The viscous and elastic nature of LOs follows the Maxwell model of viscoelasticity (Toshiyuki et al. 2003; Shikata et al. 2003). LOs are the three-dimensional structures formed as a result of physical interactions of lecithin molecules with each other. LOs show an elastic property at low shear rate. As the shear rate increases, the physical interactions among lecithin molecules start getting weak, and thereby the three-dimensional fibrous structure of LOs is distorted. Finally, the shear stress reaches its threshold and destroys the LOs’ structure. This behavior is termed as plastic flow behavior (Abdallah et al. 2000). The viscoelastic behavior of LOs depends on the concentration of lecithin and the type of organic solvent (precisely fatty acid ester) used. The higher the lecithin concentration, the higher is the viscosity (Schurtenberger et al. 1989). The long-chain fatty acid esters, such as isopropyl palmitate or cetearyl octanoate, produce LOs with high viscosity, whereas short-chain esters, such as ethyl and propyl acetate, produce LOs of relatively lesser viscosity. It is worthwhile to note that LOs can also be prepared by utilizing mixtures of solvents rather than using a single solvent. Using a blend of organic solvents, we can tailor the viscoelastic properties of LOs based on our needs. Nastruzzi et al. (1994) has developed LOs using a combination of organic solvents and investigated its effect on the viscoelastic properties of LOs. The viscosity of LOs has an impact on the release profile of the drug encapsulated into LOs. In general, the higher the viscosity, the slower is the release of the drug (Shchipunov and Shumilina 1995; Kumar and Katare 2005). Also, medicated LOs are reported to have slightly lesser viscosity than placebo LOs of similar composition (Shaikh et al. 2009; Nastruzzi and Gambari 1994).

The LOs when viewed under polarized light appear as a dark matrix. This is because the isotropic nature of organogels does not cause passage of polarized light through the matrix. This property of organogels is termed as non-birefringence (Kantaria et al. 1999; Nasseri et al. 2003). Optically, LOs are transparent and provide the benefit of visual inspection so that the presence of any particulate matter can be easily recognized (Kumar and Katare 2005).

Heating above critical temperature causes LOs to convert from gel state to sol state (Fig. 21.2). The temperature at which sol-gel transition takes place is called as gelation temperature. The gelation temperature varies depending on the solvent system used when preparing LOs. The gel-sol transition in LOs occurs when increased thermal energy within LOs disrupts physical interactions between lecithin molecules, and subsequent cooling of hot LOs causes regain of physical interaction between lecithin molecules which results in sol-gel transition (Avramiotis et al. 2007). The gelation temperature can be determined visibly. It is essential to determine the gelation temperature of the LOs containing drugs as it serves as a guide for recommending storage conditions for drug-loaded medicated LOs (Díaz et al. 2008; Dasgupta et al. 2009; Guenet 2006).

Lecithin is an important component of all living cells, and it is recognized by the Food and Drug Administration (FDA) as Generally Regarded as Safe (GRAS) (21 CFR 184, 1400). Compatibility studies with human skin revealed that topical use of LOs is safe (Dreher et al. 1997; Shchipunov et al. 2001; Schurtenberger et al. 1990). Vehicles (organic solvents, such as fatty acid esters, e.g., isopropyl myristate, ethyl oleate) used for preparing LOs are also GRAS excipients. LOs are moisture insensitive, and due to their organic nature, they resist microbial contamination. Thermodynamic stability, ease of preparation and scale-up, easier quality monitoring, and enhanced topical performance along with biocompatibility and safety upon applications for a prolonged period make the organogels a vehicle of choice for dermal and transdermal drug delivery.

