International Journal of ChemTech Research
CODEN( USA): IJCRGG
ISSN : 0974-4290
Vol.2, No.1, pp 509-525,
Jan-Mar 2010

NATURAL POLYSACCHARIDE HYDROGELS AS NOVEL
EXCIPIENTS FOR MODIFIED DRUG DELIVERY SYSTEMS: A REVIEW*K.M.Manjanna, 1T.M. Pramod Kumar,2B. Shivakumar*Department of Pharmaceutics, T.V.M.College of Pharmacy, Bellary Karnataka, India
1

Department of Pharmaceutics, J.S.S. College of Pharmacy, Mysore, Karnataka, India.

2

Department of Pharmaceutical Chemistry, S.C.S.College of Pharmacy, Harapanahalli,
Karnataka, India.
*Corres.author:kmhuruli@rediffmail.com
Phone no- 919449409683

ABSTRACT: Drugs are rarely administered as pure chemical substances alone and are almost always given as formulated
preparations or medicines. Drug dosage forms contain many components in addition to the active pharmaceuticalingredient(s) to assist in the manufacturing process as well as to optimize drug delivery. Due to advances in drug delivery
technology, excipients are currently included in novel dosage forms to fulfill specific functions and in some cases they
directly or indirectly influence the extent and/or rate of drug release. Developments of several drug delivery systems are
based on natural polysaccharides act as excipients that do not change their chemical structure but these materials degrade
within the body as a result of natural biological processes, eliminating the need to remove a drug delivery system after
release of the active agent has been completed. Furthermore, polysaccharides are chemically well-defined and have attracted
worldwide attention as excipients due to their novel and unique physico-chemical properties can be relatively low cost andcan be chemically modified to suit specific needs. Some natural polysaccharides have even shown environmental-responsive
gelation characteristics with the potential to control drug release according to specific therapeutic needs. This review
discusses some of the most important natural polymeric compounds that are used or investigated as excipients in drugdelivery systems.
Keywords: Natural polysaccharides; polymers; excipients; drug delivery; Modified release; Drug release modifiers.

INTRODUCTION
Pharmaceutical excipients are substances other than the
API which have been appropriately evaluated for safety
and are intentionally included in a drug delivery system.
Traditionally, excipients were included in drug
formulations as inert vehicles that provided thenecessary weight, consistency and volume for the correct
administration of the active ingredient, and performanceof technological functions that ensure ease of
manufacture. The specific application of naturalpolysacccharide polymers in pharmaceuticalformulations include to aid in the processing of the drugdelivery system during its manufacture, protect, support
or enhance stability, bioavailability or patient
acceptability, assist in product identification, or enhance
any other attribute of the overall safety, effectiveness ordelivery of the drug during storage or use.1 The design ofeffective drug delivery systems has recently become an
integral part of the development of new medicines. The
goal is to provide a therapeutic quantity of medicine(s)to the proper site in the body in order to achieve thedesired effect and maintain such effect for the entire

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)period of treatment. Hence, research continuously keeps
on searching for ways to deliver drugs over an extended
period of time, with a well-controlled release profile.
Developments of several drug delivery systems are
based on natural polymers that do not change theirchemical structure but these materials degrade within the
body as a result of natural biological processes,
eliminating the need to remove a drug delivery systemafter release of the active agent has been completed.
Moreover these modify, drug release to achieve thedosage forms to release the drug in a constant mannerand maintain steady state plasma concentration for theentire period of treatment to reduce the dose related
adverse effects. The recent
rediscoveryofpolysaccharide based materials is also attributable to
new synthetic routes for their chemical modification,with the aim of promoting new biological activities
and/or to modify the final properties of the biomaterials
for specific purposes. 2
Polymers have been successfully employed in theformulation of solid, liquid and semi-solid dosage forms
and are specifically useful in the design of modified
release drug delivery systems. Both synthetic and naturalpolymers have been investigated extensively for thispurpose 3 but the use of natural polymers forpharmaceutical applications is attractive because they
are economical, readily available, non-toxic, and capableof chemical modifications, potentially biodegradable andwith few exceptions, also biocompatible. Because of
their wide diversity in structure and physical properties
natural polysaccharides have found a wide range ofapplications in the food, pharmaceutical and otherindustries.4 Some of these applications include their use
as emulsi-fiers, stabilizers, binders, gelling agents,
coagulants, lubricants, film formers, thickening andsuspending agents. These biopolymers are rapidly
emerging as a new and industrially important source ofpolymeric materials which are gradually becoming
economically competitive with natural gums produced
from marine algae and other plants.
Drug delivery
The aim of our drug delivery research is to optimize thebioavailability of drug compounds by innovative
formulation development. Our overall hypothesis is that
intrinsic drug delivery of drug candidates may be
manipulated by chemical and/or excipient formulation
strategies aiming to:· increase drug candidate solubility in biofluids such asintestinal fluid· increase drug stability in the formulation and inbiofluids· increase
drug candidate permeability acrossbiomembranes, such as the small intestinal membrane510· increase

drug
candidatedeliverytothepharmacological target· Decrease drug candidate metabolism, and/or decrease
its elimination.
Solubility in biofluids may be influenced by salt or
prodrug formation, for example, or by the formation of
excipient-drug-candidate complexes. Stability can be
optimized by using excipients such as detergents, or byfreeze-drying the formulation for long-term storage. It is
possible to increase permeability across biomembranes
by designing drug candidates as drugs or prodrugs thatare substrates for absorptive membrane transporters, orby developing lipid or particulate drug-excipient systems
such as emulsions, liposomes and nano particles that
influence permeability.
Increased delivery
topharmacological targets can also be influenced by pH or
enzyme sensitive controlled release formulations basedon either chemical or excipient formulation strategies.
First pass metabolism in the liver and elimination of
drug candidates can be influenced by designing them as
non-substrates for metabolizing enzymes, or as
substrates for reuptake transporters, or by applying
excipients that are regulators for efflux transporters or
metabolizing enzymes, or by using alternative
administration routes 5
Pharmaceutical technology
There is a complex interplay between the physical andchemical properties and related unit operations of theactive pharmaceutical ingredients as well as theexcipients. This research area addresses the issue andfocuses on the molecular-based formulation of solidstate pharmaceutics. The main target is to widen anddeepen our understanding of material properties during
the manufacture of pharmaceutics, with special focus on
the processability of solid-state forms in relation to thebioavailability of these forms. This research area will
pay special attention to the identification of themechanisms of solid-state transitions by real time
analysis of the complex phenomena occurring in processenvironment. Understanding material properties inrelation to the processability of pharmaceutics opens
new perspectives for improved quality and more
efficient production.6
Optimal drug therapy
Medicines are the dominating treatment technology inhealth care and in the population’s self care, andconsumption is still increasing. Besides the beneficial
effects, the use of medicines is also related to a wide
variety of problems, which include interactions, adverse
effects, misuse and non-compliance. In addition, drug
costs may be a burden to the individual and to society.
The overall aim of this central research area is toK.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)optimize the prescribing and use of medicines byminimizing drug-related problems and costs. The
research area deals with analyses of: determinants ofmedicine use and associated health and economic
outcomes; the behaviours and perceptions of medicines
by professionals and consumers; the efficacy and safetyof medicine use in the clinic and in the population;
processes of knowledge creation in drug development
and use; professional practice. Interventions aiming to
optimise drug use and therapy are also conducted andevaluated. Research integrates scientific skills from amultiplicity of disciplines including epidemiology,
health economy, clinical pharmacy and social
pharmacy.7
Polymers in drug delivery
One of the most remarkable and useful features of apolymer's swelling ability manifests itself when thatswelling can be triggered by a change in the environment
surrounding the delivery system. Depending upon thepolymer, the environmental change can involve pH,
temperature or ionic strength and the system can either
shrink or swell upon a change in any of theseenvironmental factors of these sensitive systems. Drugrelease is accomplished only when the polymer swells
and because many of the potentially most useful pHsensitive polymers swell at high pH values and collapse
at low pH values, triggered drug delivery occurs upon an
increase in the pH of the environment. Such materials
are ideal for systems such as oral delivery, in which thedrug is not released at low pH values in the stomach, butrather at high pH values in the upper small intestine 8
Need for excipients in drug delivery

