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Indian Journal of Pharmaceutical Education and Research Association of Pharmaceutical Teachers of India
INTRODUCTION
The traditional use of excipients in drug formulations was to
act as inert vehicles to provided necessary weight,
consistency and volume for the correct administration of the
active ingredient, but in modern pharmaceutical dosage forms
they often fulfill multi-functional roles such as modifying
release, improvement of the stability and bioavailability of
the active ingredient, enhancement of patient acceptability
and ensure ease of manufacture. New and improved
excipients continue to be developed to meet the needs of 1,2advanced drug delivery systems .
Polymers have been successfully investigated and employed
in the formulation of solid, liquid and semi-solid dosage
forms and are specifically useful in the design of novel drug
delivery systems. Both synthetic and natural polymers have 3been investigated extensively for this purpose . Synthetic
polymers are toxic, expensive, have environment related
issues, need long development time for synthesis and are
freely available in comparison to naturally available
polymers. However the use of natural polymers for
pharmaceutical applications is attractive because they are
economical, readily available, non-toxic and capable of
chemical modifications, potentially biodegradable and with
few exceptions and also biocompatible.
A large number of plant-based pharmaceutical excipients are
available today. Many researchers have explored the
usefulness of plant-based materials as pharmaceutical excipients. Ability to produce a wide range of material based
on their properties and molecular weight, natural polymers
became a thrust area in majority of investigations in drug 4delivery systems . Natural gums can also be modified to meet
the requirements of drug delivery systems and thus can
compete with the synthetic excipients available in the market 5.
The fact for increase in importance of natural plant based
material is that plant resources are renewable and if cultivated
or harvested in a sustainable manner, they can provide a 6constant supply of raw materials . However, substances from
plant origin also pose several potential challenges such as
being synthesized in small quantities and in mixtures that are
structurally complex, which may differ according to the
location of the plants as well as other variables such as the
season. This may result in a slow and expensive isolation and
purification process. Another issue that has become
Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
Amelia M. Avachat*, Rakesh R. Dash and Shilpa N. Shrotriya
Sinhgad College of Pharmacy, 44/1, Vadgaon(Bk.), Pune-411041, Maharashtra, India
All pharmaceutical dosage forms contain many additives besides the active ingredients to assist manufacturing and to obtain the desired effect
of the pharmaceutical active ingredients. The advances in drug delivery have simultaneously urged the discovery of novel excipients which are
safe and fulfill specific functions and directly or indirectly influence the rate and extent of release and /or absorption. The plant derived gums and
mucilages comply with many requirements of pharmaceutical excipients as they are non-toxic, stable, easily available, associated with less
regulatory issues as compared to their synthetic counterpart and inexpensive; also these can be easily modified to meet the specific need. Most
of these plant derived gums and mucilages are hydrophilic and gel- forming in nature. Recent trend towards the use of plant based and natural
products demands the replacement of synthetic additives with natural ones. Many plant derived natural materials are studied for use in novel
drug delivery systems, out of which polysaccharides, resins and tannins are most extensively studied and used. This review discusses about the
majority of these plant-derived polymeric compounds, their sources, extraction procedure, chemical constituents, uses and some recent
investigations as excipients in novel drug delivery systems.
KEYWORDS: Plants, gums, mucilage, sustained release, novel drug delivery systems.
Revised: 1/7/2010Submitted: 21/4/2010 Accepted: 19/9/2010
Address for Correspondence:
Dr. (Mrs.)Amelia M. Avachat, Sinhgad College of Pharmacy, 44/1, Vadgaon(Bk.), Pune-411041, Maharashtra, India
E- mail:prof [email protected]
86
ABSTRACT
Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
7,8increasingly important is that of intellectual property rights .
The plant based polymers have been studied for their
application in different pharmaceutical dosage forms like
matrix controlled system, film coating agents, buccal films,
microspheres, nanoparticles, viscous liquid formulations like
ophthalmic solutions, suspensions, implants and their 9-11applicability and efficacy has been proven . These have also
been utilized as viscosity enhancers, stabilisers, disintegrants,
solubilisers, emulsifiers, suspending agents, gelling agents
and bioadhesives, binders in the above mentioned dosage 12forms .
