**1. Introduction**

An ideal drug delivery system fulfils the objective of maximizing therapeutic effect while minimizing toxicity. With the progress in time and advances in science and technology, dosage forms have evolved from simple mixtures and pills, to highly sophisticated systems, which are known as novel drug delivery systems. Nanoemulsions are novel drug deliv‐ ery systems consisting of emulsified oil and water systems with mean droplet diameters ranging from 50 to 1000 nm. Usually, the average droplet size is between 100 and 500 nm and can exist as oil-in-water (o/w) or water-in-oil (w/o) form, where the core of the particle is either oil or water, respectively. Nanoemulsions (Figs. 1 and 2) are made from pharma‐ ceutical surfactants that are generally regarded as safe (GRAS). The surfactant type and concentration in the aqueous phase are chosen to provide good stability against coales‐ cence. Several types of oils-natural semi-synthetic and synthetic are used in the formula‐ tion of nanoemulsions. The capacity of nanoemulsions to dissolve large quantities of low soluble drugs along with their mutual compatibility and ability to protect the drugs from hydrolysis and enzymatic degradation make them ideal drug delivery vectors [1]. The major advantages of nanoemulsions as drug delivery carriers include increased drug loading, enhanced drug solubility and bioavailability, reduced patient variability, controlled drug release, and protection from enzymatic degradation [2].

A lot of techniques are available for enhancing absorption of poorly water-soluble drugs, like use of lipid-based systems. Thus enhancement of aqueous solubility in such case is a valuable goal to successfully formulate them into bioavailable dosage forms. A range of novel strategies are currently being developed for efficient delivery of poorly water-soluble drugs, such as the formulation of amorphous solid form, nanoparticles, microemulsions, solid dispersions, melt extrusion, salt formation and formation of water-soluble complexes. Among all, the most

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accepted approach is the lipid-based formulation approach [3,4]. Lipid-based formulations enhance the absorption by enhancing solubilization, prolonging gastric residence time, stimulating the intestinal lymphatic transport pathway, altering intestinal permeability, reduced activity of efflux transporters and reduced metabolism. Lipid-based formulations present a large range of optional systems such as solutions, suspensions, self-emulsifying

Nanoemulsions — Advances in Formulation, Characterization and Applications in Drug Delivery

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Nanoemulsions can be prepared by high- and low-energy methods. Both high-energy and lowenergy methods can produce stable nanoemulsions. High-pressure homogenizer or ultra‐ sound generator can be used for the preparation of nanoemulsion by high-energy emulsification method. Self emulsification and phase inversion methods-phase inversion temperature and phase inversion composition are low-energy methods for the preparation of nanoemulsions. Low-energy emulsification methods depend on the phase behaviour and properties of the constituents, and they utilize the stored energy of the system to form nano droplets. The emulsification can be brought about by changing the parameters such as temperature and composition, which would affect the hydrophilic lipophilic balance of the

This chapter focused on recent advances in the formulation, characterization and application of nanoemulsions in drug delivery. Nanoemulsion can be formulated for delivery of drugs through various routes. Nanoemulsions are well tolerated orally and on the skin and mucous membranes when used to deliver topically active drugs. As a result they are used as vehicles for drugs active against herpes labialis, fungal infections, bacterial infections, vaginitis, etc. Nanoemulsion globules can fuse with membranes of lipid-containing organisms facilitating penetration and transfer. Less amount of surfactant is required in nanoemulsions compared to other emulsion systems. This can increase the bioavailability of poorly soluble drugs since small particles easily cross the absorption membrane. Furthermore, very small size provides large surface area which eases the solubilization and penetration through the skin or epithelial

