Phase nanoemulsions

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). 

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,... 

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. 

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]. 

Patents have been granted for innovations involving the preparation and activities of broad-spectrum antimicrobial emulsions from 1977 (Sippos) to 2000 (Baker). All of these patents claim antibacterial activity, but all involve additives in the non-aqueous phase of the emulsion that are known to be antibacterial alone and before emulsification. Wide spectrum applications for these nanoemulsions have been claimed with positive results for bacteria, fungi, and viruses. The term nanoemulsion is used in US patents discussed below, but the generic term for the product of an emulsification (Gooch 2002, 1980) of a liquid within a liquid is an emulsion. United States patents 6,015,832 and 5,547,677 were examined and formulations in key claim statements were reproduced, and tested using standard methods for effectiveness. Additional patents listed in the reference section were reviewed as part of this study. 

In this technique, a hydrophobic polymer is dissolved in an organic solvent, such as chloroform, ethyl acetate, or methylene chloride and is emulsified in an aqueous phase containing a stabilizer (e.g., PVA). Just after formation of the nanoemulsion, the solvent diffuses to the external phase until saturation. The solvent molecules that reach the water-air interphase evaporate, which leads to continuous diffusion of the solvent molecules from the inner droplets of the emulsion to the external phase simultaneously, the precipitation of the polymer leads to the formation of nanospheres. The extraction of solvent from the nanodroplets to the external aqueous medium can be induced by adding an alcohol (e.g. isopropanol), thereby increasing the solubility of the organic solvent in the external phase. A purification step is required to assure the elimination of the surfactant in the preparation. This technique is most suitable for the encapsulation of lipophilic drugs, which can be dissolved in the polymer solution. 

Nanoemulsions 20-25 nm poorly soluble chemical compounds by increasing solubility Drugs in oil and/or liquid phases to improve absorption... 

With emulsions, nanoemulsions and microemulsions, the surfactant adsorbs at the oil/water (O/W) interface, with the hydrophilic head group immersed in the aqueous phase and leaving the hydrocarbon chain in the oil phase. Again, the mechanism of stabilisation of emulsions, nanoemulsions and microemulsions depends on the adsorption and orientation of the surfactant molecules at the Uquid/liquid (L/L) interface. Surfactants consist of a small number of units and are mostly reversibly adsorbed, which in turn allows some thermodynamic treatments to be applied. In this case, it is possible to describe adsorption in terms of various interaction parameters such as chain/surface, chain solvent and surface solvent. Moreover, the configuration of the surfactant molecule can be simply described in terms of these possible interactions. 

Nanoemulsions may be apphed as a substitute for hposomes and vesicles (which are much less stable). It is also possible in some cases to build lamellar hquid crystalhne phases around the nanoemulsion droplets. 

A lack of understanding of the interfacial chemistry involved in production of nanoemulsions. For example, few formulations chemists are aware of the concepts of phase inversion composition (PIC) and phase inversion temperature (PIT), and how these can be usefuUy apphed to produce small emulsion droplets. 

One of the main problems with nanoemulsions is Ostwald ripening which results from differences in solubility between the small and large droplets. The difference in the chemical potential of dispersed phase droplets between different-sized droplets as given by Lord Kelvin [17],... 

In contrast to the results obtained with hexadecane, the addition of squalane to the O/W nanoemulsion system based on isohexadecane showed a systematic decrease in Ostwald ripening rate as the squalene content was increased. The results are included in Figure 14.14, which shows plots of versus time for nanoemulsions containing varying amounts of squalane. The addition of squalane up to 20% based on the oil phase showed a systematic reduction in ripening rate (from 8.0 to 4.1 x 10 m s i). It should be noted that when squalane alone was used as the oil phase, the system was very unstable and showed creaming within 1 h. The results also showed that the surfactant used was unsuitable for the emulsification of squalane. 

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. 

There are essentially two ways to prepare nanoemulsions. These are the phase inversion temperature (PIT) process and the high-pressure homogenization (HPH) process. 

Nanoscale emulsions have gained technological interest because the transport efficiency of functional components in emulsion food systems is increased when droplets are in the nanoscale (Spernath and Aserin, 2006). In addition, these emulsions are transparent, and they have lower viscosity when compared to conventional emulsions, which make them suitable for use in beverages, for example. In recent years, considerable research effort was made to understand the physical properties, preparation, phase behavior, and stability of micro- and nanoemulsions. 

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