Sustained drug delivery systems significantly improve
therapeutic efficacy of drugs. Drug-release-retarding
polymers are the key performers in sustained release drug
delivery system for which various natural, semi-synthetic and 13synthetic polymeric materials have been investigated .
Besides this several polymers are often utilized in the design
of novel drug delivery systems such as those that target
delivery of the drug to a specific region in the gastrointestinal
tract or in response to external stimuli to release the drug.
Most of the investigations of polymers in novel drug delivery 14are centered on synthetic polymers such as ethyl cellulose ,
15 16hydroxypropylmethylcellulose and eudragit . But
individually when they have shown specific limitations,
different combinations like ethyl cellulose and hydrogenated 1 7 1 8castor oil , eudragit and ethyl cellulose ,
19hydroxypropylmethylcellulose and polyamide have been
tried to obtain desired drug release profiles. These
combinations have ultimately found to make the process
complicated and increase the cost of formulation. Recent
trend towards the use of vegetable and nontoxic products
demands the replacement of synthetic additives with natural
one. Many natural polymeric materials have been
successfully used in sustained-release tablets. These
materials include: guar gum, isapghula husk, pectin,
galactomannon from Mimosa scabrella , Gleditsia
triacanthos Linn (honey locust gum) , Sesbania gum ,
mucilage from the pods of Hibiscus esculenta , tamarind seed
gum , gum copal and gum dammar, agar, konjac, chitosan etc. 20.
Natural gums and mucilage are composed of many
constituents. In several cases, the polysaccharides, resins or
the tannins present in the gum are responsible for imparting
release retardant properties to the dosage form. Gums are
obtained from various parts of the plants. In some of the gums
the source may be the epidermis of the seed while on the other
hand it may be extracted from the leaf or bark.
This review gives an insight of plant based novel drug-
release-retarding materials which have been recently studied
as carriers not only in the conventional sustained release
dosage forms but also in buccal drug delivery systems,
gastroretentive systems and microcapsules. Specific
reference thus is made to the use of natural polymers in the
design of novel dosage forms as well as other new drug
delivery systems under investigation.
POLYSSACHARIDES:
Tamarind Gum:
Tamarind xyloglucan is obtained from the endosperm of the
seed of the tamarind tree, Tamarindus indica, a member of the 21evergreen family . Tamarind Gum, also known as Tamarind
Kernel Powder (TKP) is extracted from the seeds. The seeds
are processed in to gum by seed selection, seed coat removal,
separation, hammer milling, grinding and sieving. Tamarind
gum is a polysaccharide composed of glucosyl : xylosyl :
galactosyl in the ratio of 3:2:1 . Xyloglucan is a major
structural polysaccharide in the primary cell walls of higher
plants. Tamarind xyloglucan has a (1 4)-β-D-glucan
backbone that is partially substituted at the O-6 position of its
glucopyranosyl residues with α-D-xylopyranose. Some of the 22
xylose residues are β-D-galactosylated at O-2 .
It is insoluble in organic solvents and dispersible in hot water
to form a highly viscous gel such as a mucilaginous solution 23,24with a broad pH tolerance and adhesivety . Tamarind gum
is non Newtonian and yield higher viscosities than most
starches at equivalent concentrations. This has led to its
application as stabilizer, thickener, gelling agent and binder in
food and pharmaceutical industries. In addition to these, other
important properties of tamarind seed polysaccharide (TSP)
have been identified recently. They include non-25 26carcinogenicity , mucoadhesivity, biocompatibility , high
27 24drug holding capacity and high thermal stability . This has
led to its application as excipient in hydrophilic drug delivery 25-27system .
Magnetic microspheres of tamarind gum and chitosan were
studied. The magnetic microspheres were prepared by suspension cross-linking technique. Microspheres formed
were in the size range of 230 - 460 µm.The magnetic material used in the preparation of the microspheres was prepared by precipitation from FeCl and FeSO solutionsin basic medium 3 4
28.
In another study Diclofenac sodium matrix tablets containing
TSP was investigated. The tablets prepared by wet
Amelia et al.: Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
87Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
granulation technique were evaluated for its drug release
characteristics. The result of this study demonstrated, that
isolated TSP can be used as a drug release retardant. It was
observed that the swelling index increased with the increase
in concentration of TSP. Increase in polymer content resulted
in a decrease in drug release from the tablets. The drug release
was extended over a period of 12 hrs. and followed zero order 29kinetics .
