Section 13

Carrageenan
By Dr. William A. Bubnis

Table of Contents
Carrageenan ..................................................................................................................................1
Table of Contents.......................................................................................................................1
Current FMC Products...................................................................................................................2
Gelcarin GP-911.......................................................................................................................2
Gelcarin GP-812.......................................................................................................................2
Gelcarin GP-379.......................................................................................................................2
Viscarin GP-109 .......................................................................................................................2
Viscarin GP-209 .......................................................................................................................2
Viscarin GP-328 .......................................................................................................................3
SeaSpen PF .............................................................................................................................3
General Introduction ......................................................................................................................3
History............................................................................................................................................3
Carrageenan Source......................................................................................................................4
Processing .....................................................................................................................................7
Processing Effect on Carrageenan Properties ..........................................................................8
Molecular Structure .....................................................................................................................10
Properties.....................................................................................................................................12
Solubility ..................................................................................................................................12
Gelation....................................................................................................................................14
Gel Texture Modification..........................................................................................................18
Effect of Cation ........................................................................................................................19
Synergism with other Gums ....................................................................................................22
Effect of pH..............................................................................................................................24
Rheology..................................................................................................................................24
Protein Reactivity.....................................................................................................................28
Dispersion of Carrageenan ......................................................................................................29
Applications .................................................................................................................................30
Soft Chewable Delivery System ..............................................................................................30
Suspensions ............................................................................................................................30
Reconstitutable Suspensions ..................................................................................................30
Controlled Release ..................................................................................................................31
Encapsulation and Entrapment ...............................................................................................32
Emulsion Stabilization..............................................................................................................32
Other Applications ...................................................................................................................32
Product Summary........................................................................................................................33
References ...................................................................................................................................34

1
 Current FMC Products
Gelcarin GP-911 Carrageenan (Kappa)
This product is a moderately low potassium
salt of kappa carrageenan. It displays partial
solubility in cold water and full solubility in
hot. When used at levels of 0.5 - 2.0%,
brittle, firm gels are produced. Resultant
gels will display no freeze/thaw stability,
syneresis, and will not reheal themselves
after being sheared. Gel strength can be
increased with the addition of potassium
ions. This product will also display synergis-
tic activity with other polysaccharide gums.
Gelcarin GP-911 displays protein and polyol
reactivity, and can be used in encapsulation,
chewable tablet, soft chewable gel delivery,
and film formation applications.
Gelcarin GP-812 Carrageenan (Kappa)
This product is a moderate potassium salt
kappa carrageenan. It swells in cold water
and displays full solubility in hot. When
used at levels of 0.3 - 1.0%, strong, brittle
gels result. These gels display increased
syneresis over Gelcarin GP-911. Gel
strength can be further increased with the
addition of potassium ions, and synergistic
activity with other polysaccharide gums
is observed. Gelcarin GP-812 displays
protein and polyol reactivity, and can
be used in encapsulation, chewable
tablet, and film formation applications.
Gelcarin GP-379 Carrageenan (Iota)
This product is a moderate calcium salt of
iota carrageenan. It swells in cold water and
displays full solubility in hot. When used at
levels of 0.3 - 1.0%, thixotropic or elastic
gels of medium gel strength are produced.
Resultant gels will display no syneresis,
freeze/thaw stability, and will reheal them-
2
selves after being sheared. Gel strength can
be increased with the addition of calcium
ions. This product is not synergistic with
other polysaccharide gums. Gelcarin GP-379
displays protein and polyol reactivity, and
can be used in cream, emulsion, suspension,
soft chewable gel delivery, controlled release
tablet, low pH, taste masking, and film
formation applications.
Viscarin GP-109 Carrageenan (Lambda)
This product is a non-gelling carrageenan.
It displays partial solubility in cold water
and full solubility in hot. When used at
levels of 0.1 - 1.0%, solutions of medium
viscosity are produced. Lambda carrageenan
has moderate salt tolerance, displays
freeze/thaw stability, and does not exhibit
synergistic activity with other polysaccharide
gums. Viscarin GP-109 displays protein
and polyol reactivity, and can be used in
cream, lotion, suspension, controlled
release, taste masking, and film formation
applications.
Viscarin GP-209 Carrageenan (Lambda)
This product is a non-gelling carrageenan.
It displays partial solubility in cold water
and full solubility in hot. When used at
levels of 0.1 - 1.0%, solutions of high
viscosity are produced. Lambda carrageenan
has moderate salt tolerance, displays
freeze/thaw stability, and does not exhibit
synergistic activity with other polysaccharide
gums. Viscarin GP-209 displays protein
and polyol reactivity, and can be used in
cream, lotion, suspension, controlled
release, taste masking, and film formation
applications.
Viscarin GP-328 Carrageenan
(Kappa/Lambda)
This product is a weak-gelling carrageenan.
It swells in cold water and displays full
solubility in hot. When used at levels of 0.7 -
1.2%, solutions of medium to high viscosity
with a weak gel structure are produced. The
product displays freeze/thaw stability, and
does not exhibit synergistic activity with
other polysaccharide gums. Viscarin GP-328
displays protein and polyol reactivity, and
can be used in cream, lotion, emulsion,
suspension, controlled release, taste
masking, and film formation applications.
SeaSpen PF Carrageenan (Iota)
This product is a readily dispersible salt of
iota carrageenan. The product displays cold
water solubility with delayed gel formation.
When used at levels of 0.5 - 1.0%, SeaSpen
PF readily hydrates with minimum agitation
to provide a weak thixotropic gel structure.
SeaSpen PF can be used in suspension,
reconstitutable suspension, topical, lotion,
and cream applications.
3
General Introduction
Carrageenan is a generic term applied to a
naturally occurring, commercially important
family of hydrophilic polysaccharides
extracted from a number of closely-related
species of red seaweeds. More specifically,
carrageenans are high molecular weight,
highly sulfated, linear molecules with a
galactose backbone. They are made up of
sulfated and nonsulfated repeating units of
galactose and 3,6-anhydrogalactose, which
are joined by alternating
(1 3) and
(1 4) glycosidic linkages.
History
Seaweed harvesting has been known for
5,000 years. Historically, seaweed has been
utilized in foods, medicines, and bookbind-
ing adhesives. Reference of carrageenan as
a food source dates back as far as 600 BC.
Carrageenan, however, became prominent
upon the discovery and harvesting of Irish
moss along the coast of Ireland in the
1300s. It was used to prepare jellies and
milk puddings. This led to the origin of
the French dessert, blanc mange. In the
early 19th century, its utility was expanded
to textiles and beer clarification. Production
of a refined extract was industrialized in
England in the early 20th century; however,
its trade was limited until World War II. With
the trade and production of agar impeded
by the war, carrageenan became widely
used as a replacement. As a result,
carrageenan gained a permanent market
position.
Carrageenan Source
Carrageenan is obtained from many different
species of red seaweed (Rhodophytes). The
most commercially important carrageenan-
bearing seaweeds are shown in Figure 1(1).
Carrageenan is the interstitial matrix between
the cellulosic fibers of the plant tissue
(Figure 2). The carrageenan comprises
2-7% of the weight of the wet sea plant
and 30-80% of dry plant weight.