Lecithin is a trivial name for 1, 2-diacyl-sn-3-phosphocholine. It belongs to a biologically essential class of substances termed phosphoglycerides or phospholipids. Lecithin is a complex mixture of acetone-insoluble phosphatides, which mainly consist of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol combined with different amounts of other substances such as triglycerides and fatty acids (Reynolds 1996). The main sources of lecithin are soya beans and egg yolk. Lecithin varies greatly in its physical form, from viscous semiliquid to powder depending on the content of free fatty acids. It may also vary in color from brown to light yellow depending on whether it is bleached or unbleached (Wade et al. 1994). Lecithin is commercially available on the market under trade name of Epikuron (Lucas Meyer, Hamburg, Germany), Lipoid S100 (Lipoid GmbH, Ludwigshafen, Germany), and Capcithin (Lucas Meyer, Hamburg, Germany), which are derived and purified from either soya bean or eggs. The desired gelation in organic solvent occurs only when the lecithin contains more than 95 % phosphatidylcholine and is free from fat as well as moisture. Lecithin is a multifunctional surface-active agent. The lecithin molecule consists of two portions: the nonpolar tail (fatty acid portion) and the polar head (phosphoric acid portion). Because of these two aspects, lecithin molecules arrange themselves at the boundary between immiscible liquids such as oil and water. This arrangement reduces the interfacial tension between oil and water and makes relatively stable emulsions (Scartazzini et al. 1988). Its unique lipid molecular structure performs versatile functions. It has a wide variety of roles in pharmaceuticals, cosmetics, and food industries as an emulsifier, viscosity modifier, stabilizer, and solubilizer and penetration enhancer (Szuhaj 1989). They form the lipid matrix of biological membrane and play a key role in the cellular metabolism (Hanahan 1997). Due to its biocompatibility, it is widely used in human and animal food, medicine, cosmetics, and other various industrial applications (Wendel 1995). No systematic research has been done till date in order to investigate the effect of unsaturation in phospholipids on organogelling ability. However, it has been reported that unsaturation in phospholipid molecules affect the nature of self-assembly in which the phospholipid molecules associate and form the microstructures. The property of unsaturation can be interpreted in terms of the degree of hydration of phospholipid molecules that it provides. Unlike saturated hydrogenated phospholipids, unsaturation in phospholipid molecules would result in better hydration of the polar head group, thereby increasing the area per lipid polar head group. Hence, a larger area-to-volume ratio would favorably alter the spontaneous curvature of lipid monomers for the formation of micelles and subsequently their self-assembly to form the micellar network (Shchipunov 2001).

Organic solvent plays a vital role in organogels by providing the desired solvent action for the drug (hydrophobic) as well as for lecithin (Kumar and Katare 2005; Moore 1982; Sato et al. 1988). More than 50 organic solvents have been reported to form organogels with water as an aqueous phase. Among them, there are linear, branched, and cyclic alkanes; ethers and esters; fatty acids; and amines. Specific examples include ethyl laureate, ethyl myristate, isopropyl palmitate, cyclopentane, cyclooctane, trans-decalin, trans- pinane, n-pentane, n-hexane, n-hexadecane, and tripropylamine. Among these, the fatty acid esters have been widely used for LO formation (due to better skin feel), but structural investigations have only been performed on hydrocarbons (such as isooctane, cyclohexane). Natural oils including soya bean oil, sunflower oil, rapeseed oil, and mustard oil are proposed as potentially useful organic solvents for preparing LOs (Shchipunov 2001).

The third component, a polar agent, acts as a structure forming and stabilizing agent. A series of polar solvents have been studied in order to check their suitability for producing the thickening effect on hydrocarbon and fatty acid ester solutions of lecithin. Water has been used extensively as a polar solvent for organogel formation. However, it has been established that glycerol, formamide, and ethylene glycol have the ability to induce gelation. The gel-forming ability of the polar solvent is governed by its physicochemical properties (Shchipunov and Shumilina 1995, 1996; Shchipunov and Hoffmann 1998). The ability to promote thickening of lecithin solutions has been correlated with the polarity of the solvent used for preparing LOs. This correlation is particularly pronounced in the series of structurally related solvents such as glycerol and ethylene glycol. In a proposed model of organogels, the solvent molecules bridge phosphate groups of neighboring lipid molecules, allowing their association into tubular aggregates through an extensive ribbonlike hydrogen bonding network (Shchipunov 2001). Figure 21.3 depicts schematic diagram of the preparation of LOs.

It is important to understand that LOs cannot be formed by random mixing of lecithin, an organic solvent and polar solvent. It depends on the mixing of a fixed quantity of these three components. Selection of suitable amounts of these three components can be done by making use of the pseudo ternary phase diagram. A detailed description on how to estimate the determination of the required amount of lecithin/water/organic solvent is described in the next section.