Nanoemulsions separation

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 particle sizing by field flow fractionation (FFF) is based on the different effect of a perpendicular applied field on particles in a laminar flow [63-66], The separation principle corresponds to the nature of the perpendicular field and may, for example, be based on different mass (sedimentation FFF), size (cross-flow FFF), or charge (electric-field FFF). Cross-flow FFF has been applied recently to investigate nanoemulsions, SLN, and nanostructured lipid carriers (NLC, particles composed of liquid and solid lipids) [58], Although all samples had comparable particle sizes in PCS, their retention in the FFF was very different. Compared to the spherical droplets of the nanoemulsion, SLN and NLC were pushed more efficiently to the bottom of the channel because of their anisotropic shape. Their very different shapes have been confirmed by electron microscopy. 

Although, the oil phase and the emulsifiers are the most important excipients in the design process of a specific nanoemulsion formulation, additives are further needed to adjust to physiological pH and tonicity, to protect nanoemulsions from oxidation and phase separation or drug degradation and sometimes from microbial contamination (preservatives) if nanoemulsion is intended for ocular administration. All ingredients used should be pharmaceutical grade materials. 

Thermodynamically, the change in free energy to formulate either a microemulsion or a nanoemulsion from two separate phases (i.e., AGf niation) can be expressed as follows (McClements 2012) ... 

Kinetically, the rate of separation of nanoemulsion into two separate phases can be described by the Arrhenius equation (Missen et al. 1999) ... 

Subsequently, Han et al. [34] reported IL-in-IL nanoemulsions for the first time. Assisted with a certain amount of surfactant AOT, the hydrophilic IL PAF and the hydrophobic IL 3-methyl-l-octylimidazolium hexafluorophosphate ([omimjPF ) formed [omimjPF -in-PAF microemulsions when the volume ratio of [omimjPF was relatively low. With the increase in volume ratio of [omimjPF, unstable [omim] PFj-in-PAF nanoemulsions were formed, which were transparent before phase separation. The conductivity of [omimjPF -in-PAF nanoemulsions was much lower than that of [omim]PFj-in-PAF microemulsions. Small-angle X-ray scattering (SAXS) experiment demonstrated that the microdroplets of the nanoemulsion were spherical and the gyration radii of the microdroplets decreased from 19.3 to 15.7 nm when the volume ratio of [omimjPF was reduced from 0.35 to 0.25. Utilizing this IL-in-IL nanoemulsion as the reaction medium, stable and crystallined metal-organic framework (MOF) nanorods were successfully synthesized, indicating potential applications of IL-in-IL nanoemulsions as well as microemulsions in other fields. 

The schematic representation of the variation of G ix, Gei and Ga with h given in Eigure 6.10 shows that there is only one minimum (Gmm), whose depth depends on R,S and A. When ho < 23, strong repulsion occurs and it increases very sharply with further decrease in ho- At a given particle size and Hamaker constant, the larger the adsorbed layer thickness, the smaller the depth of the minimum. If Gmin is made sufficiently small (large 3 and small R), one may approach thermodynamic stability. This explains the case with nanoemulsions, which will be discussed in a separate chapter. 

The inherently high colloid stability of nanoemulsions when using polymeric surfactants is due to their steric stabilization. The mechanism of steric stabilization was discussed above. As shown in Fig. 1.3 (a), the energy-distance curve shows a shallow attractive minimum at separation distance comparable to twice the adsorbed layer thickness 28. This minimum decreases in magnitude as the ratio between adsorbed layer thickness to droplet size increases. With nanoemulsions the ratio of adsorbed layer thickness to droplet radius (8/R) is relatively large (0.1 0.2) when compared with macroemulsions. This is schematically illustrated in Fig. 1.28 which shows the reduction in with increasing 8/R. 

However, some nano-emulsions can be rather stable against coalescence [75,76], One mechanism could be stabilization by a thick multilamellar surfactant film adsorbed on the interface [14,77], The phase separation of nanoemulsions can result in three-phase systems containing liquid crystals [14-16], These liquid crystalline phases could form multilayer film structures if enough surfactant were available. 

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