Figure 1: Commercially Important Carrageenan Bearing Weeds(1)

Rhodophyceae
Class: (Red Algae)

Genus: Chondrus Iradaea Gigartoina Hypnea Eucheuma

Species: crispus cordata stellata cervicois spinosum

ocellatus boryana acicularis musciformis cottonii
undulosa pistillata edule
laminarioidos radula serra
chamissoi gelatinae
skottsbergii
canaliculata

Figure 2: Cross Section of Red Seaweed(2)

Cellulosic
Material Carrageenan
Fills Spaces
Between Cells

4
There are five major red seaweed producing
areas globally. Each area yields a different
distinct species of red seaweed (Table 1).
Carrageenan is a natural product, and the
amount of carrageenan yielded from a plant
will vary based on the species, growing con-
ditions and plant reproductive cycle. Kappa
and lambda carrageenans can typically be
obtained from the same seaweed species.
Each carrageenan type is obtained from an
independent plant of the same species that
grow together separately.

Table 1: Carregeenan Yield Data from Red Seaweeds

Red Seaweed Species Harvest Location Carrageenan Type Carrageenan Yielda
Chondrus Crispusb North Atlantic Kappa/Lambdac 33-36%
Eucheuma Cottoniib Philippines/Indonesia Kappa 25%
Eucheuma Spinosumb Philippines/Indonesia Iota 29%
Gigartina Radulab Chile Kappa/Lambdaa 40-48%
Gigartina Skottsbergii Chile Kappa/Lambdaa 50%
Gigartina Chamissoi Chile Kappa/Lambdaa 32%
Gigartina Canaliculata Mexico Kappa/Lambdaa 32%
Gigartina Acicularis Morocco Kappa/Lambdaa 35%
a
- Carrageenan yield is dependent on species, growing conditions, and reproductive cycle.
b
- Species of red seaweed from which FMC obtains commercial carrageenan.
c
- Lambda are obtained from independent plants which grow together separately.

Four species of red seaweed make up
the predominant amount of commercial
carrageenan used by FMC. Chondrus
Crispus (Figure 3), also known as Irish
moss, is a small bushy plant 4-10 cm in
height. It naturally grows and is harvested
in the shallow cold water harbors of the
North Atlantic Coast. The plants are raked
off rocks in a labor intensive harvest. Kappa
and lambda carrageenans are obtained
from haploid plant tissue and diploid
(spore-bearing) plants, respectively, which
grow together.

Figure 3: Chondrus Crispus

North
America
1 cm

Chondrus crispus

5
Gigartina Radula (Figure 4) grows worldwide The radula is the largest carrageenan
in cold coastal waters; however, it is mainly yielding plant. Both kappa (haploid plant)
harvested in Chile. It is a bushy or leafy plant and lambda (diploid plant) carrageenans
that can grow up to five meters in height. are obtained.