Pharmaceutical excipients are substances other thanthe API which have been appropriately evaluatedfor safety and are intentionally included in a drugdelivery system. For example, excipients can: aid
in the processing of the drug delivery system during
its manufacture, protect, support or enhancestability, bioavailability or patient acceptability,
assist in product identification, or enhance any otherattribute of the overall safety, effectiveness ordelivery of the drug during storage or use. To meet
emerging challenges, the pharmaceutical industry iscurrently in the midst of reinventing itself. These
challenges include continually increasing drug
development costs, slowing new product approval,
blockbuster drug patent expirations, price pressure andglobalcompetition.
Concurrently,
significant

511

opportunities exist for the pharmaceutical industry,including an increasing patient population, numerous
unmet medical needs, growing disease awareness,
globalization of operations and markets, and advances in
efficiency.
The focus on drug development costs is driving theindustry to consider outsourcing, relocating production
and sourcing ingredients from lower-cost locations.
These options are continually being explored to meet thechallenge of utilizing a more robust, streamlined andefficient manufacturing process, and to secure a supply
chain. To overcome the challenges of price pressure due
to "generitization" of branded drugs, as well as severe
global competition, even in the generic sector, many
pharmaceutical companies are seeking new proprietary
drug delivery formulations. Innovative, new excipients
offered by various excipient suppliers enable thedevelopment of new dosage forms, improve efficiency
and may reduce the cost of drugs. Excipients can addfunctionality to pharmaceutical products. They offer
opportunities to introduce new dosage forms, and thus
facilitate
theextensionofpatentlife.9GELLAN GUM
Deacylated Gellan gum (Gellan) is an anionic microbial
polysaccharide, secreted from Sphingomonas elodea,
consisting of repeating tetrasaccharide units of glucose,
glucuronic acid and rhamnose residues in a 2:1:1 ratio:[→3)––D–glucose–(1→4)––D–glucuronic acid–(1→4)––D– glucose–(1→4)– –L–rhamnose–(1→]. In thenative polymer two acyl substituents, L-glyceryl at O(2)and acetyl at O(6), are present on the 3-linked glucose.
On average, there is one glyceryl per repeating unit andone acetyl for every two repeating units. Deacylated
Gellan gum is obtained by alkali treatment of the native
polysaccharide. Both native and deacylated Gellan gum
are capable of physical gelation 10 To induce Gellangelation it is necessary to warm up preliminarily aconcentrated water solution of the polysaccharide: when
the temperature is decreased, the chains undergo aconformational transition from random coils to double
helices (Coil-Helix Transition). Then a rearrangement of
the double helices occurs leading to the formation ofordered junction zones (Sol-Gel Transition) 11 thus
giving a thermo-reversible hydrogel 12 Much stronger
physical thermo-reversible hydrogels are also obtainedby addition of mono and divalent ions to Gellansolutions or in acidic conditions. 13 The physical gelation
properties make this polysaccharide suitable as astructuring and gelling agent

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)512

Figure;1 Chemical structure of Gellan gum

PHYSICOCHEMICAL PROPERTIES
Gelling Properties of Gellan Gum.
Gelation of gellan solutions occurs abruptly uponheating and cooling of gellan gum solutions in thepresence of cations. Such sol-gel transitions are
considered as phase transition. The gelation of gellan
gum is a function of polymer concentration, temperature,and presence of monovalent and divalent cations insolution. At low temperature gellan forms an orderedhelix of double strands, while at high temperature asingle-stranded
polysaccharide
occurs,which
significantly reduces the viscosity of the solution. The
transition temperature is approximately 350C, but can
range from 30-500C. Below transition temperature, a
stiff structure is obtained (setting point), and results ingel formation. The mechanism of gelation involves theformation of double helical junction zones followed byaggregation of the double helical segments to form athree-dimensional network by complexation with cations
and hydrogen bonding with water.14 Addition ofmonovalent or divalent cations during cooling markedly
increases the number of slat bridges at junction zone,
thereby improving the gelling potential of gellan gum.
Various studies have been carried out to study the effectof different factors on the gel strength. Some of theimportant factors affecting gel strength are discussed
bellow.
Acetyl content
Acetyl content is the most important factor affecting the
gel strength. Gellan gum with different acetyl content
gives gels with different properties. Native gellan gum
provides soft, elastic, thermoreversible gels, and is very
weak because of bulky acetyl and glyceryl groups thatprevent close association between gellan polymer chainsin bulk-helix formation, and hinder compact packing of
the cross-linked double helix. Deacetylated gellan gum
forms firm, brittle and thermoreversible gel because of
the absence of acetyl and glyceryl groups.15

