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XANTHAN GUM; ITS BIOPHARMACEUTICAL APPLICATIONS: AN
OVERVIEW
Abdulsalam Alhalmi1*, Nafaa Alzubaidi2, Marwan Altowairi3, Marwan Almoiliqy3 and
Bharti Sharma3
1College of Pharmacy, University of Aden, Yemen. Faculty of Pharmaceutical Sciences,
PCTE Group of Institutes, Ludhiana, India.
2Department of pharmacy practice, Jamia Hamdard University, New Delhi, India.
3Faculty of Pharmaceutical Sciences, PCTE Group of Institutes, Ludhiana, India.
ABSTRACT
Polysaccharides have been finding, in the last decades, very interesting
and useful applications in the biomedical and, specifically, in the
biopharmaceutical field. Xanthan gum is a natural polysaccharide,
produced by the bacterium Xanthomonas campestris. This polymer
displays a number of appealing characteristics for biopharmaceutical
applications, among which its high thickening capacity should be
highlighted. In this review, we describe critical aspects of xanthan
gum, contributing for its role in biopharmaceutical applications.
Physicochemical properties, production, as well as strong and effective
synergies with other biomaterials are described. The specific
biopharmaceutical applications are discussed.
KEYWORDS: Controlled release, gelling capacity, xanthan gum, polysaccharides, synergy.
INTRODUCTION
Polymers are widely used in pharmaceutical dosage forms, which include both synthetic as
well as natural polymeric materials.[1] The natural polymers such as natural gums are
biocompatible, biodegradable, cheap and easily available and are preferred to synthetic
polymers because of their low cost, lack of toxicity, availability and non irritant nature.[2] On
the other hand, they have some limitations, such as the highest possibility of immunogenicity
and polymer variability related to both origin and supplier.[3]
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 6.647
Volume 7, Issue 1, 1536-1548 Review Article ISSN 2278 – 4357
Article Received on
18 Nov. 2017,
Revised on 09 Dec. 2017,
Accepted on 30 Dec. 2017,
DOI: 10.20959/wjpps20181-10869
*Corresponding Author
Abdulsalam Alhalmi
College of Pharmacy,
University of Aden,
Yemen. Faculty of
Pharmaceutical Sciences,
PCTE Group of Institutes,
Ludhiana, India.
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Abdulsalam et al. World Journal of Pharmacy and Pharmaceutical Sciences
The plant based polymers have been studied for their application in different pharmaceutical
dosage forms like matrix controlled systems, microspheres, nanoparticles, film coating
agents, buccal films, viscous liquid formulations like ophthalmic solutions, suspensions,
implants and their applicability and efficacy has been proven. These also have been utilized
as viscosity enhancers, solubilizes, stabilizers, disintegrates, emulsifiers, gelling agents and
bioadhasives, binders in different dosage forms.[4]
The xanthan gum is a high molecular weight hetero polysaccharide gum produced by a pure
culture fermentation of a carbohydrate with the microorganism Xanthamonas campestris.[5]
Xanthan gum is a hetero polysaccharide consisting mainly of repeating unit of
pentasaccharide formed by two glucose units, two mannose units, and one glucuronic acid
unit, in the molar ratio 2.8:2.0:2.0 (Fig.1).[6]
The basic fundamental unit of polysaccharides is the monosaccharide D-glucose although D-
fructose, D-galactose, L-galactose, D-mannose, L-arabinose, and D-xylose. Some
polysaccharides include monosaccharide derivatives in their structure, like the amino sugars
D-galactosamine and D-glucosamine, as well as their derivatives N-acetylmuramic acid and
N-acetylneuraminic acid, and simple sugar acids (iduronic and glucuronic acids). In some
cases, polysaccharides are collectively named for the sugar unit they contain, so glucans are
given for glucose-based polysaccharides, while mannans are given for mannose-based
polysaccharides.[7]
Xanthan is one of the most extensively investigated polysaccharides.It has been widely used
in oral and topical formulations, cosmetics and foods as suspending or stabilizing agent,
thickening, emulsifying, film forming and gelling nature and release control agent in
hydrophilic matrix formulations.[8,9]
This natural polymer has been investigating increased interest in the biopharmaceutical field,
particularly in oral drug delivery. It has been showing its application in the design of drug
delivery systems, providing the delivery of a defined dose, at a predetermined rate, to a
targeted biological site. In this review, critical aspects of xanthan gum are exposed, with
particular discussion on the physicochemical properties that affect its biopharmaceutical
application. The most effective synergies interactions with other polysaccharides are
described and the reported biopharmaceutical applications are explored and discussed.