Figure 4: Gigartina Radula(2)

South
America

10 cm

Two important Eucheuma species of grows to approximately 50 cm in height.

carrageenan are obtained from the warm The Eucheuma spinosum is a spiny, bushy
waters of the South Pacific Ocean (Figure 5). plant approximately 50 cm in height, and it
The Eucheuma cottonii yields only kappa yields only iota carrageenan.
carrageenan. It is a smooth bushy plant that

Figure 5: Eucheuma Cottonii and Eucheuma Spinosum

10 cm
10 cm

Eucheuma cottonii Eucheuma spinosum

6
Processing
Carrageenan processing consists of many
important steps (Figure 6). Harvesting the
raw seaweed is the initial step. Once the
seaweed is harvested, it must quickly be
dried and baled. This is a critical step
because the quality of the final product
depends on quickness of drying. The
longer the seaweed remains wet, enzymatic
effects reduce the quality and, ultimately,
alter the functionality and properties of the
carrageenan extract. When the seaweed
arrives at the processing facility, the
carrageenan is extracted using a hot alkali
solution. The alkalinity and temperature
swells and macerates the seaweed allowing
the carrageenan to be extracted. By varying
the extraction time and conditions, a variety
of differentiated functional products can be
produced. Once extracted, the carrageenan
is clarified to eliminate extraneous solids.
The hot solution is then concentrated prior
to recovery.

Figure 6: Schematic of Carrageenan Processing(2)

Harvest

Hot Extraction

Clarification

Concentration by Evaporation

KCI KCI
Precipitation
Water Alcohol Water

Concentration

Freezing Alcohol Evaporation Press

Drying

Grinding

Blending

7
Carrageenan can be recovered by three
different methods. The methods include gel
recovery, freeze/thaw recovery, and alcohol
precipitation. Kappa carrageenan, due to its
syneresis ability, can be obtained using all
three methods, however, iota and lambda
carrageenan can only be recovered by
alcohol precipitation. The carrageenan is
recovered by coagulation with isopropyl
alcohol. Once the carrageenan has been
recovered, the extract is dried, ground
and blended to ensure product uniformity.
extracts through process controls specific
to customer needs. Such controls enable
functional properties such as viscosity,
gel strength, and molecular hydration to
be specifically altered. Viscosity can be
altered (Figure 7) by preserving the
molecular weight (MW) of carrageenan
molecule. This is achieved by shortening
or extending the processing time as well
as harshness of the alkali treatment.

Processing Effect on Carrageenan

Properties

With over forty years of experience,

FMC can prepare a variety of carrageenan

Figure 7: Carrageenan Viscosity as a Function of Processing

Process Time
Processing time and harshness of alkali maximization of the 3,6-AG units, gel
treatment (Figure 8) also controls gel strength will begin to decrease as a result
strength. A longer processing time of the continual reduction in the MW of
increases the number of 3,6-anhydrogalac- the molecule.
tose (3,6-AG) units and maximizes the
potential gel strength of the carrageenan
molecule. Each carrageenan molecule,
however, contains a finite number 3,6-AG
units. If processing continues after

8
Figure 8: Carrageenan Gel Strength as a Function of Processing
Gel Strength

Processing Time
Molecular hydration is a function of the
carrageenan recovery process (Figure 9).
Alcohol dehydration produces a fibrous,
stringy material with a large surface area,
and a low electrolyte content. These
attributes allow carrageenan molecules
to hydrate quickly and easily. The gel or
freeze/thaw recovery methods produce a
non-fibrous, tightly packed dense material
that has a higher electrolyte content.
These attributes do not allow the
molecules to hydrate quickly.

Figure 9: Hydration of Carrageenan as a Function of Processing

Alcohol Recovery
Hydration

Gel Recovery

Time

9
Molecular Structure
There are three commercially important
carrageenans that exist currently (Figure 10).
These structures consist of D-galactose
molecules joined together by alternating

-1,3 and -1,4 by glycosidic linkages.
They are differentiated from each other by
the amount of 3,6-AG they contain as well as
the number and position of ester sulfate
groups present.

Figure 10: Structures of Kappa, Iota and Lambda Carrageenan

Kappa ()

Iota ()

Main Differences:
1) Amount of 3,6-anhydrogalactose
2) Number and position of ester
sulfate groups
Lambda ()

Kappa and iota are gelling carrageenans. Understanding structural characteristics

Each carrageenan is composed of such as the amount of 3,6-AG and number
alternating 1,3-linked galactose and and position of sulfate groups is important
1,4-linked 3,6 AG residues. The difference because these attributes help define the
exists in the number and position of the properties each carrageenan exhibits.
ester sulfate groups. Kappa contains a The general contents of each characteristic
single substituted sulfate group in the 4 are displayed in Figure 11.
position on the galactose residue. In
addition to the substituted 4-sulfate group
on the galactose residue, iota also contains
a second sulfate group substituted in the
2 position of the 3,6-AG residue. Lambda
carrageenan is a non-gelling carrageenan.
It is composed of alternating 1,3 and 1,4-
linked galactose residues. Sulfate groups
are substituted in the 2 position of each
galactose residue as well as the 6 position
of the 1,4-linked residue.

