Carrageenan:A Naturally Occurring Routinely Used Excipient

Shailesh Prajapati

Carrageenan is a wholly natural ingredient obtained from certain species of the red seaweed, class Rhodophyceae . Popular sources for carrageenan are the Chondrus Crispus, Eucheuma Cottonii and Eucheuma Spinosum species.

Commercial carrageenans are available as stable sodium, potassium, and calcium salts or, most generally, as a mixture of these. Carrageenan has unique properties, which cannot be replaced by other food grade, safe and non-toxic materials. Carrageenans are far more widely used than agar as emulsifiers/stabilizers in numerous foods, especially milk based products. It is estimated that the average human consumption of carrageenans in the United States is 250 milligrams (0.01 ounce) a day. Kappa, iota and lambda carrageenans differ in gelling and milk reactivity and are the three most widely used types in commercial products.

Introduction

Following World War II, expansion in the food industry coupled with the need for convenience foods and an increased awareness of quality, produced a demand for stabilizers capable of modifying and controlling texture and rheology. Development of carrageenan and the harvesting and farming of the raw seaweeds sent hand in hand with these demands. An intimate relationship quickly developed between the food and stabilizer industries.

Figure 1: Carrageenan consists of alternating 3-linked-β-D-galactopyranose and 4-linked-α-D-galactopyranose units.

Carrageenan is a wholly natural ingredient obtained from certain species of the red seaweed, class Rhodophyceae ^1,2 . Popular sources for carrageenan are the Chondrus Crispus, Eucheuma Cottonii and Eucheuma Spinosum species. The Chondrus Crispus specie grows mainly in cold-water territories such as the northern coasts of the Atlantic while the Eucheuma species are abundantly found in temperate climates like the Philippines . The Philippines has successfully launched and maintained numerous Eucheuma Cottonii and Eucheuma Spinosum seaweed farms providing ample supply and good quality to meet the growing demand. It is generally considered a high-molecular-weight linear polysaccharide. Chemically, it comprises repeating galactose units and 3,6-anhydrogalactose (3,6-AG), sulfated and non-sulfated, joined by alternating α (1-)-and β (1-4)-glycosidic linkages ^3,4 . Commercial carrageenans are available as stable sodium, potassium, and calcium salts or, most generally, as a mixture of these. The associated cations together with the conformation of the sugar units in the polymer chain determine the physical properties of the carrageenans. Carrageenans can be produced via a variety of process techniques; alcohol extraction, potassium chloride gel press or extracted with various alkalis. The process technique is important because it influences the gel characteristics.

Carrageenans are used commercially as thickening, suspending, and gelling agents ⁵ . Typical applications are as a thickener or ‘binder’ in toothpaste, a suspending agent for cocoa in chocolate milk, and a gelling agent for milk puddings, water-gel deserts, and air-freshener gels.

Types Of Carrageen

The Three Basic Types of Carrageenan 

1. Kappa carrageenan binds water to form strong, rigid gels. Potassium salts are essential in order to form this firm gel structure. As the level of potassium is increased, the resulting gel structure becomes tightly aggregated and may cause syneresis (moisture on the gel surface).

Figure 2: Kappa carrageenan

2. Iota carrageenan also binds water, but forms a dry, elastic gel, especially in the presence of calcium salts. The divalent calcium ions help form bonds between the carrageenan molecules to form helices. The 2-sulfate group on the outside of the iota carrageenan molecule does not allow the helices to aggregate to the same extent as kappa carrageenan, but form additional bonds through calcium interactions. The gels are more elastic, dry and provide excellent freeze/thaw stability.

Figure 2: Iota carrageenan         

3. Lambda carrageenan is highly sulfated and therefore less likely to form a gel structure. The ester sulfate distribution of lambda carrageenan is randomly distributed on the molecule. This prevents gelation and promotes viscous solutions. Lambda carrageenan is primarily used to thicken liquids and modify the texture of foods.

Figure 2: Lamda carrageenan

Comparative properties of types of carrageenan: -

The primary differences which influence the properties of kappa, iota and lambda carrageenan are the number and position of the ester sulfate groups on the repeating galactose units ⁶ . Higher levels of ester sulfate lower the solubility temperature of the carrageenan and produce lower strength gels, or contribute to gel inhibition (lambda carrageenan).

General Properties

Solubilization & Gelation

Carrageenan has to be dispersed well before its solubilization to avoid the formation of lumps and to obtain its complete functionality. Carrageenan should be premixed with other dry ingredients such as sugar or salts, adding the product slowly into cold liquid with agitation.

All carrageenan are dispersible in cold water, and when heated above 80ºC they are completely dissolved. During cooling process Kappa and Iota carrageenan form double helix molecular structures cross-linked by potassium and calcium ions, forming a tridimensional gel-type network.