TSP was also examined for its sustained release property
using both water soluble (acetaminophen, caffeine,
theophylline and salicylic acid) and water insoluble drugs 30(indomethacin) . The release rates from the TPS matrix
tablets were found to be dependent on the drug solubility.
Zero order release was achieved for indomethacin from TSP.
Mucoadhesive buccal patches using tamarind gum as
mucoadhesive polymer for controlled release of
benzydamine (BNZ) and lidocaine (LDC) were prepared and 31evaluated . A LDC-tannic acid complex was also prepared
and tested. The patches, prepared by compressing appropriate
mixtures containing the drug salts/complexes, lactose and
tamarind gum, were tested in vitro for mucoadhesion and drug
release, and in vivo on human volunteers for retention and
release of BNZ. The devices containing the salts of BNZ with
pectin and polyacrylic acid, and the complex of LDC with
tannic acid showed zero-order release kinetics in vitro. The
patches adhered for over 8 h to the upper gums of the
volunteers, and were perfectly tolerated. BNZ hydrochloride
was released in vivo and in vitro with practically identical
profiles.
Hibiscus rosasinensis:
Hibiscus rosa-sinensis Linn of the Malvaceae family is also
known as the shoe-flower plant, China rose, and Chinese 32,33hibiscus . The fresh leaves of Hibiscus rosa-sinensis Linn
are collected, washed with water to remove dirt and debris,
and dried. The powdered leaves are soaked in water for 5-6 h,
boiled for 30 min, and kept aside for 1 h for complete release
of the mucilage into water. The material is squeezed from an
eightfold muslin cloth bag to remove the marc from the
solution. Acetone is added to the filtrate to precipitate the
mucilage in a quantity of three times the volume of the total
filtrate. The mucilage is separated, dried in an oven at a
temperature < 50 °C, collected, dried-powdered, passed
through a sieve (number 80), and stored for further use in 34desiccators .
The plant contains cyclopropanoids, methyl sterculate,
methyl-2-hydroxysterculate, 2-hydroxysterculate malvate,
and β-rosasterol. Mucilage of Hibiscus rosa-sinensis contains
L-rhamnose, D-galactose, D-galactouronic acid, and D-35glucuronic acid . The leaves are used in traditional medicines
as emollients and aperients to treat burning sensations, skin 36disease, and constipation .
In a study the use of its mucilage for the development of 34sustained release tablet has been reported . Matrix tablet
containing dried mucilage and diclofenac sodium (DS) was
prepared through direct compression techniques. It was found
that mucilage can be used as release-retarding agent for 12 h
when the drug-mucilage ratio was 1:1.5.
Okra gum:
Okra gum, obtained from the fruits of Hibiscus esculentus, is
a polysaccharide consisting of D-galactose, L-rhamnose and 37 38L-galacturonic acid . Okra gum is used as a binder .
In a study okra gum has been evaluated as a binder in 39paracetamol tablet formulations . These formulations
containing okra gum as a binder showed a faster onset and
higher amount of plastic deformation than those containing
gelatin. The crushing strength and disintegration times of the
tablets increased with increased binder concentration while
their friability decreased. Although gelatin produced tablets
with higher crushing strength, okra gum produced tablets
with longer disintegration times than those containing gelatin.
It was finally concluded from the results that okra gum maybe
a useful hydrophilic matrixing agent in sustained drug
delivery devices.
In another study Okra gum was evaluated as a controlled-
release agent in modified release matrices, in comparison
with sodium carboxymethyl cellulose (NaCMC) and
hydroxypropylmethyl cellulose (HPMC), using paracetamol 40as a model drug . Okra gum matrices provided controlled-
release of paracetamol for more than 6 h and the release rates
followed time-independent kinetics. The release rates were
dependent on the concentration of the drug present in the
matrix. Okra gum compared favourably with NaCMC, and a
combination of Okra gum and NaCMC, or on further addition
of HPMC resulted in near zero order release of paracetamol
from the matrix tablet. The results indicate that Okra gum
matrices could be useful in the formulation of sustained-
release tablets for up to 6 h.
