Nano-emulsions applications

The majority of active ingredients to be solubilized are amphiphilic and relatively big molecules, so their solubility must be studied for developing the corresponding nano-emulsion applications. 

Gutierrez, J.M., Gonzalez, C., Maestro, A., Sole, I., Pey, C.M. and Nolla., J. (2008) Nano-emulsions new applications and optimization of their preparation. Current Opinion in Colloid and Interface Science, 13, 245-251. 

Sadurni, N., Solans, C., Azemara, N, and Garcia-Celma, M. J. (2005), Studies on the formation of O/W nano-emulsions, by low-energy emulsification methods, suitable for pharmaceutical applications, Eur. J. Pharm. Sci., 26,438-445. 

Much of the work in this area has been done in emulsions having a droplet size of more than 1 pm, and the application of submicron (nano) emulsions in encapsulation of oils and flavors is relatively new in the literature. Some works have been carried out to determine the influence of submicron emulsions produced by different emulsification methods on encapsulation efficiency and to investigate the encapsulated powder properties after SD for different emulsion droplet sizes and surfactants. The process has been referred to as nanoparticle encapsulation since a core material in nanosize range is encapsulated into a matrix of micron-sized powder particles (Jafari et al., 2008). This area of research is developing. Some patents were filed in the past describing microemulsion formulations applied to flavor protection (Chung et al., 1994 Chmiel et al., 1997) and applications in flavored carbonated beverages (Wolf and Havekotte, 1989). However, there is no clear evidence on how submicron or nanoemulsions can improve the encapsulation efficiency and stability of food flavors and oils into spray-dried powders. 

Nano-emulsions are attractive for application in personal care and cosmetics as well as in health care due to the following advantages ... 

Two methods may be applied for the preparation of nano-emulsions (covering the droplet radius size range 50-200 nm). Use of high-pressure homogenisers (aided by appropriate choice of surfactants and cosurfactants) or application of the phase inversion temperature (PIT) concept. 

One of the main advantages of nano-emulsions is the high occlusive film that may be formed on application to the skin. The small size droplets can enter the rough surface of the skin and the droplets may form a close packed structure on the skin surface. This is particularly the case when the droplets have high viscosity or are solid-like . Another useful application of nano-emulsions is the ability to enhance penetration of actives (e.g. vitamins, antioxidants, etc.) into the skin. This is due to their much higher surface area when compared with coarser emulsions. 

In this chapter we will start with a section on the raw materials used to produce HMI, the possible production methods of this product and its safety. The second section will give a short description of the solution properties of long-chain inulin and HMI. This is followed by a section on the interfacial properties of HMI at the air/liquid, liquid/liquid and solid/liquid interfaces. Particular attention will be given in describing the effectiveness of HMI as a stabilizer for various disperse systems, e.g. emulsions, nanoemulsions and latexes. The application of HMI in the formulation of emulsions, latex dispersions and nano-emulsions will be described in subsequent sections. 

In this chapter, nano-emulsion formation by low-energy emulsification methods, with special emphasis on phase inversion methods and their relation to surfactant phase behavior will be discussed first. This will be followed by an analysis of nano-emulsion functional characteristics. The relation with their structure is discussed regarding the applications in which they are relevant. Prior to discussing nano-emulsion functional characteristics, the main nano-emulsion destabilization mechanism, Ostwald ripening, is described. 

The majority of publications on nano-emulsions emphasize their potential applications, comparing them with conventional emulsions (macroemulsions) and microemulsions. With respect to macroemulsions, the main advantage of nano-emulsions would be the smaller droplet size, whereas with respect to microanulsions the main advantage would be the lower amount of surfactant needed for their stabilization. The possibilities of developing applications are mainly limited by stability [2], which is of conrse related to the structure of nano-emulsions, and can be considered a functional characteristic. On the other hand, the potential applications of nano-emulsions depend on their functional characteristics. 