10
Figure 11: Ester Sulfate and 3,6-Anhydrogalactose Contents of Kappa, Iota,
and Lambda Carrageenan
Kappa Iota Lambda
Carrageenan
Fraction

Ester Sulfate 18-25 25-34 30-40

(% w/w)

3,6-Anhydrogalactose
34 30 None
(% w/w)

The 3,6-AG content indicates the ability
of the carrageenan to form a gel. Without
the 3,6-AG unit, gelation will not occur.
This has been attributed to kinks in the
chains that tend to inhibit helix formation.
Theoretically, the precursors of kappa and
iota carrageenan contain no 3,6-anhydride
linkages, but rather a 6-sulfate group
substituted in the 1,4-linked galactoside(3).
This 6-sulfate group creates the kinks in
the polysaccharide backbone that inhibit
gelation. In nature, the seaweed will contain
varying amounts of 6-sulfation and 3,6-AG.
An enzyme named dekinkase(4) present in
the seaweed will cleave this 6-sulfate group
and induce ring closure to form the 3,6-
anhydride linkage. Hot alkali treatment
during extraction will induce cleavage and
ring enclosure as well (Figure 12). Upon for-
mation of the 3,6-AG unit, the kinks are
removed, and a more linear and smooth
molecule capable of helical formation is
produced.

Figure 12: Conversion of 6-Sulfate Group to the 3,6-Anhydrogalactose Group(5)

11
Ester sulfate content also effects the
properties of each carrageenan. Figure 13
indicates that as ester sulfate content
increases, there are decreases in syneresis
and gel strength, and increases in gel clarity,
Figure 13: Properties of Carrageenan as a Function of Ester Sulfate Content(5)
Properties
Carrageenans tend to be cream colored
powders. Depending on the recovery
method, they will be short fibrous segments
or thin flakes. Typically, 95% of the ground
powders pass through No 80 mesh. Finer
mesh products are available up to 325 mesh.
The average particle density is 1.7 g/cm3.
The bulk density for thin flakes is 1 g/cm3
and 0.6 g/cm3 for fibrous powders. The
carrageenan is polydispersed and the
molecular weight is normally between
100,000-500,000 Daltons.
12
freeze/thaw tolerance, and gel compliance.
This is attributed to the increased steric
hindrances that disrupt the formation of
an enhanced 3-dimensional network.
Solubility
Water - All carrageenans are soluble in hot
water (Table 2). Sodium salts of both kappa
and iota carrageenans are soluble in cold
water. Potassium and calcium salts do not
dissolve; however, they exhibit the ability to
swell. Swelling is variable and is dependent
upon the type and level of cations present
and the particle density. Iota carrageenan is
sensitive to calcium ions and it will swell to
form thixotropic dispersions. The thixotropy
results from the formation of divalent calcium
bridges between the swollen particles to
form a loose 3-Dimensional network.
Lambda carrageenan displays full solubility
in cold water. Solubility is independent of
the cations associated with it.

Table 2: Solubility Characteristics of Carrageenan

Kappa Iota Lambda

Solubility

80C Water yes yes yes

+ +
20C Water Na salt soluble Na salt soluble yes
+ ++ ++
K , Ca and Ca salt swells
+
NH4 salt swells to form thixotropic
dispersion

Hot swell swell soluble

Cold no no swell

Sugar and Salt Solutions - Kappa and indicated that solubility of iota carrageenan
lambda carrageenans are soluble in hot is sensitive to the associated cation
sucrose solutions up to 65%. Iota content(5).
carrageenan, however, is only sparingly
soluble under the same conditions. Under
high electrolyte conditions, iota and lambda
carrageenans will remain soluble. Kappa,
however, does not display such tolerance
and will be salted out.

Water Miscible Solvents - All carrageenans

are compatible with water miscible solvents
such as alcohol, propylene glycol, and
glycerin. The percentage of the solvent
tolerated is dependent upon the carrageenan
type, MW of the carrageenan, cation
concentration, and the method of solvent
incorporation. The more hydrophilic the
carrageenan molecule, the greater the
solvent tolerance will be. Solubility
characteristics of carrageenans in dry
polyols and polyol mixtures are shown
in Tables 3 and 4, respectively. The data

13
Table 3: Solubility of Kappa and Iota Carrageenan in Dry PolyolA
Carrageenan Polyol Solubility in Anhydrous Polyol
Kappa Ethylene Glycol Insoluble up to 95C
Kappa Glycerin Insoluble up to 95C
Kappa Propylene Glycol Insoluble up to 95C
Iota Methanol Soluble, will not coagulate
Iota Ethylene Glycol Soluble Hot
Iota Glycerin Soluble Hot
Iota Propylene Glycol Insoluble up to 95C
Iota 1,3-Propanediol Insoluble up to 95C
A
- Obtained from Reference 5.