Type and concentration of ions
Ions have an impact on gel strength and brittleness.
Gellan does not form gel in deionised water, but theaddition of salts of calcium, potassium, sodium, andmagnesium causes an increase in these two properties.
Notably, divalent cations are more effective in achieving
this; even in gellan gels of very low concentration(0.2%, by mass per volume), a high strength wasachieved with a maximum at about 0.004% (by mass pervolume) calcium and 0.005% (by mass per volume)
magnesium. Similar gel strength can be achieved with
0.16% sodium or 0.12% potassium (by mass pervolume). Gellan high salts concentration (1%, by mass
per volume). A concentration of 0.1-0.2% gellan issuitable for many food systems. It is importanteconomically that strong gels can be obtained at low
concentration of gellan, with the incorporation of trace
amount of salt 16
Gel pH
Sanderson and Clark showed the gel strength to beenhanced within pH range of 3.5 to 8, whichcorresponds to the natural pH range of most foods.
Change in pH does not alter the setting point of the gel,but affects melting temperature in some cases. For
example, gels prepared with very low levels ofmonovalent ions melt at around 700C at neutral pH, but
at pH=3.5 the melting temperature is slightly increased.
This trend is not seen for divalent ions. 17
Presence of hydrophilic ingredients
Addition of hydrophilic ingredients like sucrose (atabout 10%, by mass per volume) tends to decrease theion concentration required for optimal gellan gel
strength.
Kasapis et al used transmission electron
microscopy to examine the changing nature of apolysaccharide network with increasing levels of sugar.
Mixtures of deacylated gellan (<1%) with low (0-20%)and high (80-85%) levels of sugar were prepared andstudied. Micrographs of the high sugar / gellan gels

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)produced clear evidence of reduced crosslinking in thepolysaccharide network, which exhibits a transition fromrubber to glass-like consistency upon cooling. 18
Tang et al. studied the effects of fructose and sucrose on
the gelling temperature, clarity, and texture properties ofgellan gels cross-linked with calcium or sodium ions.
They reported the gelling temperatures of gellansolutions to generally increase on the addition of
sucrose, whereas addition of fructose up to 35% (bymass per volume) had no effect. Incorporation offructose and sucrose markedly increased the gel clarity.
Effect of sucrose on gel strength was found to be
dependent on cation concentration. At low cation
concentrations, sucrose strengthened the gels; but at highcation concentrations, sucrose weakened them. 19
Temperature stability and flexibility of the melting
point
Gellan gum is stable at higher temperatures andmaintains its strength at 900C, whereas xanthan gum
looses 74% of its original strength after heating up to
900C. According to Sanderson and Clark, the melting
temperature can be below or above 1000C, depending on
the conditions of gel formation. The most importantfactor responsible for the flexibility of the melting point
is concentration of cations in the gels becausemonovalent and divalent cations markedly increase thenumber of junction zones in gels and make them moreresistant to temperature. Modification of the melting
point can successfully replace other conventional
thickeners / stabilizers, while used in much lower
concentration. 20
Water uptake
The water uptake capability is an important parameterfor materials to be used in biomedical applications.
Water uptake was evaluated, in different media, for the
Gellan physical and chemical hydrogels. The physicalhydrogels show a similar behaviour in the different

513

media, meaning that their different composition does notaffect their water uptake: only the physical hydrogel[Gellan 2%] show slightly lower values of theparameters swelling [S] and water uptake ratio [wR],
especially in SGF (Simulated Gastric Fluid, HCl 0.1 M,
pH = 1) solution. This behaviour is probably due to thelow pH environmental conditions, which induce theformation of more stable junction zones. In fact, at pH =1, a suppression of the polyelectrolytic behaviour of
Gellan chains occurs, because the carboxylate groups arein their acidic form. In these conditions the polymer
chains can be closer one another leading to themacroscopic shrinking of the gel. For the chemical
crosslinked samples the water uptake is strongly
dependent both on hydrogel and solution compositions.
As expected, water uptake is inversely proportional tothe crosslinking degree of the sample. When thehydrogels are swollen in water, their behaviour is quite
similar to that of the super-absorbent materials [16],showing very high values of the swelling parameter(e.g., S = 350 for the [Gellan 2% + Lys 0.3]Chem, and S= 1,070 for the [Gellan 2% + Lys 0.1]Chem). In
physiological solution (NaCl 0.9% w/v) and in SIF(Simulated Intestinal Fluid, Phosphate Buffer, pH = 7.4)
the crosslinked and physical hydrogels show low S
values, similar to those of the Gellan gum hydrogels, due
to the presence of a large amount of Na+ counterions
that reduce the electrostatic repulsions among thecarboxylic groups of the polymeric chains, leading to amore compact overall structure. The sample [Gellan 2%+ Lys 0.1]Chem represents an exception to this generalbehaviour: in this case the water uptake is significantly
higher, because the polymer chains are in a random coilconformation (as depicted in the model) and the
network, with a quite low crosslinking degree, is able toabsorb high amounts of water. Again, in SGF, a reduced
water uptake is observed. Similar comments can bemade about the wR parameter. 21

Table 1. wR ratio (weq/w0) for the different hydrogels, swollen in different media at 37 °C.
Water

Sodium Chloride SGF[0.9%w/v}[Gellan 2%]Phys
0.96 ± 0.03
0.99 ± 0.04
0.77 ± 0.02
[Gellan 2% + Lys0.1]Phys
1.03 ± 0.04
1.04 ± 0.03
0.93 ± 0.02
[Gellan 2% + Lys 0.2]Phys
1.02 ± 0.02
1.02 ± 0.04
1.00 ± 0.04
[Gellan 2% + Lys 0.3]Phys
0.99 ± 0.02
1.02 ± 0.02
0.98 ± 0.02
[Gellan 2% + Lys 0.1]Chem
21.95 ± 0.20
1.48 ± 0.03
1.34 ± 0.04
[Gellan 2% + Lys 0.2]Chem
12.98 ± 0.15
1.04 ± 0.02
0.75 ± 0.03
[Gellan 2% + Lys 0.3]Chem
7.06 ± 0.15
0.99 ± 0.04
0.70 ± 0.02
The data are presented as arithmetic mean of three different measurements ± SD.