Guar gum:
Guar gum comes from the endosperm of the seed of the
legume plant Cyamopsis tetragonolobus. Guar gum is
prepared by first drying the pods in sunlight, then manually
Amelia et al.: Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
88Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
separating from the seeds. The gum is commercially extracted
from the seeds essentially by a mechanical process of
roasting, differential attrition, sieving and polishing. The
seeds are broken and the germ is separated from the
endosperm. Two halves of the endosperm are obtained from
each seed and are known as undehusked Guar Splits. Refined
guar splits are obtained when the fine layer of fibrous
material, which forms the husk, is removed and separated
from the endosperm halves by polishing. The refined Guar
Splits are then treated and finished into powders by a variety
of routes and processing techniques depending upon the end 41product desired .
Chemically, guar gum is a polysaccharide composed of the
sugars galactose and mannose. The backbone is a linear chain
of β 1,4-linked mannose residues to which galactose residues
are 1,6-linked at every second mannose, forming short side-
Fig. 1: Chemical structure of guar gum
42branches .
Guar gum is more soluble than locust bean gum and is a better
emulsifier as it has more galactose branch points. It degrades 43at extremes of pH and temperature (e.g. pH 3 at 50°C) . It
remains stable in solution over pH range 5-7. Strong acids
cause hydrolysis and loss of viscosity, and alkalies in strong
concentration also tend to reduce viscosity. It is insoluble in
most hydrocarbon solvents.
Guar gum is used and investigated as a thickener in cosmetics,
sauces, as an agent in ice cream that prevents ice crystals from
forming and as a fat substitute that adds the "mouth feel" of fat
and binder or as disintegrator in tablets.
Besides being used as a matrix former for sustained release
tablets guar gum has been investigated as a carrier for
indomethacin for colon-specific drug delivery using in vitro 44methods . Studies in pH 6.8 phosphate buffered saline (PBS)
containing rat caecal contents have demonstrated the
susceptibility of guar gum to the colonic bacterial enzyme
action with consequent drug release. The pre-treatment of rats
orally with 1 ml of 2% w/v aqueous dispersion of guar gum for
3 days induced enzymes specifically acting on guar gum
thereby increasing drug release. A further increase in drug
release was observed with rat caecal contents obtained after 7
days of pre-treatment. The presence of 4% w/v of caecal
contents obtained after 3 days and 7 days of enzyme induction
showed biphasic drug release curves. The results illustrate the
usefulness of guar gum as a potential carrier for colon-45specific drug delivery .
Locust bean gum:
Locust Bean Gum (LBG) (also known as Carob Gum) is
obtained form the refined endosperm of seeds from the carob
tree Ceretonia Siliqua L. It is an evergreen tree of the legume
family. Carob bean gum is obtained by removing and
processing the endosperm from seeds of the carob tree.
Processing of the ground endosperm is accomplished by
dispersing the fine powder in boiling water and filtering to
remove impurities. The gum is recovered by evaporating the 46solution and tray or roll drying .
Locust bean gum (LBG) is a plant seed galactomannan,
composed of a 1-4 linked β-D-mannan backbone with 1- 6-
Fig. 2: Chemical structure of locust bean gum
47linked α-D-galactose side groups . This neutral polymer is
only slightly soluble in cold water; it requires heat to achieve 48full hydration, solubilization and maximum viscosity .
The physico-chemical properties of galactomannan are 49strongly influenced by the galactose content .
A controlled delivery system for propranolol hydrochloride
(PPHCL) using the synergistic activity of LBG and xanthan
gum (X) was studied. Granules of PPHCL were prepared by
using different drug: gum ratios of X, LBG alone and a
mixture of XLBG (X and LBG in 1: 1 ratios). The XLBG
matrices exhibited precise controlled release than the X and
LBG matrices because of burst effect and fast release in case
of X and LBG alone respectively and there was no chemical
interaction between drug and polymers in the XLBG
formulation as conformed by FTIR studies. The first-pass 50effect of PPHCL can be avoided by using this formulation .