Table 4: Solubility of Carrageenan in Water/Polyol MixturesA,B

Carrageenan Polyol Water/Polyol Ratio
Kappa Glycerin 40/60
Na+/Ca+2 Iota Glycerin 30/70
Na+/K+ Iota Glycerin 0/100
Na+/Ca+2 Iota PEG - 600 40/60
Na+/K+ Iota PEG - 600 20/80
Na+/Ca+2 Iota Ethylene Glycol 10/90
Na+/K+ Iota Ethylene Glycol 0/100
A
- Obtained from Reference 6.
B
- Up to 2% Carrageenan.

Organic Solvents - Kappa, iota, and lambda
carrageenans are generally insoluble in
organic solvents.
Gelation
thermoreversible gels. The gels will become
fluid when heated above their melting
temperature and will reset upon cooling
with minimal to no loss of their original gel
strength (Figure 15).

Kappa and Iota are gelling carrageenans.

In order for gelation to occur, the helix of
a single carrageenan molecule must come
in close proximity to a second identical
single carrageenan helix to form a double
helix. The double helices then must
aggregate to form a 3-dimensional network.
A general mechanism of gelation is shown
in Figure 14. The mechanism indicates
that both kappa and iota gels are

14
Figure 14: General Gelation Mechanism of Carrageenan(5)

Solution Gel I Gel II

Figure 15: Thermoreversibility of Carrageenan Gels(2)

15
Kappa carrageenan (Table 5) forms its
strongest gels with potassium ions. The
gels tend to be strong and brittle. Figure 16
illustrates a gelation mechanism for kappa
carrageenan based on traditional theory(6).
It is believed that potassium ions neutralize
the sulfate group on the kappa molecule.
This allows two carrageenan molecules to
move close enough for hydrogen bonding to
occur and form a double helix. The resultant
helices begin to hydrogen bond and
aggregate. The aggregated helices form
crystalline like regions that refract light
and produce a slightly opaque gel. These
aggregated helices provide the strength
and brittleness to the gel; therefore, when
sheared, brittle fracture occurs and the
gel is unable to reheal itself. Over time, the
aggregated helices form stronger associa-
tions resulting in the contraction of the gel.
As the gel contracts, the water is destabi-
lized and squeezed out of the gel. This
phenomenon is known as syneresis. The
syneresis process is dramatically increased
upon freezing the gel. The water in the gel
expands as it freezes and helps create
stronger associations as the helices are
forced closer together. Upon thawing,
the water remains destabilized resulting
in gel instability.

Table 5: Gelation Properties of Carrageenans

Kappa Iota Lambda

Gelation
Heat to 80C/
Cool to 25 C
+ ++
Strongest Gels with K ion with Ca ion no gel

Regelation no yes no
after Shear

Syneresis yes no no

Freeze/Thaw no yes yes

Stability

Synergism with yes no no

Other Gums

16
Figure 16: Proposed Gelation Mechanism of Kappa Carrageenan

Distance closes
to < 3:
H-bonding occurs

Distance closes
to < 3:
H-bonding occurs

Iota forms its strongest gels with calcium removal as the divalent calcium bridges
ions (Table 5). The gels tend to be weak reform to produce a gel.
and elastic. The gelation mechanism
(Figure 17) is believed to be similar to the
kappa mechanism. Neutralization of the
4-sulfate groups allows the iota molecules
to hydrogen bond and form double helices.
The additional sulfate group is believed to
create a steric hindrance that prevents the
hydrogen bonding and helical aggregation.
Divalent calcium bridges create a more
flexible loose 3-dimensional network.
This results in a weaker gel with an elastic
texture. The absence of aggregates of
double helices eliminates any crystalline
like regions and results in a clear gel. The
loose 3-dimensional network that controls
water mobility in flexible pockets reduces
syneresis. When exposed to a freeze/thaw
cycle, the water remains stabilized and
associated with the network. When sheared,
the calcium bridges are disrupted and flow
begins. Thixotropy occurs upon shear

17
Figure 17: Proposed Gelation Mechanism of Iota Carrageenan

Distance greater
than 3:

Repulsion of sulfate
group prevents
helical aggregation.

Lambda is a non-gelling carrageenan. The

absence of the 3,6-AG groups produces a
randomly coiled molecule with an irregular,
kinked structure. The structure sterically
prevents double helical formation and
gelation from occurring.

Gel Texture Modification

By blending carrageenans together, one can

modify the gel texture of carrageenan gels.
Figure 18 indicates that a variety of textures
and properties of kappa and iota gels can
be obtained. Texture alteration can also be
achieved by combining lambda carrageenan
with kappa and iota carrageenan as well.
Gels with a variety of textures and
characteristics are obtained.