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Xanthan Gum, Description and Source
Xanthan gum is a natural high molecular weight polysaccharide, produced from the
bacterium Xanthomonas campestris found on cabbage plants.[10] Xanthan gum powder is free
flowing white to cream coloured soluble in hot and cold water, but insoluble in most organic
solvents. Xanthan gum solutions show a high degree of viscosity in comparison with other
polysaccharide solutions even at low concentrations. This property makes it more effective as
thickener and stabilizer. Xanthan gum solutions are highly pseudoplastic but not thixotropic.
The pseudoplasticity of xanthan gum enhances sensory qualities in final products, eases
processing and ensures a good pourability. Xanthan gum solutions are pH-variations
resistant, i.e. they are stable in both acidic and alkaline conditions. In addition, xanthan gum
has thermal stability that makes it superior to most other water soluble polysaccharides.
Xanthan gum is tasteless and does not affect the taste of other food ingredients.[11]
Chemical Structure and Physicochemical Properties
Xanthan gum is a high molecular weight polysaccharide produced by pure culture aerobic
fermentation of carbohydrate with Xanthomonas campestris bacteria.[12] It is a long chained
polysaccharide with large number of trisaccharide side chains. The main chain consists of β-
(1, 4)-linked D-glucose units (Fig.1). The side chains are composed of two mannose units
and one glucuronic acid unit attached with alternate glucose residues of the main chain. The
terminal D-mannose residues may carry a pyruvate function and the distribution of such
group in the chemical structure is dependent on the bacterial strain and the fermentation
conditions. The non-terminal D-mannose unit in the side chain contains an acetyl function.
The anionic property of this polymer is due to the presence of both pyruvic acid and
glucuronic acid groups in the side chain.[13-14] Xanthan gum is a cream colored powder that is
soluble in hot or cold water with high viscosity even at low concentrations. Xanthan gum has
been extensively investigated as a possible polymeric material in diverse floating drug
delivery technology in addition to being used as gelling agent, stabilizing agent, suspending
agent, and viscosity increasing agent.[15] For example, formulation and evaluation of
rosiglitazone maleate[16], acyclovir[17], propranolol hydrochloride[18], and tapentadol
hydrochloride[19] were done using xanthan gum.
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Table 1. Typical physical properties of commercial xanthan gum.[20]
Property
Value
Physical state
Dry, cream-colored powder
Moisture (%)
8-15
Ash (%)
7-12
Nitrogen (%)
0.3- 1.0
Acetate content (%)
1.9-6.0
Pyruvate content (%)
1.0 - 5.7
Monovalent salt (g L-1 )
3.6-14.3
Divalent salt (g L-1 )
0.085-0.17
Viscosity (cp)
13-35
Figure. 1: Chemical structure of xanthan gum.