SIF
0.97 ± 0.02
1.02 ± 0.04
1.03 ± 0.03
1.02 ± 0.04
1.54 ± 0.03
1.02 ± 0.03
0.98 ± 0.02

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)Effects of other natural hydrocolloids on the texturalproperties of gellan gum.
Various studies to find out the changes in the texturalproperties of gellan gum when mixed with other foodhydrocolloids have been carried out.
Sodium alginate
Sodium alginate dissolved in calcium chloride solution
at 900C shows weak gel properties similar to those ofordered xanthan. The solutions show a sharp increase inrigidity on cooling, and convert to permanent gels on
storage at low temperature. The gelsattain maximum
hardness at about 40% calcium conversion (for alginate
with a polyguluronate content of 58%), and theirelasticity can be readily controlled by adjustment of Ca 2+
concentration around this optimum value. Papageorgiou
et al. observed that incorporation of moderateconcentrations of gellan (0.1-0.3%, by mass per volume,in combination with 2%, by mass per volume, alginate
and 5 mM trisodium citrate, increased the strength of thegels, but did not significantly change their elasticity,
indicating that the gellan acts as strong ‘filler’ in an
alginate matrix.22
Gelatin
Lau et al. carried out texture profile analysis on mixedgellan-gelatin gels to assess the effect of the ratio of thetwo components and calcium ion concentration.
Hardness, brittleness, cohesiveness and springiness were
measured. The results suggested that there was a weak
positive interaction between gellan and gelatin when no
calcium was added; at higher concentrations, gellan
formed a continuous network and gelatin the
discontinuous phase. Hardness was dependent on theconcentration of gellan gum in the mixture, whereas
brittleness, springiness and cohesiveness were very
sensitive to low levels of calcium (0-10 mM), but lesssensitive to higher calcium concentrations and gellan/
gelatin ratio.23
Carrageenan and xanthan
Rodriguez-Hernandez and Tecante studied exture
properties of gellan – carrageenan and gellan-xanthan
mixtures in order to determine the contribution of both
polysaccharides to the viscoelastic behaviour of the
mixture. Admixtures having a constant total
concentration of 0.5% (by mass) with different
proportions was prepared in the presence of 0.01 mol/kg
CaCl2. It was observed that gel strength of 0.5% gellanalone was the highest, and gel strength of the twocomponent gels decreased as the proportion of gellan
was reduced. Mixed gels having a gellan concentration
equal to or lower than 50% mass of the total
concentration were less stiff and brittle, hence were moreelastic.24

514

Effect of chelatants on textural properties of gellan
gumCamelin et al. studied the effect of various
concentrations of sequestrants (sodium citrate, sodium
metaphosphate, and EDTA) on gellan gel setting
temperature and rheological properties. Addition of
EDTA between 0 and 0.8% (by mass per volume)
progressively decreased the setting temperature. Citrate
and metaphosphate decreased this parameter when added
up to 0.4 or 0.6%, depending on gellan gum
concentration, eventually resulting in the absence of gel
formation at room remperature for the 1.5% gellansolution containing 0.4% citrate. This effect was
accompanied by a significant decrease of gel strength,
and might be attributed to the binding of divalent cations
required for chain association during gelatinization bychelatants.25
PHARMACEUTICAL APPLICATIONS:In the presence of counterions, this polymer is capable offorming gels that are particularly strong when formed
with divalent ions. The degree of acylation also
influences the strength of the resulting network. Indeed,
when gellan is acylated it forms soft, elastic, transparent
and flexible gels while de-acylation leads to hard, nonelastic and brittle gels.The gels are thermoreversible,
with a melting temperature, Tm, at about 50 0C,
depending on the concentration and presence of cations
that, stabilizing the gel, increase the Tm value. The
polymer, initially used mainly as a food ingredient, hasbeen widely investigated to devise novel ophthalmic
formulations due to its ability to gelify in the presence oftear fluid cations thus providing drug ocularbioavailability. Hydrogels, in fact, show high patientcompliance and in situ forming gels are even preferredsince they are dropped as a solution in the eye where thetransition into a gel actually takes place. Importantparameters, like the gel strength, were studied to find areliable indicator of the gel ocular bioavailability. In vivo
experiments showed that only when the gel strength waswithin set limits, an appreciable increase in ocularbioavailability was obtained. The ocular contact timeincreased with increasing gellan concentration; on theother side, the autoclaving process, carried out tosterilize the gellan solutions, led to a significant
reduction in the finished product of the gel strength due
to a breakdown of the polymeric chains that was
proportional to the autoclaving time. 26 Due to thedecisive role of rapid gel formation in the use of in situgelling systems, contact times with different osmolalities
were measured. As expected, gels formed withhypotonic solutions maintained their integrity for several
hours.

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)Gels of gellan can be formed in the tear fluid even when
the polymer concentration is very low and sodium
proved to be the best gel-promoting ion in vivo though inphysiological conditions the instilled drops are diluted,
gels with a high elastic modulus can be formed. In fact,
dilution of the tear fluid takes place upon instillation of asolution of salt free gellan, but an elastic “skin” isimmediately formed keeping the drops somehow
compacted.27
Gellan has also been tested in vivo for the nasal uptakeof fluorescein dextran used as a model molecule.28 The
starting solution of gellan behaves like a fluid but it
forms a rigid gel when exposed to cations. Hence, it issuitable for nasal spray pumps with its initial low
viscosity and the subsequent gelling upon contact withanimal mucosa. A rapid gelation an also be expected inhumans, the surface area of their nasal cavity being
much larger than that of a rat. Furthermore, incomparison to plain solutions, lower doses can beadministered because of the rapid gelation. Althoughwith divalent cations (Ca2+) the gels are much stronger,in vitro experiments demonstrated that a strong gel isformed in physiological conditions of 0.9% NaCl andthe gel obtained in vivo is strong enough to remain in thenasal cavity for the required time interval, showing aslow clearance due to a higher local concentration.
Gellan has also been tested for the encapsulation of
biological components inside a polyion complex formed
between gellan and chitosan.29 Apart from the sustained
release, the use of capsules and microspheres offers
several benefits. In particular, encapsulated substances
can be protected, the small particle size enabling
repetitive administration either orally or by injection as
therapeutic bolus.
Selection of encapsulation method is crucial in achieving
an encapsulation that allows enzymes and/or peptides toretain their catalytic activity or biological function. The
method by complex coacervation is based on polyioniccomplexation through electrostatic interactions between
cationic and anionic polymers resulting in theformulation of insoluble spherical capsules. It has been
ascertained that gellan-chitosan capsules retain proteinsbut release low-molecular weight substances across thecapsule membrane. Upon loading into the capsules, an
enzyme behaves like a free enzyme. The permeation of
the inner materials is obviously dependent on theirmolecular masses, molecular structures and electricalcharges. Indeed, an exclusion limit for the diffusion outof the membrane has been experimentally found.
Furthermore, it was evidenced that the loaded enzyme
recovered its catalytic activity after the drying andselling steps, indicating that this formulation can be
repeatedly used. Hence, it is a potentially powerful tool
for applications in the field of biotechnology. It should515