18
Figure 18: Modification of Gel Texture of Kappa and Iota Carrageenan Gels(2)
Effect of Cations
Carrageenan powders will always have
cations associated with it. The amount and
type of cations associated will vary with
processing. The cations predominantly
associated with carrageenan are sodium,
potassium, calcium, and magnesium.
The presence of these cations is critical
because they help to define the properties
exhibited by carrageenan powder being
used. For example, potassium and calcium
produce the strongest kappa and iota gels,
respectively; however, kappa and iota
will not form significant gels with sodium
ions.
By controlling cations, it is possible to
obtain specific desired properties. There
are several ways to control and manipulate
cations. First, specific amounts of water
soluble salts (i.e. KCL, CaCL2) can be
supplied to any system to obtain the desired
outcome. Secondly, the carrageenans can
19
be ion exchanged to produce the desired
properties. If ion exchange is not possible,
then the addition of sequestering agents
(i.e. EDTA, sodium hexametaphosphate) can
remove cations from the system in process.
The presence of cations will effect the
ease of dispersion, dissolution temperature,
gelling temperature, melting temperature,
and gel strength. Increasing the cation
concentration of the dispersion media
increases the ease of dispersion. The
water of hydration preferentially interacts
with the cations; therefore, the hydration
of carrageenan is hindered. This results
in the carrageenan dispersing more as
individual molecules instead of aggregating
into clumps.
The dissolution temperature of carrageenan
increases with cation concentration
(Figure 19). The increased salt levels hinder
solubility because there is less free water
available in the system to interact with the
carrageenan. Therefore, higher temperatures the solvated cations to dissolve the
are required to free enough water from carrageenan.

Figure 19: Effect of Cations on Carrageenan Dissolution

Gelling and melting temperatures also

increase with cation concentration
(Figures 20 and 21). As cation levels
increase, the carrageenan molecules are
neutralized more quickly and extensively.
This results in the formation of additional
double helices that begin to create a more
extensive 3-dimensional network at higher
temperatures. Melting temperatures are
generally higher than the gelling tempera-
tures. This hysteresis is attributed to the
extra energy required to overcome the
helical associations to melt the network.
The hysteresis is 10-15C and no more than
5C for kappa and iota gels, respectively.

20
Figure 20: Effect of Gelling Cations on the Gelation Temperature of Carrageenan Gels(2)
Additional Cation Increases
Gelling Temperature

Figure 21: Effect of Potassium Ions on the Melting and Gelation Temperature
of Kappa Carrageenan Gels(1)

21
The gel strength of kappa and iota gels Increased cation levels result in enhanced
increases with potassium and calcium ion associations that create a stronger more
concentrations, respectively (Figure 22). extensive 3-dimensional network.

Figure 22: Effect of Cations on the Gel Strength of Kappa Carrageenan(5)

Cation Effect on Gel Strength

Synergism with Other Gums

Kappa carrageenan is synergistic with locust
bean gum (Figure 23) and konjac mannan
(Figure 24). These synergistic interactions
enhance the gel strength and water binding
capabilities, as well as modify the gel texture
to be more elastic and resilient.

22
Figure 23: Synergistic Effect of Locust Bean Gum and Kappa Carrageenan(5)

Figure 24: Synergism of Kappa Carrageenan and Konjac Mannan(2)

Stress in Grams

Penetration in cm

23
Effect of pH
All carrageenans are generally most stable
at neutral and alkaline pHs. In the solution
state, however, all carrageenans will be
subject to hydrolysis under acidic pH
conditions. Hydrolysis may result in a loss
of viscosity and gelling potential. The rate
of hydrolysis is a function of pH, tempera-
ture, and time (Figure 25). In addition,
resultant kappa and iota gels are stable at
low pH (pH 3.0). This is attributed to the
formation of double helices, which are more
resistant to hydrolysis. Lambda solutions
are relatively more acid stable than kappa
or iota solutions.

Figure 25: Effect of pH on Kappa Carrageenan

Rheology
Above their gel temperature, kappa and iota
carrageenans display psuedoplastic behavior
(Figure 26). As gelation occurs, viscosity
increases dramatically. Kappa gels cannot
be sheared to form a flowable liquid;
however, iota gels will display thixotropic
behavior when sheared (Figure 27). Lambda
carrageenan will display psuedoplastic
behavior under all conditions.

24
Figure 26: Rheology of Carrageenan in the Gel State(5)

Figure 27: Thixotropic Behavior of Iota Carrageenan(2)

25
Viscosity of carrageenan solutions will vary
according to concentration, temperature,
ion strength, and molecular weight. First,
viscosity increases with carrageenan
concentration (Figure 28) and molecular
weight (Figure 29). This is due to the extent
of molecular entanglements created by
the carrageenan molecules. Additional
carrageenan molecules create more
extensive entanglements. As molecular
weight molecules increase, more extensive
entanglements occur that are more difficult
to untangle; therefore, viscosity is increased.
Figure 28: Lambda Carrageenan Viscosity as a Function
of Concentration and Temperature(5)
26
Next, viscosity will decrease with increasing
temperature (Figure 28). Higher temperatures
decrease the hydration extent of the
carrageenan molecules. This allows the
molecules to slip by each other more easily
and results in viscosity reduction. As the
ionic strength increases, solution viscosity
will decrease. Increased ion concentrations
preferentially strip the water of hydration
from the carrageenan; therefore, the
carrageenan folds upon itself creating
a smaller flow unit (Figure 30).
Figure 29: Carrageenan Viscosity as a Function of Molecular Weight(5)

