Gels are formed when a compound present in a solution self-assembles to form a highly cross-linked fibrillar network in which the solvent molecules remain entrapped. The resulting material has properties that are intermediate between those of liquids and solids. Usually, gels are classified according to the nature of the solvent involved.1, 2 Thus, hydrogels refer to gels formed in the presence of water, while organogels are those in which organic solvents are involved.
Many different types of compounds have been developed and used either as hydrogelators or as organogelators; according to the foods industry, natural and nonnatural polymers originally were tested for the formation of gels. Nevertheless, the use of low molecular weight gelators has gained increasing importance in recent years. Since low molecular weight compounds possess a well-defined structure, their properties including self-assembling behavior can be more easily studied, which allows for the more efficient design and fine-tuning of gelating agents. As a consequence, a large number of technological applications have recently been reported for gels formed either in water or organic solvents through the use of low molecular weight molecules.3 In particular, gel formulations are used as penetration enhancers for drug and cosmetic actives release. This is due to the fact that incorporating the active component in a gel matrix can control its release rate, increasing the application time and consequently, the corresponding activity.4
In this regard, there are several aspects that must be taken into consideration. First of all, topical application in the form of gel increases the contact time, thus favoring the action of the active principles. In addition, it limits the application to the specific desired area, reducing the side effects on other areas, i.e., local irritation. Finally, the occlusion of the active principle in a complex matrix can control the release rate of the active principles, and the capacity of the gelator molecules to interact with other compounds via supramolecular interactions can be used to regulate this capacity.
Three main properties can be used to define the efficiency of a given gelator: the minimum concentration of the compound in a given solvent at which the gel is formed; the solvents for which the compounds are able to act as the gelator; and the stability of the gel in the presence of external stimuli such as pressure, temperature and pH changes. In general, good gelators can act in concentrations as low as 1–5% w/w, or even lower. Hydrogelators and organogelators differ in that they usually possess different chemical structural motifs including specific groups such as amide, urea and carbamate. In the case of organogelators, most can act as such only for a limited number of solvents with related structures, e.g., toluene, dimethyl sulfoxide, N,N-dimethylformamide and methanol, and if one compound is a good gelator for alcohols, it is usually is not a good gelator for ethers. Hydrogelators, on the other hand, incorporate additional polar groups, e.g., carboxylic acids, hydroxy and amino, in their chemical structure, which increases their compatibility with water.
The stability of the gels formed in the presence of external stimuli is critical for practical applications, since gels provide the structure into which additional functionally active compounds are embedded. Thus, gels must be stable in the presence of active compounds as well as during the preparation conditions for the corresponding formula and its manipulation and use. In this regard, thermal stability is often a limiting factor. Gels are usually formed by heating a solvent in the presence of the gelator and upon cooling, the gel structure spontaneously forms in a reversible process. Accordingly, many gels maintain their properties only at temperatures lower than 50—60°C.