be pointed out that both polymers are biodegradable andbiocompatible, thus, the enzyme-encapsulating gellanchitosan capsules can be implanted directly, eliminating
the need for surgical removal because of their bioresorbability. Finally it is important to underline that the
enzyme encapsulating procedure does not need any
chemical modification and can be conveniently
performed in aqueous solution.
Formation of gellan beads has also recently
experimented to evaluate the effect of various divalentcations on the encapsulation efficiency using a constantconcentration of polymer and ionotropic medium. 30 It is
well known that the gelling mechanism of gellan can be
induced by cations and is temperature-dependent. In
aqueous solution the gelation of gellan is accompanied
by a two-step process which involves formation of
double helices from random coil chains (coil-to-helix
transition) and an aggregation of pairs of double helices.
The coil-helix transition is greatly affected by theelectrostatic interaction with the cations present in thesolution. Gellan forms gels in the presence of mono (Na+and K+) and divalent (Ca2+ and Mg2+) cations but its
affinity for the latter is much stronger than for theformer. Preparing hard gelled beads with different
cations has a significant effect on the aqueous solubilityof the drug. Furthermore, drug loading increases as theatomic number of the divalent ion increases, thus
suggesting that the electro-positivity of cations plays animportant role in the ionotropic gelation of gellan.
Although the drug loading efficiency was much higher
in the presence of transition elements compared toalkaline earth metal ions, the beads prepared with Ca2+
were the best in terms of quality and mechanicalstrength.
Gellan has also been tested for oral drug delivery. 31 The
formulation adopted was a gellan solution containing
calcium chloride (as the source of calcium ions) andsodium citrate, which complexes the free calcium ionsand only releases them in the highly acidic environmentof the stomach. The formulation remained in its liquid
form until it reached the stomach where the gelation
occurred after a few minutes and lasted for several
hours. Plasma drug levels, tested after oral
administration of gellan solutions, showed that asustained release was achieved, along with a higher
bioavailability compared to that of a sustained releasecommercial solution product.
In terms of oral sustained delivery, gellan has been
compared to sodium alginate which, as previously
reported, is also capable of giving in situ gelation in theacidic environment of the stomach. The in vivo release
curves from the gels had a profile similar to that of acommercial suspension. The sustained release effect of
the gel formulation was a consequence of the resistanceK.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)of the gel structure to the diffusion of the drug whereasthat of the suspension arose from the reservoir effect of
the suspension particles as they slowly dissolved in theintestine. The gellan gels were detected in vivo for alonger period of time if compared to those formed withalginate, indicating the formation of a mechanicallystronger gel. There is an obvious advantage of using
polymer solutions because such formulations arehomogeneous liquids and do not have the problems that
may be associated with the formulation and oral
administration of suspensions.
Beads prepared with gellan have also been studied inorder to delay the delivery of loaded substances
employed for weed control in agriculture (e.g.
metribuzin) as well as model molecules for drug delivery(theophylline and benzamide)32 Several formulations,containing different amounts of surfactants and/or oil,
were tested. The beads were prepared by adding calcium
ions to homogeneous slurries of the various components.
The presence of the oil in the formulations reduced thepenetration rate of water into the beads leading to adecreased delivery rate. Similar beads, prepared withalginate, showed a slightly faster release than thoseobtained with gellan. Hence, confirming previous
researches, the strength of the gellan gels was higher
than that of alginate, though a quantitative estimation
was not given. It was also pointed out that, when thehydrophilicity of the model molecule was changed using
a molecule more water soluble, a remarkable increase of
the delivery rate was obtained. These results clearly
indicate that, the swelling of the matrix together with thecomposition of the beads played a key role in thedelivery process.
A recent study reports the preparation of microspheres
obtained by the emulsion cross-linking method of gellan
and poly (vinyl alcohol) in the presence of different
amonts of glutaraldehyde as a cross-linking agent and of516

an antihypertensive drug.33 The use of such IPN
improved the mechanical strength obtained when only
gellan was used. The new microspheres were spherical,
with smooth surfaces and with a narrow unimodal size
distribution. By increasing the cross-link density,
microspheres with smaller size were obtained due to theformation of a more rigid network. An increase in theamount of gellan in turn increased the size of
microspheres with the formation of a more crystalline
matrix. Similarly the drug-loaded microspheres also
showed a crystalline dispersion of the drug into thepolymer matrix. In comparison to microspheres preparedwith only gellan, the new IPN microspheres showed ahigher tensile strength. The in vitro studies evidenced
that the drug release rates were higher for microsphereswith a lower amount of gellan, while the different
diffusion media produced differences related to thesolubility of the drug in the two environments 34
GUAR GUM
Guar gum is a naturally occurring galactomannan
polysaccharide; consists of chiefly high molecularweight hydrocolloidal polysaccharide, composed ofgalactan and mannan units combined through glycosidic
linkages and shows degradation in the large intestine due
the presence of microbial enzymes. It contains about
80% galactomannan, 12% water, 5% protein, 2% acidsoluble ash, and 0.7% fat. Guar gum has a molecularweight of approximately 1 million, giving it a highviscosity in solution. The high viscosity of guar gum
results from its high molecular weight and long chain
structure.35, 36, 37
Chemistry of Guar Gum
A guar gum molecule is made up of about 10,000
residues, which are non-ionic polydisperse rod-shaped
polymers (longer than found in locust bean gum).

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)517

Figure 2: Chemical structure of guar gum.

The structure of guar gum is a linear chain of β-Dmannopyranosyl units linked (1→4) with single member
α-D-galactopyranosyl units occurring as side branches. 38
Galactomannan residues which cannot be digested byhuman and animals itself are well fermented by the
microbes in the GI tract, which produce high amounts ofshort chain fatty acids.
Guar gum hydrates well in aqueous solutions, butconcerns about solution clarity, alcohol solubility andimproved thermal stability led to the development of anumber of chemically modified guar gums. On average
three hydroxyl groups are available for derivatization on
D-mannose or D-galactose sugar units in guar gum. The
maximum theoretical degree of substitution (DS) in suchmolecule is three. The substitution of hydroxyl groups
with ethers such as hydroxylpropyl will allow sidegroups extension which may change the solubility andother characteristics of the guar gum. The molar
substitutions (MS) is defined as the average number ofhydroxyl bearing substituents per sugar unit and canexceed three due to the additional availability ofhydroxyl groups.39
Properties of Guar Gum
The most important property of guar gum is its ability tohydrate rapidly in cold water to attain uniform and very
high viscosity at relatively low concentrations. Apartfrom being the most cost-effective stabilizer andemulsifier it provides texture improvement and waterbinding, enhances mouth feel and controls crystal
formation. The main properties of guar gum are: It issoluble in hot & cold water but insoluble in most organic
solvents and has strong hydrogen bonding properties. It
has excellent thickening, emulsion, stabilizing and film
forming properties, excellent ability to control rheology
by water phase management. The viscosity of guar gum
is influenced by temperature, pH, presence of salts andother solids.40