Figure 30: Carrageenan Viscosity as a Function of Ion Strength

ion

ion ion
ion

ion

ion

27
Protein Reactivity
All carrageenans are known to be protein
reactive. Reactivity is a function of the
isoelectric point (pI) of protein, the pH of
system, the weight ratio of protein to
carrageenan, the type of protein, and the
molecular weight. The interaction between
proteins and carrageenan occur by a
combination of two mechanisms. The
mechanisms are divalent bridging and ionic
bonding. Above the pI of the protein, the
carboxylic acid groups of the protein will
be ionized; therefore, the carrageenan does
not interact with the protein due to negative-
Figure 31: Protein Reactivity with Carrageenan Above the Protein Isoelectric Point
by Divalent Bridging(5)
Interaction Mediated by Divalent Cation
28
negative repulsions (Figure 31). Interaction,
however, may occur in the presence of
divalent cations such as calcium. The calci-
um will form a divalent bridge between the
protein and carrageenan molecule. This type
of carrageenan protein interaction generally
results in a soluble complex. Below the pI
of the protein, the amino groups of the
protein will be ionized (Figure 32). A direct
ionic interaction will occur between the
positively charged amino groups of the
protein and the negatively charged sulfate
groups of the carrageenan. This interaction
typically results in the precipitation.
Figure 32: Protein Reactivity with Carrageenan at and Below
the Protein Isoetectric Point(5)
At Isoelectric Point

Protein
Partial Interaction;
No Precipitation

Carrageenan

Below Isoelectric Point

Protein

Complete Interaction;
Precipitation Possible
Carrageenan

Dispersion of Carrageenan Order of addition is also critical.

Being able to properly disperse carrageenan
is essential to deriving its optimal functionali-
ty. Carrageenan can be dispersed several
different ways. First, dry carrageenan
powder can be slowly sprinkled into the
vortex of mixing water. Clumping of the
powder may occur. Applying gentle heat
will enable the clumps to wet and dissolve.
Secondly, a dispersion aid such as sucrose
or dextrose can be used. The dispersion aid
helps to separate the carrageenan molecules
and prevent clumping from occurring. Finally,
the carrageenan can be slurried with glycerin
or propylene glycol. The carrageenan has
limited solubility in the polyols and prevents
clumping from occurring upon mixing with
water.
Carrageenan should be dispersed and
completely functionalized prior to the
addition of other formula ingredients. The
only exception to this general rule is the
solubilization of parabens. If parabens are
added after the dispersion of carrageenan,
there will not be enough free water available
in the system to solubilize them, therefore,
inadequate preservation will result. The
addition of acids should be the last step
of ingredient addition. This will maintain
maximum carrageenan functionality by
limiting the exposure time of the carrageenan
molecules to acid while in the solution state.

29
Applications
Soft Chewable Delivery System
Kappa and iota carrageenans produce stable
gels at room temperature. These gels are
thermoreversible and can be cast or molded
into different shapes with a variety of
textures(7). These properties have enabled
the preparation of a soft chewable dosage
form for the delivery of pharmaceutical,
nutritional, and veterinary agents with
superior textural properties and mouthfeel.
This chewable system offers a smooth easy
bite, a creamy mouthfeel, easy breakage
into small slippery discrete pieces, no
sticking to the teeth or tooth-packing, and
textures which can be altered. Samples
containing actives such as calcium
carbonate, aluminum and magnesium
hydroxide, and acetaminophen have
been prepared.
Suspensions
Carrageenan forms stable 3-dimensional
networks that are capable of suspending
pharmaceutical ingredients and dense color
Figure 33: Reconstitutable Suspension Preparation Using Dry Blends
Containing Carrageenan
H2O
Add Water
H2O
Dry Powder Wet
Dry Powder
3-10 Seconds
30
pigments for extended periods of time
without remixing or shaking(8). Iota
carrageenan suspends by thixotropy. The
thixotropic 3-dimensional iota network has
a high yield point, and creates a barrier
that entraps the suspended particles and
prevents separation. Once shaken or
sheared, the thixotropic network is broken
and becomes flowable. Iota carrageenan at
0.50-0.75% use levels are recommended.
Reconstitutable Suspensions
Reconstitutable suspensions can be
prepared using iota carrageenan(9). This
can be achieved by dry blending iota
carrageenan (0.50-0.75%) with a dispersing
aid, active, and other desired ingredients.
The powder will reconstitute upon the addi-
tion of water and shaking vigorously by hand
for one minute (Figure 33). During shaking,
the iota carrageenan hydrates and dissolves
to form a stable thixotropic suspension. For
longer shelf life applications, the suspension
becomes pourable upon hand shaking, and
will remain stable in excess of two weeks.
Shake
1 Minute
1 Minute
Controlled Release
Carrageenans (kappa, iota, and lambda)
have been investigated for use in controlled
release tablets(10-13). The carrageenans
are incorporated as dry powder excipients
to the tablet formulation and compressed.
Literature reports indicate that release rate
can be altered or controlled by using
carrageenan use levels from 10-100%(10-13).
As the compressed tablet comes in contact
with the dissolution media, the carrageenan
on the surface will hydrate and create a
thin gel layer around the remaining dry
tablet (Figure 34). The gel layer restricts
water mobility and slows penetration into
the tablet matrix. This results in reduced
active solubilization as well as diffusion of
the active ingredient from the matrix. Near
linear release profiles from tablets containing
carrageenan have been reported(10-13).
Hariharan et al(11) employed multiple regres-
sion analysis to predict the time in minutes
required for 50% of the drug to be released
(t50) from the tablet. A contour plot of the
response(t50) predicted by the equation
(model) is shown in Figure 35. The fitted
model demonstrated that slow releasing
formulations can be obtained over a certain
range of mixtures of alpha- and lambda-
carrageenan and Avicel microcrystalline
cellulose.

