W/O nanoemulsion

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].

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. 

Unlike microemulsions (which require a high surfactant concentration, usually in the region of 20% and higher for a 20% microemulsion), nanoemulsions can be prepared using reasonable surfactant concentrations. For a 20% O/W nanoemulsion, a surfactant concentration in the region of 5% may be sufficient... 

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. 

O/W nanoemulsions with droplet radii in the range 26-66 nm could be obtained at surfactant concentrations between 4% and 8%. The nanoemulsion droplet size and polydispersity index was shown to decrease with increases in surfactant concentration this effect was considered due to the to the increase in surfactant interfadal area and the decrease in interfacial tension, y. 

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. 

Phase inversion methods are based on spontaneous O/W nanoemulsion formation induced by controlling the interfacial behavior, from predominantly lipophilic to predominantly hydrophilic, of the surfactants at the O/W interface, in response to changes in system compositions or environmental conditions. ... 

V. Unlike microemulsions, which need a high amount of surfactant to be more than 20%, nanoemulsions can be formulated by very minute amounts of surfactants. Formulation of 20% o/w nanoemulsion required less than 10% of surfactant. 

FIGURE 21.1 Schematic representation of a typical phase diagram of a ternary water/nonionic surfactant/ oil system as a function of temperature and surfactant content at constant O/W weight ratio (/ ). O/W nanoemulsion formation paths by the PIT method are indicated by arrows. The process starts from a bicontinuous microemulsion (D), path (a) an inverse microemulsion (0 ), path (b, point 2 ) a lamellar liquid crystal (L ), path (b, point 2), and a three-phases region (W + D + O), path (c). (1) indicates compositions below the HLB temperature where all components are mixed and where O/W nano-emulsions are formed), (2) indicates compositions at the HLB temperature, and (3) indicates compositions above the HLB temperature. 

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. 

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. 

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. 

The small size of the droplets allows nanoemulsion to be deposited uniformly on substrates. Wetting, spreading and penetration may be also enhanced as a result of the low surface tension of the whole system and the low interfacial tension of the O/W droplets. 

Near the HLB temperature, the interfacial tension reaches a minimum, as illustrated in Figure 14.4. Thus, by preparing the emulsion at a temperature 2-4 °C below the PIT (near the minimum in y), followed by rapid cooling of the system, nanoemulsions may be produced. The minimum in y can be explained in terms of the change in curvature H of the interfacial region, as the system changes from O/W to W/O. For an O/W system and normal micelles, the monolayer curves towards the oil such that H has a positive value. However, for a W/O emulsion and inverse micelles the monolayer will curve towards the water and H will be assigned... 

Figure 14.13 r versus time at 25 °C for nanoemulsions (O/W ratio 20/80) with hydrocarbons of various alkyl chain lengths. System water-C jEO -hydrocarbon (4wt% surfactant). 

Figure 14.18 r versus time for nanoemulsion systems prepared using the PIT and Microfluidizer. 20/80 O/W ratio and 4wt% surfactant. 

Nowadays the challenging job for pharmaceutical scientists is to increase the oral bioavailability of insulin for diabetic patients. Li et al. [42] developed an alginate/ chitosancoated nanoemulsion (w/o/w) containing insulin as the model protein. The coated nanoanulsion particle size was 488 nm, the polydispersion index was 0.396, and the entrapment efficiency of insulin was 47.3%. The surface morphology of the coated and uncoated nanoemulsion was done by TEM. The in vitro result stated that the nanoemulsion was stable at gastric pH. Hypoglycemic effect and relative bioavailability were performed in a rat model. 

The o/w lipid nanoemulsions have many appealing properties as drug carriers of poorly aqueous soluble or lipophilic active molecules that exhibit complex formulation problems when designed to be incorporated in fluid aqueous vehicles for injectable and ocular application. They are biocompatible, biodegradable, physically stable, and relatively easy to produce on a large scale using proven technology. They can be formulated in a variety of formulations such as liquids, sprays. 

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