Water-in-oil nanoemulsions

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. 

Shakeel, F. Ramadan, W. Transdermal delivery of anticancer drug caffeine from water-in-oil nanoemulsions. Colloids Surf. B Biointerfaces 2010, 75 (1), 356-362. 

Zhi J, Wang Y, Luo G. Adsorption of diuretic furosemide onto chitosan nanopatticles prepared with a water-in-oil nanoemulsion system. React Funct Polym. 2005 65(3) 249-57. 

Water-in-oil (W/O) nanoemulsion Water droplets distributed in the oil phase. 

Alginate-coated chitosan core nanoparticles loaded with rabeprazole, an antiulcer agent which is chemically instable in the stomach, were developed using water-in-oil (W/O) nanoemulsion technique. The drug permeation from the prepared NP was significantly higher and controlled RP release compared to the pure drug [106],... 

To achieve the above criteria complex multipheise systems are formulated (i) Oil-in-Water (0/W) emulsions (ii) Water-in-Oil (W/0) emulsions (iii) solid/liquid dispersions (suspensions) (iv) emulsions-suspension mixtures (suspoemulsions) (v) nanoemulsions (vi) nanosuspensions (vii) multiple emulsions. All these disperse systems require fundamental understanding of the interfacial phenomena involved, such as the adsorption and conformation of the various surfactants and polymers used for their preparation. This will determine the physical stability/instability of these systems, their application and shelf-life. 

Porras, M., Solans, C., Gonzalez, C., and Gutierrez, J.M., Properties of water-in-oil (W/O) nanoemulsions prepared by a low-energy emulsification method. Colloids Surf. A Physicochem. Eng. Aspects, 2008, 324,181-188. 

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. 

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]. 

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. 

Many lipophilic drugs are formulated as oil-in-water (0/W) nanoemulsions. The drug may be an oil with low viscosity which can be directly emulsified in water using a surfactant such as lethicin or castor oil ethoxylate. For viscous drug oils, the latter... 

A study of the phase behavior of water/oil/surfactant systems demonstrated that emulsification can be achieved by three different low energy emulsification methods (A and B as schematically shown in Fig. 2.8). Method A stepwise addition of oil to a water surfactant mixture. Method B stepwise addition of water to a solution of the surfactant in oil. Method C mixing all the components in the final composition, pre-equilibrating the samples prior to emulsification. In these studies, the system water/Brij 30 (polyoxyethlene lauryl ether with an average of 4 moles of ethylene oxide)/decane Wcis chosen as a model to obtain 0/W emulsions. The results showed that nanoemulsions with droplet sizes of the order of 50 nm were formed only when water was added to mixtures of surfactant and oil (method B) whereby inversion from W/0 emulsion to 0/W nanoemulsion occurred. 

The rate of Ostwald ripening is 1.1 x 10 and 2.4 x 10 m /s at 1.6 and 2.4% HMI, respectively. These rates are 3 orders of magnitude lower than those obtained using a nonionic surfactant. Addition of 5% glycerol was found to decrease the rate of Ostwald ripening in some nanoemulsions, which may be due to the lower oil solubility in the water-glycerol mixture. 

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. 

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. 

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,... 

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). ... 

In pharmaceutical preparations, soybean oil emulsions are primarily used as a fat source in total parenteral nutrition (TPN) regimens. Although other oils, such as peanut oil, have been used for this purpose, soybean oil is now preferred because it is associated with fewer adverse reactions. Emulsions containing soybean oil have also been used as vehicles for the oral and intravenous administration of drugs drug substances that have been incorporated into such emulsions include amphotericin, " diazepam, retinoids, vitamins, poorly water-soluble steroids, fluorocarbons, and insulin. In addition, soybean oil has been used in the formulation of many drug delivery systems such as liposomes, microspheres, dry emulsions, self-emulsifying systems, and nanoemulsions and nanocapsules. ... 

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. 

In these studies, the system water/Brij 30 (polyoxyethylene lauryl ether with an average of 4mol ethylene oxide/decane) was chosen as a model to obtain O/W emulsions. The results showed that nanoemulsions with droplet sizes on the order of 50 nm were formed only when water was added to mixtures of surfactant and oil (method B), whereby an inversion from a W/O emulsion to an O/W nanoemulsion occurred. 

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