Amelia et al.: Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
89Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
Isapgulla husk (Psyllium):
Psyllium seed husks, also known as ispaghula, isabgol, or
simply as psyllium, are portions of the seeds of the plant
Plantago ovata, (genus plantago), a native of India and
Pakistan. Gel forming fraction of the alkali-extractable
polysaccharides is composed of arabinose, xylose and traces
of other sugars.
They are soluble in water, expanding and becoming
mucilaginous when wet. Seeds are used commercially for the
production of mucilage. It is white fibrous material,
hydrophilic in nature and forms a clear colorless
mucilaginous gel by absorbing water. Psyllium seed husk is 51used as binder, disintegrant and release retardant .
In an attempt, psyllium and acrylic acid based pH sensitive
novel hydrogels using N, N methylenebisacrylamide (N, 0
NMBAAm) as crosslinker and ammonium persulfate (APS)
as initiator for model drugs (tetracycline hydrochloride,
insulin and tyrosine), for the use in colon specific drug
delivery was studied. The hydrogel was evaluated for the
swelling mechanism and drug release mechanism from the
polymeric networks. The effects of pH on the swelling
kinetics and release pattern of drugs have been studied by
varying the pH of the release medium. It has been observed
that swelling and release of drugs from the hydrogels
occurred through non-Fickian or anomalous diffusion
mechanism in distilled water and pH 7.4 buffer. It shows that
the rate of polymer chain relaxation and the rate of drug 52diffusion from these hydrogels are comparable .
Sterculia foetida:
Sterculia is a genus colloquially termed as tropical chestnuts,
(Sterculia foetida). It contains a mixture of D-galactose, L-
rhamnose and D-galactouronic acid. The galctouronic acid 48units are the branching points of the molecule .
In an independent investigation Sterculia foetida gum as a
hydrophilic matrix polymer for controlled release preparation
was evaluated. Different formulation aspects considered
were: gum concentration (10–40%), particle size (75–420
µm) and type of fillers. Tablets prepared with Sterculia foetida
gum were compared with tablets prepared with Hydroxy
methyl cellulose K15M. The release rate profiles were
evaluated through different kinetic equations: zero-order,
first-order, Higuchi, Hixon-Crowell and Korsemeyer and
Peppas models. Suitable matrix release profile was obtained
at 40% gum concentration. Higher sustained release profiles
were obtained for Sterculia foetida gum particles in size range
of 76– 125 µm. The in vitro release profiles indicated that
tablets prepared from Sterculia foetida gum had higher
retarding capacity than tablets prepared with Hydroxy methyl 53cellulose K15M prepared tablets .
Honey locust gum:
It is known botanically as Gleditsia triacanthos, and belongs
to the order Leguminosea (suborder Mimoseae). The gum is
obtained from the seeds of the plant. The seed contains 54proteins, fats, carbohydrates and fibers .
Honey locust gum (HLG) was used to produce matrix tablets
at different concentrations (5% and 10%) by wet granulation 55method . Theophylline was chosen as a model drug. The
matrix tablets containing hydroxyethylcellulose and
hydroxypropyl methylcellulose as sustaining polymers at the
same concentrations were prepared and a commercial
sustained release (CSR) tablet containing 200 mg
theophylline was examined for HLG performance. No
significant difference in in-vitro studies was found between
CSR tablet and the matrix tablet containing 10% HLG.
Tara Gum:
Tara gum is obtained from the endosperm of seed of
Caesalpinia spinosa, commonly known as tara. It is small tree
of the family Leguminosae or Fabaceae. Tara gum is a white,
nearly odorless powder. It is produced by separating and 56grinding the endosperm of the mature black color seeds .
The major component of the gum is a galactomannan
polymer similar to the main components of guar and locust
bean gums, consist of a linear main chain of (1-4)-β-D-
mannopyranose units with α-D-galactopyranose units
attached by (1-6) linkages. The ratio of mannose to galactose
in tara gum is 3:1. produce highly viscous solutions, even at
1% concentration. Tara gum requires heating to disrupt
aggregation and full dissolution, whereas guar gum is soluble 57in cold water .
