Common Gelling Agents
There are many gelling agents. Some of the common ones are acacia, alginic acid, bentonite, Carbopols® (now known as carbomers), carboxymethyl cellulose, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, magnesium aluminum silicate (Veegum®), methylcellulose, poloxamers (Pluronics®), polyvinyl alcohol, sodium alginate, tragacanth, and xanthan gum. Though each gelling agent has some unique properties, there are some generalizations that can be made:
- If the gelling agent is added to the dispersing medium in a haphazard manner, there is a tendency for the agent to "clump." The outer molecules of the gelling agent contact the medium first and hydrate, forming a surface layer that is more difficult for the medium to penetrate. The clumps will ultimately hydrate, but it will take more time. A much more efficient manner is to sieve the agents onto the surface of the medium a little at a time as the medium is stirred. Using glycerin as a wetting agent will sometimes minimize clump formation.
- Some gelling agents are more soluble in cold water than in hot water. Methylcellulose and poloxamers have better solubility in cold water while bentonite, gelatin, and sodium carboxymethyl cellulose are more soluble in hot water. Carbomers, tragacanth, and alginic acid gels are made with tepid water.
- Some gelling agents (carbomers) require a "neutralizer" or a pH adjusting chemical to create the gel after the gelling agent has been wetted in the dispersing medium.
- Most gelling agents require 24 to 48 hours to completely hydrate and reach maximum viscosity and clarity.
- Gelling agents are used concentrations of 0.5% to 10%, depending on the agent.
- It is easier to add the active drug before the gel is formed if the drug doesn't interfere with the gel formation.
- Only Carbopol® 934P, methylcellulose, hydroxypropyl methylcellulose, and sodium carboxymethyl cellulose are recommended for oral administration.
Carbomer is a generic name for a family of polymers known as Carbopol®. Carbopols® were first used in the mid 1950s. As a group, they are dry powders, which have high bulk densities and form acidic aqueous solutions(pH around 3.0). They thicken at higher pHs (around 5 or 6). They will also swell in aqueous solution of that pH to as much as 1000 times their original volume. Their solutions range in viscosity from 0 to 80,000 centipoise (cps). Some examples of this group of gelling agents are:
||3,000 - 7,000
- Effective in low concentrations.
- Will provide a low viscosity formulation.
||30,500 - 39,400
- Effective in thick formulations such as emulsions, suspensions, sustained-release formulations, transdermals, and topicals.
- Forms clear gels with water.
||29,400 - 39,400
- Same properties as 934, but intended for pharmaceutical formulations.
- "P" = highly purified product
||40,000 - 60,000
- Effective in thick formulations.
- Very good clarity in water or hydroalcoholic topical gels.
- Forms clear gels with hydroalcoholic systems.
||4,000 - 11,000
- Produces low viscosity gels.
- Very good clarity.
* 0.5% solution, pH 7.5
Carbomer polymers are best introduced into water by slowly sprinkling a sieved powder into the vortex created by rapid stirring. This should prevent clumping. Once all of the powder has been added, the stirring speed should be reduced to decrease the possibility of entrapping air bubbles in the formulation.
As mentioned, when the carbomer is dispersed, the solution will have a low pH. A neutralizer is added to increase the pH and cause the dispersion to thicken and gel. Some neutralizing agents are sodium hydroxide, potassium hydroxide, and triethanolamine. If inorganic bases are used to neutralize the solution, a stable water soluble gel is formed. If triethanolamine is used, the gel can tolerate high alcohol concentrations. The viscosity of the gel can be further manipulated by propylene glycol and glycerin (to increase viscosity) or by adding electrolytes (to decrease viscosity).
The cellulose derivatives (methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxymethyl cellulose) are commonly used. There are some commonalties in these compounds, and each one has their unique properties.