) Permeation enhancer-containing water-in-oil nanoemulsions as carriers for intravesical cisplatin delivery. Pharmacological Research, 26 (10), 2314-2323. 

Klang, V., Matsko, N., Zimmermann, A.M., Vojnikovic, E. and Valenta, C. (2010) Enhancement of stability and skin permeation by sucrose stearate and cydodextrins in progesterone nanoemulsions. International Journal of Pharmaceutics, 393, 152—160. 

Ganta, S. and Amiji, M. (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Molecular Pharmacology, 6 (3), 928-939. Sonneville-Aubrun, O., Simonnet, J.-T. and L Alloret, F. (2004) Nanoemulsions a new vehicle for skincare products. Advances in Colloid and Interface Science, 108-109, 145-149. 

Maruno, M. and da Rocha-Filhoa, P.A. (2010) O/W nanoemulsion after 15 years of preparation a suitable vehicle for pharmaceutical and cosmetic applications. Journal of Dispersion Science and Technology, 31, 17-22. 

Caldero, G., Pi Subirana, R., Llosas Bigorra, J. and Torres Fernandez, M. (2001) Use of alkyl(ether) phosphates (I). European Patent EP 1264633. Sonneville-Aubrun, O. and Simonnet, J.-Th. (2001) Nanoemulsion based on anionic polymers, and uses thereof especially in the cosmetic, dermatological, pharmaceutical and/or ophthalmic fields. European Patent EP 1160005. 

Wang L., Li, X., Zhang, G., Dong, J. and Eastoe, J. (2007) Oil-in-water nanoemulsions for pesticide formulations. Journal of Colloid and Interface Science, 314, 230-235. 

Qian, C. and McClements, D.J. (2011) Formation of nanoemulsions stabilized by model food-grade emulsifiers using high-pressure homogenization factors affecting particle size. Food Hydrocolloids, 25 (5), 1000-1008. 

Lee, S.J. and McClements, D.J. (2010) Fabrication of protein-stabilized nanoemulsions using a combined homogenization and amphiphilic solvent dissolution/evaporation approach. Food Hydrocolloids, 24, 560-569. 

Anton, N., Benoit, J.P. and Saulnier, P. (2008) Design and production of nanopartides formulated from nanoemulsion templates - a review. Journal of Controlled Release, 128, 185—199. 

Wang, L., Tahor, R., Eastoe, J., Li, X., Heenan, R.K. and Dong, J. (2009) Formation and stability of nanoemulsions with mixed ionic—nonionic surfactants. Physical Chemistry Chemical Physics, 11, 9772-9778. 

Yang, H.J., Cho, W.G. and Park, S.N. (2009) Stability of oil-in-water nanoemulsions prepared using the phase inversion composition method. Journal of Industrial and Engineering Chemistry,... 

Antimicrobial acrylic fibers, 11 215-219 Antimicrobial agents, 12 31. See also Antimicrobial compounds in continuous-filament yarns, 19 758 as preservatives, 12 57-59 silylating agents and, 22 700 as soap bar additives, 22 746 sulfonamides as, 23 494 Antimicrobial compounds, microbiological methods for determining, 20 132 Antimicrobial nanoemulsion technology, 3 630-631... 

Disinfection, 8 605-672. See also Disinfection processes antimicrobial nanoemulsion technology, 8 630-631 bromine, 8 621-626 bromine chloride, 8 626-628 chlorination, 8 610-615 chlorine dioxide, 8 617-619 dechlorination with sulfur dioxide, 8 615-617... 

The drug dissolved or dispersed in the melted lipid is poured into an aqueous emulsifier phase of the same temperature. By means of a rotor-stator homogenizer (e.g., an Ultra-Turrax), an o/w preemulsion is prepared and is then homogenized at high pressure and at a temperature at least 10°C above the melting point of the lipid. In most cases, nanoemulsion arises after only three to live homogenization cycles at 500 bar. Nanoparticles are formed by cooling the nanoemulsion to room temperature. 

When a NAPL reaches the subsurface, it may by subject to mechanical forces that lead to the formation of a mixed NAPL-water micro-/nanoemulsion characterized by the presence of micro- and nanodroplets of organic compounds. These micro- and nanoemulsions are transparent or translucent systems, kinetically (nano-) or thermodynamically (micro-) stable, and display an apparent increase in aqueous solubility as compared to the intrinsic solubility of the NAPL itself (Tadros 2004). The very small droplet size (50-200 nm in the case of a nanoemulsion) causes a large reduction in the force of gravity, enabling the system to remain dispersed and... 

TEMPO has been structurally modified to bring about new selectivities. Highly efficient anionic water-soluble TEME<), oil-in-water nanoemulsion containing TEME for oxidation of alcohols and a waste-free system were developed. Especially, the sterically less crowded azabicyclo-Af-oxyls oxidized /-menthol to Z-menthone with much higher efficiencies than TEME O (equation 23). ... 

---