Synergies

Kappa I and Kappa II type carrageenan have a synergetic behavior with certain galactomannans and glucomannans, such as Locust Bean Gum and Konjac Gum. This interaction produces harder and more elastic gel with less syneresis.
Iota carrageenan has a positive interaction with starch. This interaction produces an increase in the viscosity of aqueous solutions.

pH Stability

Carrageenan solutions and gels are stable at neutral and slightly acid system. The combination of elevated temperature and acid conditions will produce hydrolysis of carrageenan resulting in a loss of viscosity and/or gel strength.
In acid systems (pH < 3.7), it is advisable to add carrageenan at the latest possible stage during processing, and cool down the solution very quickly. Once the gel is formed, this effect is not observed.

Rheology

Iota and kappa II carrageenan solutions show a thixotropic behavior in solution and gel states. Pumping, shear and agitation will destroy the structure formed, but it will be reset once the deformation is removed.

Interaction with proteins

Kappa II and Kappa I carrageenan have strong interaction with milk proteins, being able to form very firm gels at very low concentrations. This synergism is given by the direct interaction between carrageenan and k-casein. This interaction takes place in a wide range of pH and is strengthened by cations.

Interaction with salts

Kappa I and Kappa II carrageenan increase the hardness, brittleness, gelation and melting temperatures of their gels in water with the addition of potassium and calcium ions.

Sodium and potassium salts of polyphosphates and citrates enhance solubility of carrageenan in cold and hot solutions and reduce their viscosity due to divalent cations chelation.

Functional Properties Of Carrageenans

Gelling agent

Kappa I, Kappa II and Iota carrageenans produce stable gels in water at room temperature, without refrigeration. Depending on the combinations of different carrageenan fractions, a broad variety of gel textures can be obtained, from strong and brittle to very elastic.

Water holding agent

Kappa I, Kappa II and Iota carrageenans are excellent water holding agents due to their high capacity to bind water and form gels. This capacity allows them to retain the natural water of products, especially when subjected to thermal processing and to increase their processing yield.

Suspending agent

Kappa II and Kappa I, at very low concentrations form an imperceptible weak gel in milk or water allowing solids to remain suspended in solution without providing much viscosity to the system.

Thickening agent

Lambda carrageenan may act as thickening agent in cold and hot systems. Iota and Sodium Kappa II carrageenans are also widely used as thickening agents in products that undergo thermal processing.

Stabilizing agent

Carrageenans are able to stabilize emulsions because of their high capacity to form matrixes and their strong electrostatic interaction. Due to the high specificity of carrageenan, it is the only agent capable to stabilize without modifying the system texture.

Application Of Carrageenan

Food application:

Non-Food Application:

Petfood

Canned meat and fish:               Gelling and stabilizing agent.  Moist, solid

                                                petfood -binder.

Toothpaste:                              Stabilizer.

Air freshener:                            Gelling agent.

Pharmaceutical Application

Drug delivery systems :

The trapped material in tablet form used to administer drugs orally and also it can be used in both topical bases ⁷ and suppository bases ⁸ .

Wound dressings:

Insoluble carrageenan- chitosan fibers can be spun with active pharmaceutical agents trapped within the fibers. The resulting systems, although water insoluble, will absorb considerable quantities of body fluids enabling wounds to be kept clean and dry speeding the healing process.

Cosmetics:

The unique interactions between carrageenan and polyols can be exploited to control textural properties of any formulation or preparation containing polyols.

Hand Lotions and Shampoos:

In hand lotions and shampoos, carrageenan not only thickens the product but also promotes healthy skin and hair. In addition, carrageenan is a natural product and can be incorporated into formulations, which rely on natural ingredients for their promotion.

Contraceptive gels:

Existing products suffer from a lack of gel structure and typically drain from the vagina causing embarrassment and reducing efficacy. Carrageenan gels in contrast, can be tailored to have rapid re-healing characteristics ideally suited to maintaining protection during intercourse. There is evidence that molecule such as carrageenan complex strongly with the protein coat of the HIV virus suggesting that contraceptive gels made from carrageenan may reduce the probability of infection.

Dentifrice:

Carrageenan stabilizes toothpaste preparations by a combination of viscosity, continuous phase gel formation and specific interactions with the abrasive. The continuous phase gel matrix enhances viscosity stabilization and provides emulsion stability by trapping abrasive and flavor oil micelles within the gel matrix. The gel structure also imparts a desirable short texture to the toothpaste providing a clean (non- stringy) break on extrusion from the tube or pump. Specific interactions between carrageenan and the surface of abrasives both disperses and stabilizes the solids preventing hardening, caking and drying out. Other binders that are now available have one or the other of the properties of carrageenan but not the combination which makes carrageenan unique in the dentifrice industry. Coupled with this is the fact that carrageenan is stable to enzymes either and can be used in areas of the world where binders such as CMC cannot. It does not contain enzymes either and can safely be used in combination with CMC. Xanthan gum, an expensive binder for toothpaste preparations, contain enzymes which attack CMC rendering it impossible to use them in combination

Humidity Control:

The concept of hermetically sealed package is somewhat of a misnomer since almost all commercially produced leak to some extent. For most purposes, the loss of moisture is unimportant but there are some applications where this is not the case as, for example, in advanced instant film packages. When it is necessary to control the humidity within a package, a small nugget of carrageenan gel can be used. Moisture lost by leakage is replaced at the expense of the gel, which merely shrinks in size.