Table 2. Guar Gum Substitution Patterns39

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)Colonic Properties of Guar Gum
Guar gum is being used to deliver drug to colon due toits drug release retarding property and susceptibility to
microbial degradation in the large intestine41, 42. The
anaerobic bacteria that are responsible for the
degradation of guar gum in the colon are Bacteroides
species (B. fragilis, B. ovatus, B. Variabilis, B.
uniformis, B. distasonis and B. thetaiotaomicron). The
gelling property retards release of the drug from thedosage form as well as it is susceptible to degradation in
the colonic environment. Homogenized and diluted fecesfrom human source were incubated with the guar gum toinvestigate the degradation of polysaccharide byintestinal microflora. It produced a rapid decrease inviscosity and fall in pH while no such results wereobserved when it was incubated with autoclaved fecal
homogenates43
It is to be noted that the utility of guar gum as a colonspecific drug delivery carrier is based on its degradationby colonic bacteria. The colon is rich in anaerobic
bacteria. It implies that guar gum in the form of either amatrix tablet or as a compression coat over the drug core
might have been degraded to a larger extent by theaction of anaerobic microbial population of large
intestine44, 45.
Research Work Conducted on Guar Gum
Guar gum is always a favorite agro-based commodity,
attracting wide interest of researchers all over the world.
Following is the research work conducted during the last
10 years on guar gum in many national and international
laboratories to prepare value added products from thisrenewable source of hydrocolloid. Grafting of poly (Nisopropylacrylamide) (PNIPAAm) was carried out onto
Ocarboxymethyl- O-hydroxypropyl guar gum (CMHPG)
in aqueous solutions by using potassium persulfate(KPS) and N,N,N,N′-tetramethylethylene diamine(TMEDA) as the initiation system, resulting in new
stimuli-responsive grafted polysaccharides.
The
resulting grafted polysaccharides showed lower criticalsolution temperatures in aqueous media.46
The rheology of binary mixtures of two alginates andone carboxymethyl guar (CMG) was determined. Tworeactive dyes were printed from pastes based on these 6
mixtures. The printing and the final print (color yield,
levelness and fabric stiffness) were assessed. From theresults, it can be concluded that mixture of CMG withalginates can be used in reactive printing. With a viewthat hydroxypropyl guar (HPG) may replacehydroxyethyl cellulose (HEC) from water based paints,
chemicalmodification
of
guar
gum
via
hydroxypropylation was carried out at lab/commercial
level. The comparative study reveals that HPG is a518

perfect choice of rheological agent, which governs
excellent properties for aqueous paints. This product has
similar/betterproperties
of
HEC.
Graft
copolymerization of methacrylic acid (MAA) onto guar
gum was carried using potassium persulfate (PPS) as
free radical initiator. Using PPS, the maximum percent
grafting was ascertained to be 241 at the optimum
conditions of 60°C reaction temperature, 3 h of reaction
time, 1.1 mmol of PPS and 0.058 mol of MAA. The
prepared graft copolymer could find applications in drugdelivery systems. Chemical modification of guar gum
was carried out through substitution and grafting
reactions and products so obtained were tested against
kaolin suspension to check their efficacy as flocculants.
It was found that flocculation efficiency of thechemically modified products is better than Deftech andhas potential to replace synthetic flocculants. Flocculants
were also synthesized by grafting of polyacrylamide(PAM) onto hydroxypropyl guar gum (HPG) using a
ceric ion-induced solution polymerization technique.
Flocculation efficiency of grafted products wasdetermined against kaolin, iron ore and silica
suspensions. Among the series of graft copolymers, theone with fewest but longest PAM chains shows thebetter performance. Graft copolymerization of various
monomers like N-vinyl-2-pyrrolidone, 4- vinylpyridine,acrylamide and acrylic acid onto guar gum was carriedout by using initiator systems viz. potassium
peroxymonosulfate / glycolic acid, potassium
7monopersulfate / thioacetamide, Cu+2-mandelic acidredox couple and peroxydiphosphate-silver (I)respectively. The effect of different reactants along withreaction time and temperature were studied bydetermining the grafting parameters: grafting ratio,
efficiency, conversion, add-on, homopolymer, and rateof grafting. It was observed that the graft copolymers
were thermally more stable than the pure gum. Guargum / poly (acrylic acid) semi-interpenetrating polymer
network (IPN) Hydrogels have been prepared via free
radical polymerization in the presence of a crosslinker of
N,N′-methylene bisacrylamide (MBA). Hydrogels
showed enormous swelling inaqueous medium and displayed swelling characteristics,
which were highly dependent on the chemicalcomposition of the hydrogels and pH of the medium(ionic strength I = 0.15 mol/L) in which hydrogels were
immersed.47
The water uptake behavior of barium ions crosslinked
sodium alginate/carboxymethyl guar gum bipolymericbeads in the media of varying pH was also studied. The
beads swelled to nearly 15±4% in simulating gastricfluid (SGF) of pH 1.2 in 3 h. On transferring thehydrogel into simulated intestinal fluid (SIF) of pH 7.4,
the swelling was enhanced to nearly 310±12%. When

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)loaded with the model drug vitamin B12, the 8 total
release in SGF in 3 h was nearly 20%, while nearly 70%
was released in SIF in the next 7 h. The percent
entrapment was nearly 50% when the beads werecrosslinked with a 5-6% (w/v) BaCl2 solution. 48
Guar gum was chemically modified by sulphonation
using chlorosulphonic acid (ClSO3H) as a reagent.
Activated partial thromboplastin time (APTT) assay
showed that the guar gum sulphate could inhibit the
intrinsic coagulant pathway. The anticoagulant activity
strongly depended on the degree of substitution (DS) andmolecular weight (Mw) of polysaccharides. DS>0.56
was essential for anticoagulant activity. The guar gum
sulphate with the DS of 0.85 and the Mw of 3.40×104
had the best blood anticoagulant activity. The optimum
reaction conditions for affording maximum percentage
of grafting for grafting of acrylonitrile (AN) onto sodium
salt of partially carboxymethylated guar gum (DS 0.497)
using ceric ammonium nitrate (CAN) as a redox
initiator, in an aqueous medium, by successively varying
reaction conditions such as concentrations of nitric acid,ceric ammonium nitrate, monomer (AN) as well asreaction time, temperature and amount of substrate wasalso established by an expert. The IR-spectroscopic,
thermal (TGA/DSC) and scanning electron microscopic(SEM) techniques were used for the characterization of
the graft copolymer. Using microwave (MW) irradiation
grafting of polyacrylonitrile (PAN) onto guar gum inwater was done without using any radical initiator or
catalyst within a very short reaction time. The extent ofgrafting could be adjusted by controlling the reaction
conditions and maximum percentage grafting (%G) of
about 188% was obtained under optimum conditions in
1.66 minutes.49
Grafting of acrylamide onto guar gum is achieved byCe(IV) induced free-radical polymerization to prepareinterpenetrating polymer network (IPN) beads ofpolyacrylamide-g-guar gum with sodium alginate bycrosslinking with glutaraldehyde. Two widely usedpesticides, solid chlorpyrifos and liquid fenvelarate,
were loaded up 9 to 60-70% efficiency in the IPN beads.
Equilibrium swelling experiments indicate that theswelling of the beads decreases with an increase incrosslinking, as well as an increase in pesticide loading.
The action of a cationic polyelectrolyte (ammoniumhydroxy-propyl-trimethyl chloride of the polysaccharide
guar gum, commercially know as cosmedia guar, CG) inaqueous alumina suspension was investigated. This
polymer was used aiming to find alternatives forsynthetic polymers, as for instance, sodium polyacrylatePANa, normally used as a deflocculating agent ofalumina suspension. The measurements of particle size,
as a function of time, showed that the addition of thispolyelectrolytic macromolecule (CG) keeps the particles