Production of Xanthan Gum
The biosynthesis of microbial hetero polysaccharides such as xanthan is a complicated
process involving a multi-enzyme system. The initial step in the biosynthesis of xanthan is
the uptake of carbohydrate, which may occur by active transport or facilitated diffusion. This
is followed by phosphorylation of the substrate with a hexokinase enzyme that utilizes
adenosine 5’-triphosphate. The biosynthesis involves conversion of the phosphorylated
substrate to the various sugar nucleotides required for assembly of the polysaccharide
repeating unit through enzymes such as UDP-Glc pyrophosphorylase. UDP-glucose, GDP-
mannose and UDP-glucuronic acids are necessary for the synthesis of xanthan with the
appropriate repeating unit. In the biosynthesis of xanthan gum on the cabbage plant by
xanthomonas campestris, the cabbage provides the carbohydrate substrates, proteins and
minerals for cell growth. In the laboratory conditions or commercial fermentation, carbon
sources, nitrogen sources, trace minerals and pH conditions are provided in a way that
simulates natural conditions.[21,22]
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Compatibility of Xanthan Gum With other Ingredients
Xanthan gum is compatible with most food, cosmetic and pharmaceutical ingredients.
Xanthan gum is stabile in the presence of acids. It can be dissolved directly in many acid
solutions. Xanthan gum solutions have unusually good compatibility and stability in the
presence of most salts. The addition of electrolytes, such as sodium and potassium chloride,
increases the viscosity and stability. Also divalent salts like calcium or magnesium have a
similar effect on viscosity with optimum viscosity is reached at salt concentrations above
0.1%. Higher salt concentration levels do not affect the rheological properties any further, nor
do they increase stability of xanthan gum solutions. Most food systems contain the
appropriate amount of salts. Even at high concentrations xanthan gum is compatible with
most salts. Xanthan gum tends to form gels at high pH-levels (pH > 10) in the presence of
high concentrations of divalent cations. Trivalent cations, such as aluminum and iron, form
gels at acid or neutral pH. Gelling may be prevented by high levels of monovalent metal salts.
Xanthan gum is anionic polymer exhibits three desirable properties: high viscosity at low
concentrations, pseudoplasticity; and insensitivity to a wide range of temperature, pH and
electrolyte variations. Because of its special rheological properties, xanthan is widely used in
food, cosmetics, pharmaceuticals, paper, adhesives, paint, textiles, oil and gas industry. The
good flow properties of xanthan, in addition with its stability to salts and extremes of pH
levels, give it a technical advantage over most polymers used in drilling. By mixing different
gums with xanthan gum, varying the ratio and the concentration of the combination, result in
very specific characteristics of the end product may be obtained, e.g. viscosity,
pseudoplasticity, texture and mouth feel. Due to the nature of the sugar linkages as well as to
the presence of side chain substituents on the polysaccharide structure backbone, xanthan
gum is highly resistant to enzymatic degradation. Pure xanthan gum can be safely used in the
presence of most enzymes commonly occurring such as galactomannanases, pectinases,
cellulases, proteases, amylases etc. Xanthan gum is not directly soluble in most organic
solvents. Up to 40 - 50 % of common solvents such as isopropanol, methanol, ethanol or
acetone can be added to aqueous solutions of xanthan gum without precipitation of the
gum.[11,23]
Synergy with Locust Been Gum
Xanthan gum produces high viscosity solutions at low concentration, but it does not naturally
gel at any concentration, being insensitive to a broad range of pH, temperature, and
electrolyte concentration.[24] These weak gel properties are known to be enhanced by the
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presence of certain b-(1, 4) linked polysaccharides, which normally exist in water solution as
random coils and in the condensed phase as stiff, extended ribbons, like the galactomannans.