Tara gum is used as a thickening agent and stabilizer in a wide
range of food applications around the world. The use of tara
gum as a controlled release carrier in the formulation of gastro 58 59retentive controlled release tablets and emulsions for drugs
like metformin hydrochloride, ciprofloxacin hydrochloride
nimodipine, nifedipine, carvedilol, clozapine has been
claimed in patents.
Khaya gum:
Khaya gum is a polysaccharide obtained from the incised
trunk of the tree Khaya grandifoliola (family Meliaceae). It is
,
Amelia et al.: Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
90Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
known to contain highly branched polysaccharides consisting
of D galactose, L-rhamnose, D-galacturonic acid and 4-O-60methyl-D-glucoronic acid . Khaya gum has been shown to
be useful as a binding agent in tablet formulations. Khaya
gum is a hydrophilic polymer and has been shown to possess
emulsifying properties comparable with acacia gum. The fact
that the gum is naturally available, inexpensive and non-toxic
has also fostered the interest in developing the gum for
pharmaceutical use. Further work has also shown its potential
as a directly compressible matrix system in the formulation of 61controlled release tablets .
Khaya gum has been successfully evaluated as a controlled
r e l e a s e a g e n t i n c o m p a r i s o n w i t h
hydroxypropylmethylcellulose (HPMC) using paracetamol
(water soluble) and indomethacin (water insoluble) as model
drugs. Tablets were produced by direct compression and the
in-vitro drug release was assessed in conditions mimicking
the gastrointestinal system. Khaya gum matrices provided a
controlled release of paracetamol for up to 5 h. The release of
paracetamol from khaya gum matrices followed time-
independent kinetics and release rates were dependent on the
concentration of the drug present in the matrix. A combination
of khaya gum and HPMC gave zero-order time-independent 62release kinetics .
In another study Khaya and albizia gums were evaluated as
compression coatings for target drug delivery to the colon
using indomethacin and paracetamol as model drugs. The
core tablets were compression-coated with 300 and 400 mg of
khaya gum & albizia gum respectively and also a mixture of
khaya and albizia gum (1:1). Drug release studies indicated
that khaya and albizia gums were capable of protecting the
core tablet in the physiological environment of the stomach
and small intestine, with albizia gum showing greater ability
than khaya gum. The release from tablets coated with the
mixture of khaya and albizia gums was midway between the
two individual gums, indicating that there was no interaction
between the gums. Studies carried out using rat caecal matter
in phosphate-buffered saline at pH 6.8 (simulated colonic
fluid) showed that the gums were susceptible to degradation
by the colonic bacterial enzymes, leading to release of the
drug. The results demonstrate that khaya gum and albizia gum 61have potential for drug targeting to the colon .
Aloe Mucilage:
Many compounds with diverse structures
have been isolated from both the central parenchyma tissue of
Aloe mucilage is obtained from the leaves of Aloe
barbadensis Miller.
Aloe vera leaves and the exudate arising from the cells
adjacent to the vascular bundles. The bitter yellow exudate
contains 1,8 dihydroxyanthraquinone derivatives and their 63glycosides . The aloe parenchyma tissue or pulp has been
shown to contain proteins, lipids, amino acids, vitamins,
enzymes, inorganic compounds and small organic
compounds in addition to the different carbohydrates. Many
investigators have identified partially acetylated mannan (or
acemannan) as the primary polysaccharide of the gel, while
others found pectic substance as the primary polysaccharide.
Fig. 3: Chemical structure of acemannan
O t h e r p o l y s a c c h a r i d e s s u c h a s a r a b i n a n ,
arabinorhamnogalactan, galactan, galactogalacturan,
glucogalactomannan, galactoglucoarabinomannan and
glucuronic acid containing polysaccharides have been 64isolated from the Aloe vera inner leaf gel part .
A. vera has been used for many centuries for its curative and
therapeutic properties. In the pharmaceutical industry, it has
been used for the manufacture of topical products such as
ointments and gel preparations, as well as in the production of 65, 66tablets and capsules . Important pharmaceutical properties
that have been recently discovered for both the A. vera gel and
whole leaf extract include the ability to improve the
bioavailability of co-administered vitamins in human 67subjects .