519

dispersed for a longer time, in comparison with thesuspension containing only alumina. The cericammonium-nitrate-initiated graft copolymerization ofpolyacrylamide onto hydroxypropyl guar gum bysolution polymerization technique was studied. The
synthesized products were then characterized by various
instrumental techniques like viscometry, elemental
analysis, IR, thermal, XRD and SEM studies. The
percentage of grafting increases with increasing catalyst
concentration
anddecreaseswithmonomer
50
concentration taking other parameters constant.
A mild method for microencapsulation of sensitive
drugs, such as proteins, employing a suitably derivatizedcarboxymethyl guar gum (CMGG) and multivalent
metal ions like Ca2+ and Ba2+ was reported. The
swelling data of Ca2+ and Ba2+ crosslinked beads
suggest that Ba2+ crosslinks CMGG much more
efficiently than Ca2+. The drug loading efficiency ofthese Ba2+/CMGG beads, as a function of concentrationof both metal ion as well as drug, was then determinedusing Bovine Serum Albumin as a model drug. Results
indicated that Ba2+ crosslinked carboxymethyl guar
gum beads could be used for gastrointestinal drugdelivery.51
The utility of guar gum in the preparation of chemicalgels to be degraded in the large intestine has also been
investigated. A problem arises in its excellent swelling
properties and hydrophilicity, which requires its
protection in the upper part of the GI tract. Cross-linking
with glutaraldehyde has been proven to decrease its
swelling properties.52 Cross-linking density increases
proportionally to increases in the amount of cross-linker,
resulting in a corresponding reduction in solvent uptake.
Guar gum as a hydrogel was not proven suitable withhighly water-soluble drugs due to the resulting very fastdelivery. On the other hand, it is potentially useful withpoorly water-soluble drugs (even with no further
coatings), to act as a specific carrier for colon delivery,
with or without specific enzymes.
A further very recent study has also investigated the
preparation of disc-shaped matrices of guar for colon
specific delivery.53Specifically; the guar gum was again
cross-linked with glutaraldehyde, the chosen model drug
being ibuprofen. The drug loading was accomplished byimmersion of the dried discs of the sample into amethanol ibuprofen solution. This kind of loading is not
usually advisable since only very seldom it is efficientand the amount of drug present in the matrices is usually
very small. Here the release was essentially governed by
the presence of enzymes. Indeed, without an enzymatic
source only a minimal diffusion of the drug was detectedin simulated gastric and intestinal environments. Given
the promising in vivo applications, this kind of network
appears to be potentially quite useful. Nevertheless, aK.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)clear picture of the cross-linking reaction is still lacking
since it is well known that glutaraldehyde is capable ofpolymerizing, making it difficult to know the real lengthof the cross-linking between the macromolecular chains.
Hence, further research is required since this problem
can considerably limit the reproducibility of the samples
that can be obtained. Furthermore, in vivo experiments
have identified the specific group of enzymes capable ofdegrading the matrices of guar cross-linked with sodium
trimetaphosphate.54 By introducing modifications on thepolymeric chain of guar, the dosage forms were preparedcapable of carrying their hydrophobic drug load throughthe proximal portions of the GI tract, while maintaining
their susceptibility to degradation by the colonic
enzymes.
Another useful application of guar has been evidenced in
the treatment of open-angle glaucoma, where guar was
blended with carbopol 940 and sodium alginate.55 The
system was a free flowing liquid with low viscosity
before use, turning into a hydrogel upon contact withartificial tears fluid. Here, the guar specifically increased
the viscosity of the blend, a crucial parameter inobtaining the minimum rate of delivery.
SCLEROGLUCAN;
Scleroglucan is a natural exopolysaccharide produced byfungi of the genus sclerotium (Sclerotium Rolfsii) thathas been extensively studied for various commercial
applications and also shows several interesting
pharmacological properties. The commercial product is

520

termed scleroglucan; but it is also known with othernames according to the company that produces thepolysaccharide (eg: Actigum, clearogel, polytran FS
Sclerogum)[22].Because of its peculiar rheologicalproperties and its resistance to hydrolysis, temperature,and electrolytes, Scleroglucan has various industrial
applications especially in the oil industry for thickening;
drilling mud’s and enhanced oil recovery. Other
industrial use include the preparation of adhesives, watercolors, printing inks, and liquid animal feed
composition.56
In the cosmetic industry, Scleroglucan may be used inhair control compositions and in various skin care
preparations, creams and protective lotions. 57 In
pharmaceutical products Scleroglucan may be used as a
Laxative in tablet coatings and in general to stabilize
suspensions[25].In the food industry numerous Japanese
patents describe quality improvements of frozen foods,
Japanese cakes, steamed foods, rice crackers and bakery
products.58 The use of Scleroglucan as an antitumor,
antiviral and antimicrobial compound has also been
investigated. Sclg has shown immune stimulatory effects
compared with other biopolymers and its potential
contribution to the treatment of many diseases should betaken into account in therapeutic regimens. Recently it
has attractive properties of the polysaccharide incontrolleddrugreleaseandespeciallyin59, 60immunopharmaceutical applications.