**2. Nanoemulsion based delivery system: types and properties**

Self-emulsifying formulations (SEFs) are mixtures of oil, surfactant, co-surfactant, and cosolvents (absence of external phase water) and forms a transparent isotropic solution, which emulsify under gentle agitation similar to those which would be encountered in gastro intestinal tract (GIT). It has been recognized that this formulation when administered orally undergo spontaneous emulsification in aqueous GI fluids [6]. This emulsified oil (triglycerides) stimulates bile secretion and drug containing oil droplets are further emulsified by bile salts. Lipid droplets are then metabolized by lipases and co lipases, secreted from the salivary gland, gastric mucosa and pancreas, which also hydrolyze the triglycerides into di-and monoglycer‐ ides and free fatty acids. Further, solubilization of these molecules occurs during the passage through the GI tract and eventually forms a range of emulsion droplets, vesicular structures

**2.1. Self emulsifying formulations (SEFs)**

systems and nanoemulsions.

system.

layer [5].

consisting of emulsified oil and water systems with mean droplet diameters ranging from 50 to 1000 nm. Usually, the average droplet size is between 100 and 500 nm and can exist as oil-inwater (o/w) or water-in-oil (w/o) form, where the core of the particle is either oil or water, respectively. Nanoemulsions (Figs. 1 and 2) are made from pharmaceutical surfactants that are generally regarded as safe (GRAS). The surfactant type and concentration in the aqueous phase are chosen to provide good stability against coalescence. Several types of oils- natural, semisynthetic and synthetic are used in the formulation of nanoemulsions. The capacity of nanoemulsions to dissolve large quantities of low soluble drugs along with their mutual compatibility and ability to protect the drugs from hydrolysis and enzymatic degradation make them ideal drug delivery vectors [1]. The major advantages of nanoemulsions as drug delivery

Nanoemulsions courtesy of the Chemical, Materials and Surfaces unit at SP Technical Research Institute of Sweden (former YKI, Institute for Surface Chemistry). Obtained via: http://www.vironova.com/nanoemulsions-casebody. Ac‐ cessed on April 27, 2014.

**Figure 1.** A silicate particle-stabilized oil in water nanoemulsion imaged using negative stain TEM (left panel) and cryo TEM (right panel). Nanoemulsions courtesy of the Chemical, Materials and Surfaces unit at SP Technical Research **Figure 1.** A silicate particle-stabilized oil in water nanoemulsion imaged using negative stain TEM (left panel) and cryo TEM (right panel).

**Figure 2.** Negative stain TEM image of a silicate particle-stabilized oil in water nanoemulsion. Obtained via: http:// www.vironova.com/nanoemulsions-casebody. Accessed on April 27, 2014.

accepted approach is the lipid-based formulation approach [3,4]. Lipid-based formulations enhance the absorption by enhancing solubilization, prolonging gastric residence time, stimulating the intestinal lymphatic transport pathway, altering intestinal permeability, reduced activity of efflux transporters and reduced metabolism. Lipid-based formulations present a large range of optional systems such as solutions, suspensions, self-emulsifying systems and nanoemulsions.

Nanoemulsions can be prepared by high- and low-energy methods. Both high-energy and lowenergy methods can produce stable nanoemulsions. High-pressure homogenizer or ultra‐ sound generator can be used for the preparation of nanoemulsion by high-energy emulsification method. Self emulsification and phase inversion methods-phase inversion temperature and phase inversion composition are low-energy methods for the preparation of nanoemulsions. Low-energy emulsification methods depend on the phase behaviour and properties of the constituents, and they utilize the stored energy of the system to form nano droplets. The emulsification can be brought about by changing the parameters such as temperature and composition, which would affect the hydrophilic lipophilic balance of the system.

This chapter focused on recent advances in the formulation, characterization and application of nanoemulsions in drug delivery. Nanoemulsion can be formulated for delivery of drugs through various routes. Nanoemulsions are well tolerated orally and on the skin and mucous membranes when used to deliver topically active drugs. As a result they are used as vehicles for drugs active against herpes labialis, fungal infections, bacterial infections, vaginitis, etc. Nanoemulsion globules can fuse with membranes of lipid-containing organisms facilitating penetration and transfer. Less amount of surfactant is required in nanoemulsions compared to other emulsion systems. This can increase the bioavailability of poorly soluble drugs since small particles easily cross the absorption membrane. Furthermore, very small size provides large surface area which eases the solubilization and penetration through the skin or epithelial layer [5].
