Gels are semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle, which has been thickened with a gelling agent. Gels can be a single phase or a biphasic system.
• Single-phase gels use high molecular weight hydrophilic polymers as gelling agents. Examples of such polymers include carbomers (cross-linked acrylic acid polymers). These gels are considered to be one-phase systems because no definite boundaries exist between the dispersed macromolecules and the liquid.
• Biphasic gels could contain a gelatinous, cross-linked precipitate of one substance in the aqueous phase. For example, magma or milk of magnesia consists of a gelatinous precipitate of magnesium hydroxide.
Gelling agents in single-phase gels could be (a) synthetic macromolecules, for example, carbomer 934; (b) cellulose derivatives, such as carboxymethylcellulose; and (c) natural gums, for example, tragacanth. Carbomers are high molecular weight water-soluble polymers of acrylic acid
cross-linked with allyl ethers of sucrose and/or pentaerythritol. Their viscosity depends on their polymeric composition. They are used as gelling agents at concentrations of 0.5%–2% w/w in water.
In addition to the gelling agent and water, gels may also contain a drug substance, cosolvents (such as alcohol and/or propylene glycol), antimicrobial preservatives (such as methylparaben and propylparaben, or chlorhexidine gluconate), and stabilizers (such as the chelating agent edetate disodium).
Gels can be classified based on their gelling agent as inorganic and organic. Inorganic gels use precipitates of inorganic salts, such as magnesium hydroxide, as gelling agents, whereas organic gels generally use a carbon-based hydrophilic polymer. Inorganic gels are generally two-phase systems, whereas organic gels are generally single-phase systems.
Based on the solvent phase of the gels, they may be classified as hydrogels or organogels. Hydrogels contain water as the main continuous phase solvent, whereas organogels may contain an organic liquid. Hydrogels contain significant amounts of water but remain as water insoluble.
The diffusion rate of a drug from a gel depends on the physical structure of the polymer network and its chemical nature. If the gel is highly hydrated, diffusion occurs through the pores. In gels of lower hydration, the drug dissolves in the polymer and is transported between the chains. Polymer cross-linking increases the hydrophobicity of a gel and reduces the diffusion rate of the drug.
Gels typically display non-Newtonian flow characteristics, that is, they show a nonlinear relationship between shear stress and strain rate, which can also be time dependent. Depending on their flow characteristics, gels may be shear thinning (pseudoplastic, i.e., viscosity decreases and flow increases on agitation), shear thickening (dilatant, i.e., viscosity increases and flow decreases on agitation), or thixotropic (e.g., requires decreasing stress to maintain a constant strain rate over time; or, in other words, viscosity decreases and flow increases over time under the same agitation rate).
Inorganic gels consist of floccules of small particles, as found in aluminum hydroxide gel or bentonite magma. Such gels may be thixotropic, displaying higher viscosity and a semisolid state on standing and becoming low viscosity liquids on agitation.
Jellies are semisolid gels of intertwining hydrophilic polymers that form a structurally coherent matrix and contain a high proportion of liquid, usually water, hydrogen bonded and associated with the hydrophilic polymer chains. Adding a thickening agent to an aqueous solution of a drug substance forms a jelly.
The thickening agent could be natural gums, such as alginates, tragacanth, and pectin or synthetic derivatives of natural substances such as sodium carboxymethyl cellulose (CMC) and methyl cellulose (MC). The resultant product is usually a clear and uniform semisolid. Jellies, being aqueous, are prone to bacterial growth. Thus, antimicrobials are usually added as preservatives.