Biotechnology (Cell Immobilization):

The area of immobilized cells and organelles has expanded very fast. Many new techniques for the preparation of immobilized cells have been developed during the past decade and a broad spectrum of applications has been investigated. Increasingly more gentle immobilization procedures have evolved to the point when it now seems possible to hold any cell structure and keep it alive and viable. Carrageenan is especially useful for trapping seeds, cells and microorganisms with or without nutrients and other active materials. The immobilized seed, cell moisture during germination and critical stages of development. One of the chief advantages of carrageenan over the gelling temperature, well within the tolerance range of the organism being immobilize. Enzyme activity of immobilized cells entrapped in carrageenan is generally high.

The applications for cell immobilization techniques are varied in the extreme and can range from ethanol production as a potential source of liquid fuel to the prolonged survival of transplanted islets of Langerhans encapsulted in biocompatible membranes.

Safety Aspect Of Carrageenan

The WHO (world health organization) has set an acceptable daily intake of carrageenan of “ not specified” since the total daily intake (arising from it’s use at level necessary to achieve the desire effect and from its background in food) was not consider to represent a hazard to health ⁹ . In the UK food advisory committee has recommend that carrageenan should not be used as an additive for infants’ formulation ^{10, 11} .

Conclusion

Carrageenan is a wholly natural ingredient obtained from certain species of the red seaweed, class Rhodophyceae . Carrageenan has unique properties, which cannot be replaced by other food grade, safe and non-toxic materials. The producers of quality carrageenan products look forward to assured growing markets throughout the world displacing carrageenan. Its use in industrialized countries is well established and will rapidly spread into third world countries as their economies and demands for quality foods, cosmetics and industrial goods grow.

References

1. Kalia A.N., Text book of industrial Pharmacognosy, 2005, pp 217
2. Trease and Evans Pharmacognosy, 2002, pp 206
3. Paul C. S., Richard L.M., McGraw-Hill Encyclopedia of science and Technology, 7 ^th edition, vol-3, 1992, pp 285
4. Remington The science and practice of pharmacy, 20 ^th edition, vol-1, 2000, pp 1031.
5. Kar Ashutosh, Pharmacognosy and Pharmacobiotechnology, 2003, pp 134
6. Kennedy, J.F., White, C.A., Bioactive Carbohydrates in Chemistry, Biochemistry and Biology, Ellis Horwood, Chichester, U.K, 1983, pp 163.
7. Lev R, Long R, Mallonga L, Schnaram R, Reily W., Evaluation of Carrageenan as Base For Topical Gels, Pharm. Res., 1997,14(11), pp 42.
8. Lui Y., Schnaram R, Reily W., Evaluation of Carrageenan as Suppository Base, Pharm. Res., 1997,14(11), pp 41.
9. FAD/WHO Evaluation of Certain Food Additive abd Contaminants: Twenty Eight Report of the Joint FAD/WHO Expert Committee on Food Additives, Tech Rep Ser Wld Health Org, 1984, pp 710
10. MAFF, Food Advisory Committee: Report on The Review of the Use of Additive in Foods Specially Prepared For Infants and Young Children, Fdac/REP/12, London , HMSO, 1992.
11. Review of harmful gastrointestinal effects of carrageenan in animal experiments J. K. Tobacman. Environ Health Perspect. 2001, 109(10), pp 983.

About Authors:

S.T. Prajapati, A.K. Patel, L.D. Patel*,

Shri Sarvajanik pharamacy college, Mehsana, Gujarat, India

*DDIT pharmacy college, Nadiad, Gujarat, India

Mr. Shailesh Prajapati is working as an Asst. Professor in Pharmaceutical Technology Department at Shri Sarvajanik Pharmacy College, Mehsana, India. He had completed his MPharm in Pharmaceutics from L.M.Collge of Pharmacy, Gujarat University, Ahmedabad. He has presented research papers at international and national level conferences, and his core interest includes research of novel floating drug delivery systems.

For correspondence

Prajapati Shailesh T. , Asst. Professor , Department of pharmaceutics. Shri Sarvajanik pharmacy College , Near Arvind baug, Mehsna, Gujarat-384 001, India
E-mail: stprajapati@gmail.com , Phone: +91 2762 24771, Fax:  +91 2762 24772

Dr. Laxmanbhai Patel is currently principal and HOD of the Department of Pharmaceutics & Pharmaceutical Technology at DDIT Pharmacy college, Nadiad. He earned his PhD in Pharmaceutics & Pharmaceutical Technology from Gujarat University. Dr. Patel has 25 years of academic and research experience and has 40 national and intentional research papers to his credit. He is an approved PhD guide at Gujarat university, Hemchandrachayra North Gujarat University, Patan and Saurashtra university

Mr. Amit Patel is currently working as a Lecturer in Pharmaceutical Technology at He Shri Sarvajanik Pharmacy College, Mehsana, India. He has earned his MPharm in Pharmaceutical Technology from M.S. University, Baroda. His current research interests is development of directly compressible excipients.