Dried A. vera leaf gel (acetone precipitated component of the
pulp) was directly compressed in different ratios with a model
drug to form matrix type tablets, including ratios of 1:0.5, 1:1,
1:1.5 and 1:2. These matrix systems showed good swelling
properties that increased with an increase of aloe gel
concentration in the formulation. The directly compressed
matrix type tablets also showed modified release behavior
with 35.45% and 30.70% of the dose released during the first
hour and the remaining of the dose was released over a 6 hour
period for those formulations containing the lower ratios of
gel to drug, namely 1:0.5 and 1:1. The formulation that
contained the highest ratio of gel to drug, namely 1:2
exhibited only a 23.25% drug release during the first hour
with the remaining of the dose being released over an 8 hour
period. The dried A. vera gel polysaccharide component
therefore showed excellent potential to be used as an
excipient in the formulation of direct compressible sustained-68release matrix type tablets .
Amelia et al.: Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
91Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
Hakea Gum:
Hakea gum a dried exudate from the plant Hakea gibbosa
family Proteaceae. Gum exudates from species have been
shown to consist of L-arabinose and D-galactose linked as in
gums that are acidic arabinogalactans (type A). Molar
proportions (%) of sugar constituents Glucuronic acid,
Galactose, Arabinose, Mannose, Xylose is 12:43:32:5:8. The 69exuded gum is only partly soluble in water .
Hakea gibbosa (Hakea) was investigated as a sustained-
release and mucoadhesive component in buccal tablets.
Tablet with drug chlorpheniramine maleate (CPM) with
either sodium bicarbonate or tartaric acid in a 1:1.5 molar
ratio and different amount of Hakea were formulated using a
direct compression technique and were coated with
hydrogenated castor oil (Cutina) on all but one face. The
resulting plasma CPM concentration versus time profiles was
determined following buccal application of the tablets in
rabbits. The force of detachment for the mucoadhesive buccal
tablets increased as the amount of Hakea gum was increased
following application to excised intestinal mucosa. Addition
of sodium bicarbonate or tartaric acid, as well as higher
amounts of CPM, did not affect the mucoadhesive bond
strength. These results demonstrate that the novel, natural
gum, H. gibbosa, may not only be used to sustain the release 70but can also act as bioadhesive polymer .
Konjac glucomannan:
Konjac glucomannan, which is extracted from the tubers of
Amorphophallus konjac is a very promising polysaccharide
for incorporation into drug delivery systems. The konjac
glucomannan molecule consists of D-glucose and D-
mannose linked by 13-1,4 linkage, and the ratio of mannose to
glucose has been reported as 1.6:1, while there is some
It was shown that konjac glucomannan (KGM) gel systems
were able to maintain integrity and control the release of
theophylline and diltiazem for 8 hours. The Japanese and
European varieties of KGM synergistically interact with
Xanthan gum (XG) giving rise to gel formation; the
synergism being maximum at a 1:1 ratio. By contrast, the
American KGM does not show such effect forming only
viscous solutions. Drug diffusion coefficients of theophylline
and diltiazem HCl, with different molecular size and net
charge, were evaluated in systems containing KGM/XG in the
ratio of 1:1. KGM/XG systems were more efficient than the
XG alone for controlling drug diffusion of small molecules 72because of the gel formation .
Matrix tablets prepared from konjac glucomannan alone
showed the ability to sustain the release of cimetidine in the
physiological environments of the stomach and small
intestines but the presence of β mannanase (colon)
accelerated the drug release substantially. Mixtures of konjac
glucomannan and xanthan gum in matrix type tablets showed
high potential to sustain and control the release of the drug due
to stabilization of the gel phase of the tablets by a network of
intermolecular hydrogen bonds between the two polymers to 73effectively retard drug diffusion .
Mimosa scabrella:
Highly hydrophilic galactomannan is obtained from the seeds
of Mimosa scabrella (a brazilian leguminous tree called
bracatinga) of the Mimosaceae family. Its seeds provided
20–30% of galactomannan (G) with a mannose: galactose
ratio of 1.1:1. The galactomannan was obtained by first
milling the seeds of M. scabrella followed by boiling in water
for 10 min and then extracting from the aqueous phase for 4 h 0under mechanical stirring at 30 C. The dispersion was filtered
and the filtrate was precipitated with ethanol 50% (v/v). The
precipitate was washed in a gradient of ethanol (70–100% 74v/v) and dried .