Figure: 3.Chemical structure of scleroglucan

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)Scleroglucan is a branched natural homopolysaccharide
that gives only D-glucose after the complete hydrolysis.
The polymer consists of a main linear chain of β-D- (13) - glucopyranosyl units; there is a β-D- glucopyranosyl
unit (1-6) linked to every third unit.61 The structure was
first elucidated by periodic oxidation analysis and later
verified by methylated sugar analysis and 13C nuclear
magnetic resonance (NMR) the chemical structure of thetetrasaccharide repeating unit of sclg as established by
NMR analysis. Sclg chains in aqueous media feature a
triple helical conformation of remarkable stability. The
side chain units can be derivatized by means of selective,
controlled periodate oxidation; the ensuring aldehydegroups oxidized to carboxylate groups thus yielding
polyeclectrolytes of variable, controlled charge densitythat exhibit interesting conformation-dependent solution
properties.
The carboxylated polymer (Sclerox) has been found toassume a single helical conformation in aqueous
solution, the breakage of the triple helix occurs during
the reaction leading to the aldehyde derivative until adegree of substitution equal or less than 40%, the stableconformation of the triple helix is retained, while
introducing a percentage of aldehyde groups of the orderof 50% or more the triple helix disentangles into single
chains. Both Sclg and its oxidized derivatives have been
proposed for the formulation of sustained drug release
dosage forms.62, 63
Solubility:
Scleroglucan disperses rather easily in water at room
temperature due to the presence of β-D-(1-6)glucopyranosyl groups that increase the solubility of thepolysaccharide and decrease the ability to form the gels.
Refined grades of Sclg dissolve readily in hot and cold
water to form pseudoplastic solutions with shear
thinning characteristics that tolerate high temperature,broad range of pH and a variety of electrolytes. 64 The
viscosity of scleroglucan solutions is affected only
slightly by temperature variations. At 0.5 and 2%, it
remains practically constant between 10 and 900C. At
low temperatures, close to 70C, solutions of Sclg form
thermoreversible gels that may be caused by weaklyinteracting triple helix cross-linking mechanism. The
viscosity of Sclg is unaffected over a pH range of 1 to 11
in addition of dimethyl sulphoxide in aqueous solutionsof pH = 12.5 or higher or at temperatures above 900, thereduced viscosity, specific rotation and sedimentationco-efficient indicates disruption of the triple helicalstructure to a single random coil.65 Sclg forms stable gelsin the presence of chromium salts and borax at pH 1011, and can be precipitated by the addition of quaternaryammonium salts under alkaline conditions.

521

Compatibility:
Rehydrated Sclg is compatible with electrolytes such as
5% Sodium chloride, 5% Sodium sulphate, 20%
Calcium chloride and 10%disodium hydrogen
phosphate. However, when the electrolyte concentrations
are very high, solutions may gel and flocculate. Sclg iscompatible, without synergism with most otherthickeners such as locust bean gum, alginates, Xanthan
and Carrageenan and cellulose derivatives and produces
most favorable properties to modify the drug release invarious pharmaceutical products.66
Rheology:
Pseudoplasticity or shear thinning is the salient
characteristic of Scleroglucan solutions. This is evident
in the gum solutions of 0.2% or lower but the flow
becomes progressively more Newtonian as theConcentration decreases below 0.2%. Solutions
containing less than 0.8% of scleroglucan are notsignificantly thixotropic except at temperatures dropping
to 100 and below. Due to high degree of
Pseudoplasticity, gel states are not always clearly
defined. Thus 1.2 – 1.5% solutions of purified gum form
self-supporting sliceable gel at approximately 250 but attemperatures below 100, even much diluted solutions,from diffusely structured gels that tend to shrink andundergo synergism when left undisturbed for long
periods of time. Such diffused gels disperse quickly withmild agitation. 67
Suspending Properties:
A pseudoplastic flow system enherently combines acapacity for suspending fine particles with goodpourability of suspension. Purified Scleroglucan at 0.1 –
0.2% effectively stabilizes 5-10% aqueous suspensionsof fine powders such as Zinc-oxide, reprecipitatedcalcium carbonate and sulphamerazine. The viscosity of
combinations of scleroglucan with bentonite suspensions
is markedly synergistic. Thus, while the apparent
viscosities of 0.15% of purified gum and 5% bentonite
are around 200 and 300 cps respectively, a combinationof the two yields the viscosity of > 4000 cps. Although
not a primary emulsifier in the sense of a surfactant Sclg
enables very low energy dispersion during the formationof stable oil-in-water emulsions. In addition to thesuspending action of the pseudoplastic system,
prevention of coalescence seems to underlie this kind ofstabilization 68
PHARMACEUTICAL APPLICATIONS OF
SCLEROGLUCAN:
Pharmaceutical applications include the use in tablet
coatings, ophthalmic solutions, injectable antibiotic
suspensions and calamine lotion. Another important use

K.M.Manjanna et al /Int.J. ChemTech Res.2010,2(1)522

of scleroglucan is in the form of carboxylated derivative
for use as a matrix for drug delivery in the form oftablets or films. For this purpose, hydrogels obtained by
the crosslinking reaction between the polycarboxylated
derivative of scleroglucan and alkane dihalides were
evaluated for the diffusion experiments and water uptake69 Here scleroglucan offers advantages of controlled
release as well as compatibility, biodegradability, andbioadhesiveness and thermal and chemical stability. The
peculiar physicochemical properties of scleroglucan
suggested its suitability as a slow a remarkable swelling
process that can slow down the diffusion of molecules
previously loaded in the system. Furthermore, during thehydration process, the formation of a swelled layer slows
down the penetration of the dissolution medium. This
layer therefore represents the rate-limiting step of water
penetration, which is very important for the release ofmodel drugs. Coviello et al 70 reviewed the use ofscleroglucan and some derivatives in the field ofpharmaceutics and in particular for the formulation ofmodified release dosage forms. The native scleroglucan
can be used for the preparation of sustained releasetablets and ocular formulations; oxidized and crosslinked scleroglucan can be used as a matrix for dosage
forms sensitive to environmental conditions. Anotherinteresting approach is the preparation of a co-crosslinked network using aqueous medium instead of theusual organic solvents and gellan as cross-linker. At the
beginning only physical entanglements between the
different chains are effective; the network is
subsequently “frozen” via chemical bonds, leading to areal physical-chemical gel with an improved stability.
This new polymeric network showed a sustained release
behavior that was better modulated than that obtainedwith the single polysaccharide 71
Scleroglucan is one very clear example of a polymer
whose microscopic structure corresponds to specific andpeculiar properties of the macroscopic swelling behaviorof the matrix. The exopolysaccharide can form gels in

the presence of borate ions, showing a mixed networkwith both chemical and physical linkages between the
cross-linker and the chains. According to the molecular
dynamics approach, the rigid rods are almost forced toalign and to form bundles in which the borate acts
almost as a “Zipper”. Cavities along the chains are thus
formed that can allocate host molecules in function of
their steric hindrance. This microstructure is obviously atthe origin of the release profiles observed in vitro ofdifferent model drugs. It is also behind the unusual andanisotropic swelling found in the case ofscleroglucan/borax tablets.72

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