In this section, the functional characteristics of nano-emulsions and the relation with their structure are analyzed and discussed in relation to the applications in which these functional characteristics can be important. The section is divided according to the main functional characteristics determining the applications of nano-emulsions stability, droplet size, and solubilizing capacity. 

It may seem that due to the different mechanisms and factors influencing the stability of nanoemulsions it is not possible to know a priori which will be the behavior of a defined system. However, the growing knowledge about a great variety of systems and a wise use of this knowledge would allow the formulation of nano-emulsions with enough stability for the applications intended. 

From the earlier studies on nano-emulsion, their potential application for the preparation of nanoparticles with similar sizes as those of the nano-emulsion droplets has been claimed. In an early work about the preparation of nanoparticles from nano-emulsions (referred as miniemulsions), Ugelstadt [3] proposed a polymerization mechanism with nucleation in the miniemulsion droplet, as a different mechanism to that of macroemulsion polymerization, where nucleation takes place mainly in micelles. This mechanism can result in particles as one-to-one copy from nano-emulsion droplets, and this possibility is deeply discussed in a review by Asua [18] (Figure 21.12). 

Another type of application of nano-emulsions where the droplet size could be a key factor is their application as delivery systems, provided that delivery of active components would be more efficient than in conventional emulsions, or macroemulsions. It has been reported that droplet size may influence the delivery of active ingredients [71,15], however, in a recent work Izquierdo et al. [72] have shown that the delivery rate of an active ingredient (a local anesthesic) through the skin is not significantly affected by droplet size (Figure 21.13). It should be noted that contrary to most of... 

As a partial conclusion of this subsection, influence of droplet size of nano-emulsions on their functional applications would depend on the very specific characteristics of application and on the system used. Consequently, each system should be specifically studied. It may seem that extensive experimental study should be needed for each new application based on droplet size. However, the accumulated knowledge that can be extracted from experimental published work, especially in the recent years, should allow theoretical predictions about the influence of droplet size and savings in experimental work. 

The capacity of solubilizing compounds in the droplets of a nano-emulsion gives the possibility of developing applications, implying the transport of these compounds through a continuous phase in which they are insoluble. Pharmaceutical and cosmetic applications for which nonpolar compounds are solubilized in oil droplets dispersed in aqueous media would be typical, and other possible applications in food or agrochemical fields have also been described [1,2],... 

If only the solubility in individnal components is taken into acconnt, the possible application of 90% or 95% nano-emulsions wonld be discarded because it would seem that therapeutic concentrations could not be reached. However, the experimental results show that even in diluted nanoemulsion such as those with 95% water, a concentration of 2.1% active ingredient, within the therapentic range, can be reached. In a different system, Shakeel et al. [73] showed that the solubilizing capacity is a very critical factor because the active ingredient, aceclofenac, is a very insoluble compound. In this work, stndies of solubility in a wide variety of oils and surfactants are described, and the best system was a mixture of oils. Oils and surfactants are selected with the solubility as main criteria. As a main conclusion of this subsection, and from the described examples, the convenience of specific study of the solubility behavior for each system or possible application is pointed out. The experimental work to be made seems enormous given the variety of oils, surfactants, and experimental conditions. However, one approach would be to first focus on systems for which previous information can be obtained, and if selection is made taking into account wise criteria the amonnt of work could be considerably reduced. 

Nano-emulsions are defined as a class of emulsions with uniform and extremely small droplet size (typically in the range 20-500 nm). The formation of kinetically stable liquid/hquid dispersions of such small sizes is of great interest from fundamental and applied viewpoints. In this review, nanoemulsion formation, with special emphasis on low-energy emulsification methods, is first discussed. This is followed by a description of nano-emulsion properties, focusing on their kinetic stability. Finally, relevant industrial applications of nano-emulsions in the preparation of latex particles, in personal-care formulations, and as drug dehvery systems are reported. 