Figure 34: Controlled Release of Active Ingredients from Tablet Matrices

Containing Carrageenan

Controlled Release Tablets

Figure 35: Controlled Release Tablets Contour Plot of Predicted t50%

with Respect to Experimental Formula(11)
Avicel = 1
Gelcarin = 0
Viscarin = 0

Viscarin = 1 Gelcarin = 1
Gelcarin = 0 Viscarin = 0
Avicel = 0 Avicel = 0

31
Encapsulation and Entrapment
Iota and kappa carrageenans have been
used for the entrapment and encapsulation
of oils, flavors, fragrances, and irregular
particles(14). The textures and size of the
resultant beads can be varied. Encapsulation
can be accomplished by combining an oil
with an emulsifying agent and pumping into
a carrageenan solution to enrobe the droplet
with carrageenan. The enrobed oil droplet
is then dropped into a potassium chloride
solution to induce the carrageenan to gel
around the oil droplet. To entrap, all active
ingredients are mixed in a liquid carrageenan
solution. Next, droplets of the mixture are
allowed to drip into a potassium chloride
solution to induce the gelation of the
carrageenan.
Emulsion Stabilization
Emulsions have been stabilized using iota
and lambda carrageenan(15,16). Carrageenan
itself is not an emulsifier; however, it works
most effectively in combination with small
amounts of an emulsifying agent. The
carrageenan provides viscosity and
3-dimensional structure to the aqueous
phase of the emulsion. These attributes
create a suspension of oil droplets and
limit the mobility of the oil droplets to
prevent coalescence.
32
Other Applications
Carrageenans have been utilized in a variety
of other applications. First, carrageenans
can be used in chewable tablet applications.
Upon chewing, the carrageenans hydrate
and provide a slick creamy mouthfeel.
Combinations of kappa, iota, and lambda
carrageenan have been used in suppository
and topical gel bases(17,18). Matrices with
suitable integrity for suppository usage can
be prepared. Release profiles were found to
be a function of carrageenan content and
displayed linear square root of time release.
Topical gel bases were also dependent of
carrageenan content, and displayed diffusion
kinetics. Next, liquid eye drops containing
carrageenan have been prepared(19). The
drops were designed to gel upon contact
with the ions contained in lachrymal fluid.
The thin gel is maintained in the eye
producing increased residence times
and more effective delivery of therapeutic
agents. Vaginal formulations containing
carrageenan have also been formulated(20-22).
Carrageenan has been reported to be
effective against the infection of sexually
transmitted pathogens in concentrations
as low as 0.05%. Finally, carrageenans
prevent crystal growth. The 3-dimensional
carrageenan network physically disrupts
the formation of crystal lattices.
 Marine Colloids Carrageenan, N.F.
Pharmaceutical Product Summary
Product Name CGN Type Viscosity Gel Type Water Solubility Use Level Applications
Gelcarin GP 379 Iota High Elastic Hot 0.3 - 1.0% Creams; Supsensions
Thixotropic Medium Strength Polyol Reactive
Protein Reactive
Promotes Freeze/Thaw
Gelcarin GP 911 Kappa Low Brittle Hot 0.3 - 1.0% Encapsulation/Delivery
Firm Systems
Polyol Reactive
Protein Reactive
Gelcarin GP 812 Kappa Low Brittle Hot, Partial Cold 0.25 - 2.0% Stronger Gels that GP 911
Firm Note: syneresis higher than
GP 911
Viscarin GP 109 Lambda Medium Non-Gelling Partial - Cold 0.1 - 1.0% Creams, Lotions
Full - Hot Polyol Reactive
Protein Reactive
Viscarin GP 209 Lambda High Non-Gelling Partial - Cold 0.1 - 1.0% Creams, Lotions
Full - Hot Polyol Reactive
Protein Reactive
Viscarin GP 328 Multi Medium-High Weak Hot 0.7 - 1.2% Creams, Lotions
Kappa/Lambda Excellent for Maintaining
Emulsions
SeaSpen PF Iota Medium Elastic Cold 0.5 - 1.0% Suspensions
Thixotropic Weak Delayed Gel Topical Lotions/Creams
Formulation Reconstitutable Suspensions

33
References
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2. Thomas, W.R., in Thickening and Gelling
Agents for Food, A. Imeson, Ed., Blackie
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1992, pp. 25-39.
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Pharm. Res., 14: S41 (1997) abstract
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Lang, JC (to Alcon Laboratories), US
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2000 FMC Corporation. All rights reserved. RS