The synergy between xanthan gum and LBG is the most effective and results in a firm,
thermo reversible gel.[25] A synergic behavior was observed even in dilute gum solution.26
The synergistic interaction between the two polysaccharides was reported by Rocks, he
observing the formation of a thermally reversible gel.[27]
Other studies indicated that the synergistic interaction occurs due to the interaction between
the side chains of xanthan and the backbone of locust been gum as in a lock-key model, in
which one xanthan chain could associate with one, two, or more locust bean gum
molecules.[28] A study using X-ray diffraction suggested that in order for the binding between
both polymers to occur, it required denaturation of xanthan at temperatures exceeding the
helix–coil transition temperature, leading to strong elastic gels. Furthermore, it was reported
that when the two polymers were mixed in the same weight ratio, stronger gels, in terms of
hardness and elastic modulus were obtained. The same study also suggested that the
association interaction between xanthan and locust been gum occurred because of disordered
xanthan chains.[29] In contrast, a work with calorimetry and rheological methods revealed that
the association interaction between the polysaccharides was triggered by xanthan
conformational changes.[30] The interaction between the polymers was later reported to be
mediated by two distinct mechanisms. First mechanism takes place at room temperature,
results in weak gels, and presents little dependence upon the galactose content. The second
mechanism requires heating of the polymeric mixture to significant temperature and results in
stronger gels, which formation is highly dependent upon the specific galactomannan
composition.[31] There are reports on the dependence of gelation upon the temperature of
reaction and the specific mannose /galactose ratio of galactomannan. For low galactose
contents, such as that of locust been gum, interactions have been described at temperatures
usually higher than 45°C.[28] Another study demonstrated that the stability of xanthan helical
structure or xanthan chain flexibility played a critical role in the interaction with locust been
gum. It was shown that the deacetylation and heating of xanthan helical structure facilitated
the intermolecular binding between xanthan and locust been gum. However, a study in dilute
solution conditions suggested that the synergy is a result of a conformational change of the
complex xanthan-locust been gum, in which locust been gum should play a significant
role.[32]
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A more recent work studied the possibility of modulating the gel mechanical properties by
varying the polymeric ratios and the temperature of reaction, xanthan chain conformation
being known to be affected by temperature of reaction. It was observed that a LBG/ xanthan
ratio of 1:1 always produces a gel, while a ratio of 1:3 results in a weak gel at 75°C and a
ratio of 1:9 never results in the formation of a real gel. These results indicated that the
properties of the complex polysaccharide gel might be controlled by varying the preparation
temperature and/or the weight ratio between the two polymers.[33]
As can be seen, information on xanthan gum/locust been gum synergy and gelling
mechanism is varied. In fact, although many efforts continue to elucidate the interaction, with
some recent works providing new evidences, a wide debate is still open in the subject. The
synergy interaction between both polymers is so effective that gels have been proposed in
pharmaceutical applications for retard release purposes and tablet formulations already exist
comprising of this polysaccharides.[34]
Biopharmaceutical Applications of Xanthan Gum
The application of natural polymers in pharmaceutical formulations is extremely varied,
comprising the production of solid monolithic matrix systems, films, implants, beads,
nanoparticles, microparticles, inhalable, and injectable systems. Within these dosage forms,
polymeric materials have different roles such as binders, matrix formers, drug release
modifiers, coatings, viscosity enhancers, stabilizers, emulsifiers, suspending agents,
disintegrators, solubilizers, gelling agents, and bioadhesives. Owing to particular features of
xanthan gum specifically related with its gelling ability and synergies with other
polysaccharides, a promising interest is being observed regarding its biopharmaceutical use.
The properties that enable the application of xanthan gum in pharmaceutical applications are
emulsifying, thickening, stabilising, film forming and gelling nature.[35] In this review paper
we focuses on investigating the application of xanthan gum in different drug carrier systems
and its efficacy in targeted drug delivery.
Liposomes
Chitosan is a natural polymer that is used to increase vesicle stability, in a particular study; a
poly anionic compound xanthan gum is allowed to undergo macromolecular complexation
with a chitosan polycationic compound and is studied for its effectiveness in increasing the
vesicle stability synergistically. The result of study was found that liposomal formulation for
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pulmonary delivery have a positive effect by the liposome coating with polyelectrolyte
complex formed by xanthan gum and chitosan complexation.[36]
Hydrogel: Xanthan gum form superporous hydrogels that are cross linked very lightly in
order to enhance the swelling and absorption ability to a higher extent. Rapid absorption of
water takes place in the macromolecular structure through permeation and capillary action.