Nano-emulsions are a class of emulsions with uniform and extremely small droplet size (typically in the range 20-500 nm). Because of their characteristic size, some nano-emulsions appear ttansparent or translucent to the naked eye (resembling microemulsions) and possess stability against sedimentation or creaming. Nano-emulsions of the oil-in-water (OAV) type have been investigated and used in practieal applications for a long time [1-5]. However, they have experienced growing interest and very active development in recent years, as reflected by publications [6-16] and patents [17-27] on this subject. 

Although nano-emulsions are thermodynamically imstable systems, they may possess high kinetic stability. This property together with their transparent or translucent visual aspect and a viscosity similar to that of water makes them of special interest for practical applications. Nano-emulsions are used in the pharmaceutical field as drug delivery systems [8,17, 18,25,28-33], in cosmetics as personal-care formulations [2,4,6,7,10,19-21,23,24,27], in agrochemical applications for pesticide delivery [3,34,35], in the chemical industry for the preparation of latex particles [9,22,26,36-38], etc. In addition, the formation of kinetically stable liquid/liquid dispersions of such small sizes is of great interest from a fimdamental viewpoint. 

In this chapter, different methods for nano-emulsion formation, with special emphasis on low-energy emulsification methods, are discussed in Section 11. This is followed by a description of nano-emulsion stability (Section 111). Finally, the most relevant applications of nano-emulsions are reviewed... 

Nano-emulsions have found increasing use in many different applications. The advantages of nano-emulsions over conventional emulsions (or macroemulsions) are a consequence of their characteristic properties, namely small droplet size, high kinetic stability, and optical transparency. In addition, nano-emulsions offer the possibility of using microemulsion-like dispersions without the need for high surfactant concentrations. In the following, the most relevant applications of nano-emulsions in the chemical, pharmaceutical, and cosmetic fields are summarized. 

The transparent visual aspect of nano-emulsions with droplet sizes below 200 nm makes them especially attractive for application in cosmetics. Apart from the appearance, similar to that of microemulsions, other advantages of nano-emulsions for cosmetic applications are their kinetic stability, a droplet size that can be controlled, and the possibility to achieve improved active delivery. For all these reasons, nano-emulsions have attracted increasing interest in the cosmetic field, as reflected by the papers [8,10,106] and numerous patents [19-21,23,24,27,107-111] that have appeared in the last few years. Oil-in-water nano-emulsions with a droplet size lower than 100 nm have been described in patents as hair- and skin-care [19,21,23,24,107-109], makeup [110], and sunscreen [20,111] formulations. 

The use of ttaditional disperse systems, e.g., macroemulsions, in the pharmaceutical industry has been limited due to manufacturing complexity and stability problems [117]. The characteristic properties of nano-emulsions (kinetic stability, small and controlled droplet size, etc.) make them interesting systems for pharmaceutical applications. Indeed, nano-emulsions are used as drug delivery systems for administration through various systemic routes. There are numerous publications on nano-emulsions as drug delivery systems for parenteral [17,18,28,29,118-124], oral [25,125-129], and topical administration, which includes the administration of formulations to the external surfaces of the body skin [32,130,131] and to the body cavities nasal [30,132] as weU as ocular administration [31,133-136]. Moreover, many patents concerning pharmaceutical applications of nano-emulsions have been registered [17,18,25,137-145]. An application of nano-emulsions in this field has been in the development of vaccines [33,146-147]. 

Another application of nano-emulsions in the pharmaceutical field is in ocular administration (a topical administration). Nano-emulsions are used as ocular delivery systems to sustain the pharmacological effect of drugs in comparison with their respective aqueous solutions [133]. 

In this chapter, the characteristic properties of nano-emulsions and relevant applications have been described. A great deal of research effort in recent years has been focused toward the conditions required for nano-emulsion formation. Low interfacial tension values and the presence of lamellar liquid crystalline phases are among the factors that have been shown to be important for their formation. However, it has also been shown that the kinetics of the emulsification process plays a key role. Comprehensive knowledge of the fundamental aspects related to nano-emulsion formation and stability will allow improvement of established applications, such as those described in this chapter, and development of new ones. 

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