Carrageenan, when extracted from the appropriate seaweed source, is a yellow-brown to white colored, coarse to fine powder that is odorless and tasteless.
Nonproprietary Names USP-NF: Carrageenan
Chondrus extract; E407; Gelcarin; Genu; Grindsted; Hygum TP-1; Irish moss extract; Marine Colloids; SeaSpen PF; Viscarin.
Chemical Name and CAS Registry Number
- Carrageenan [9000-07-1]
- i-Carrageenan [9062-07-1]
- k-Carrageenan [11114-20-8]
- l-Carrageenan [9064-57-7]
Empirical Formula and Molecular Weight
The USP32–NF27 describes carrageenan as the hydrocolloid obtained by extraction with water or aqueous alkali from some members of the class Rhodophyceae (red seaweed). It consists chiefly of potassium, sodium, calcium, magnesium, and ammonium sulfate esters of galactose and 3, 6-anhydrogalactose copolymers. These hexoses are alternately linked at the a-1, 3 and b-1, 4 sites in the polymer.
Functional Category: Emulsifying agent; gel base; stabilizing agent; suspending agent; sustained-release agent; viscosity-increasing agent.
Applications in Pharmaceutical Formulation or Technology
Carrageenan is used in a variety of nonparenteral dosage forms, including suspensions (wet and reconstitutable), emulsions, gels, creams, lotions, eye drops, suppositories, tablets, and capsules. In suspension formulations, usually only the i-carrageenen and lcarrageenan fractions are used.
l-Carrageenan is generally used at levels of 0.7% w/v or less, and provides viscosity to the liquid. Carrageenan has been shown to mask the chalkiness of antacid suspensions when used as a suspending agent in these preparations. When used in concentrations of 0.1–0.5%, carrageenan gives stable emulsions. Carrageenan is used in hand lotions and creams to provide slip and improved ‘rub out’.
i-Carrageenan develops a shear-thinning thixotropic gel, which can be easily poured after shaking. When i-carrageenan is used, the presence of calcium ions is required for the gel network to become established. With pure i-carrageenan, about 0.4% w/v is required for most suspensions plus the addition of calcium. However, if SeaSpen PF is used, it must be at about 0.75% w/v level, although no additional calcium is required as this is already present in the product to control the rate of gelation.
Studies on the effect of carrageenan and other colloids on mucoadhesion of drugs to the oropharyngeal areas have shown that carrageenan had the greatest propensity for adhesion and can be used in formulations for oral and buccal drug delivery.
The application of carrageenan in topical gel bases has been examined, and the findings indicate that the use of carrageenan in these dosage forms is most likely to be dependent on the active drug, owing to the potential for ionic interactions. In the case of topical gels, a combination of i, k-, and lcarrageenans produces a spreadable gel with acceptable tactile sensation, resulting in drug release that is more likely to follow diffusion kinetics.
Incorporation of carrageenan into tablet matrices with various drugs and other excipients to alter release profiles has been studied, illustrating that the carrageenans have good tablet-binding properties.
Furthermore, the inclusion of calcium or potassium salts into the tablet creates a microenvironment for gelation to occur, which further controls drug release.
There have also been several references to the use of carrageenan in chewable tablets having a confectionary texture. This approach to creating a novel dosage form requires the use of both icarrageenan and k-carrageenan, to prevent moisture loss and texture changes that occur over time.
Carrageenan has been used for the microencapsulation of proteins and probiotic bacteria. Hydrogels have also been prepared by crosslinking with gelatin and k-carrageenan for oral delivery of probiotic bacteria.
It has also been used as beads in the preparation of controlled release systems. Hydrogel beads based on k-carrageenan and sodium alginate/chitosan are being systems.
k-Carrageenan is known as a novel pelletization aid in the manufacture of pellets by extrusion/spheronization and has the best pelletization behavior. l-Carrageenan is also able to nanoencapsulate drug molecules spontaneously, hence controlling drug release.
The presence of carrageenan induces the formation of smaller particles compared to those formed in the absence of polymer, and their average size depends on the nature and concentration of the polysaccharide used. Studies have shown that carrageenan compounds block infections by the herpes simplex virus; human cytomegalovirus; human papilloma virus; Sindbis virus; vesicular stomatitis virus; and HIV.
A combined k- and l-carrageenan formulation is currently being investigated as the active ingredient in a topical microbicide used to prevent the sexual transmission of HIV. In combination with chitosan, agar and polyvinyl pyrrolidone, carrageenan forms a water-insoluble complex which is able to absorb large amounts of body fluids, and is used as an effective wound dressing. Carrageenan is used in the preparation of hard and soft capsule shells. It is also used in toothpastes and cosmetic preparations such as conditioners and shampoos.
Method of Manufacture
The main species of seaweed from which carrageenan is manufactured are Eucheuma, Chondrus, and Gigartina. The weed is dried quickly to prevent degradation, and is then baled for shipment to processing facilities. The seaweed is repeatedly washed to remove gross impurities such as sand, salt, and marine life, and then undergoes a hot alkali extraction process, releasing the carrageenan from the cell.
Once it is in a hot solution, carrageenan undergoes clarification and concentration in solution and is converted to powder. Three processes can be used to remove the carrageenan from solution. The first is a ‘freeze–thaw’ technique. The solution is gelled with various salts, then the gels are frozen. Upon thawing, the water is removed and the resultant mass, primarily carrageenan and salt, is ground to the desired particle size.
The second method, referred to as the ‘alcohol precipitation method’ takes the concentrated solution of carrageenan and places it in alcohol. This causes the carrageenan to precipitate out of solution. The co-solvents are evaporated and the precipitated carrageenan is dried and ground to the desired particle size.
The third method is the ‘KCl precipitation’ process, where after hot extraction, the filtrate is evaporated to reduce the filtrate volume. The filtrate is then extruded through spinnerets into a cold 1.0–1.5% solution of potassium chloride. The resulting gel threads are washed with KCl solution and are pressed, dried and milled to carrageenan powder.
Commercial carrageenan is usually standardized by blending different batches of carrageenan and adding sugar or salt to obtain the desired gelling or thickening properties.