Sunny et al. have mentioned the synthesis of super porous hydrogels, using xanthan gum,
hydroxyethylmethacrylate and acrylic acid by free radical graft polymerization method.[37] It
was observed that xanthan gum does not form hydrogels readily but are only formed when
the aqueous solutions are annealed to a particular temperature and cooled suddenly.[38]
Matrix Systems: Xanthan gum is used in gum based sustained release tablets, not only
retards drug release, but can also result in time independent release kinetics with added
advantage of compatibility and inertness.[39] Jackson et al. reported that when xanthan gum
and ethyl cellulose were used in matrix tablets used in colon drug delivery, higher
concentration of xanthan gum showed more drug retarding capability than the formulation
with ethyl cellulose.[40] Sourabh Jain et al. reported that cumulative drug release percent was
decreases with increasing gum concentration. In one study, it was also found out that xanthan
gum showed higher ability to retard the drug release than synthetic hydroxypropyl methyl
cellulose.[41]
Niosomes: Shinde et al. observed that when xanthan gum was used in the preparation of
niosomes result in good spreadability there was change in the particle size also reported
compared to the formulation without using xanthan gum and the niosomal formulation
showed pseudoplastic behaviour. He was also found that the physical stability to be more in
formulation containing xanthan gum and even though at higher temperature there is chance of
enzyme leakage from gels, it was observed that chance of enzyme leakage from gels was less
when the niosomal formulation is converted to gel with the use of xanthan gum. Thus it was
experimentally proved that xanthan gum can be used as a gelling agent in the preparation of
serratiopeptidase noisome gel.[42]
Nanoparticles: Polysaccharide nanoparticles can be synthesised by means of covalent cross
linking, ionic cross linking, poly electrolyte complexation etc.,[43] Pooja et al., investigated on
the usage of xanthan gum as reducing agent in the synthesis of gold nanoparticles. These
nanoparticles are involved in drug delivery because of their size and efficient targeted drug
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release. It was found that the gold nanoparticle synthesized using xanthan gum was non-toxic
and biocompatible in the hemolysis study. They also showed high drug loading, stability and
enhanced cytotoxicity in lung cancer cells.[44] In another a study it was also reported that the
viscoelastic gel formed by the synergistic interaction of xanthan gum and guar gum mixtures
can lead to the stabilisation of micro and nano scale iron particles.[45]
Microspheres: In a study conducted by Deshmukh et al., it was reported that when
hydrophilic gums such as xanthan gum and locust bean gum were used, it helped in extending
the drug release time in microspheres of calcium alginate formed by ionotropic gelation
method. It was observed that the drug entrapment efficiency with increase in the
concentration of hydrophilic polymers. The steps involved in the release of drug from
polymer drug matrix are penetration of solvent in to the matrix, polymer gelation, drug
dissolution and diffusion of drug through the different layers.[46]
CONCLUSION
Xanthan gum has been successfully used by many investigators for various approaches in
drug delivery system. Natural polymer like xanthan gum play vital role in different
formulation of drug delivery system. Different drug carrier systems was developed in order to
improve efficacy in drug delivery system so that degradation of drug during transport, toxic
effects due to rapid release can be avoided and better drug transport to the target sites can be
achieved. This also helps in reducing the side effects associated with conventional drug
delivery techniques. In all the above discussed formulations controlled release,
biocompatibility and biodegradability was observed which makes it convenient to be used in
pharmacological applications. Thus targeted delivery aids not only in maintaining the
therapeutic benefits but also in avoiding the overall toxic effects associated with the
conventional approaches.
CONFLICT OF INTEREST
The authors confirm that this article content has no conflicts of interest.
ACKNOWLEDGEMENT
Great thanks to the Faculty of Pharmaceutical Science, Aden University, for providing the
required facilities for the completion of this article.
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