In an independent study directly compressed theophylline
tablets, containing commercial xanthan (X) (Keltrol®) and a
highly hydrophilic galactomannan (G) from the seeds of
Mimosa scabrella as release-controlling agents, was studied.
Gums were used at 4, 8, 12.5 and 25% (w/w), either alone or in
mixture (X:G 1:1). The G obtained by different methods was
vacuum oven dried (VO) or spray dried (SD), which were
then evaluated for their in vitro drug release. The pH of the
dissolution medium (1.4) was changed to 4.0 and 6.8 after 2
and 3 h, respectively. Tablets containing G (SD) resulted in
more uniform drug release than G (VO) ones, due to their
Fig. 4: Chemical structure of konjac glucomannan
71branching at the C-3 of the mannose unit . Since konjac
glucomannan by itself forms very weak gels, it has been
investigated as an effective excipient in controlled release
drug delivery devices in combination with other polymers or
by modifying its chemical structure.
Amelia et al.: Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
92Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1
smaller particle size. As the polymer concentration was
increased the drug release decreased and all formulations at
25% w/w of gums showed excessive sustained release effect.
The matrices made with alone X showed higher drug
retention for all concentrations, compared with G matrices
that released the drug too fast. The XG matrices were able to
produce near zero-order drug release. The XG (SD) 8% of
tablets provided the required release rate (about 90% at the 74end of 8 h), with zero-order release kinetics .
Mimosa pudica:
Mimosa pudica, commonly known as sensitive plant belongs
to family Mimosaceae. Mucilage of M. pudica is obtained
from seeds, which is composed of d-xylose and d-glucuronic
acid. Mimosa seed mucilage hydrates and swells rapidly on
coming in contact with water. Earlier the seed mucilage was 75evaluated for binding and disintegrating agent .
In a study of mucilage obtained from M. pudica as sustained
release material was investigated. Matrix tablets containing
different proportions of mucilage, dibasic calcium phosphate
as diluent and diclofenac sodium as model drug was
formulated by wet granulation method. The study reveals that
the drug release from the matrix tablet decreases as the
concentration of mucilage increased and followed Higuchi
square root release kinetics. The drug release mechanism was
mainly diffusion for tablets containing higher proportion of
mucilage and a combination of matrix erosion and diffusion
for tablets containing smaller proportion of mucilage. The
study demonstrated that formulation containing mucilage to
drug in the proportion of 1:40 was found to be similar to the 75commercial sustained-release formulation of diclofenac .
Hupu gum :
Hupu gum or Gum kondagogu (GKG) is a naturally occurring
polysaccharide derived as an exudate from the tree
(Cochlospermum gossypium). Basically it is a polymer of
Fig. 5
rhamnose, galacturonic acid, glucuronic acid, b-D
galactopyranose, a-D-glucose, b-D-glucose, galactose,
arabinose, mannose and fructose with sugar linkage of (12) b-
D-Gal p, (16), b-D-Gal p, (14) b-D-Glc p, 4-0-Me-a-D-Glc p, 76,77(12) a-L-Rha . Hupu gum is also composed of higher
78uronic acid content, protein, tannin and soluble fibers .
Gastric floating drug delivery system of Diltiazem HCl was
studied using hupu gum as matrix forming polymer. Tablets
were prepared by wet granulation method. Optimization
study was carrier by three factor, three level Box-Behnken
Design. The polymer concentration, % w/w of sodium
bicarbonate and % w/w of pharmatose to the weight of drug
and polymer were selected as independent variables.
Cumulative percent drug released at 12 hrs was selected as
dependent variable. The release rate decreased as the
proportion of hupu gum increased. The results demonstrated
that hupu gum is a suitable polymer for sustained release 79gastric floating system .
Albizia gum:
Albizia gum is obtained from the incised trunk of the tree
Albizia zygia, family Leguminosae and is shaped like round
elongated tears of variable color ranging from yellow to dark
brown. It consists of β-1– 3-linked D-galactose units with
some ß1-6-linked D-galactose units. The genus Albizzia
containing some twenty-six species is a member of the
Mimosaceae, a family which also includes the gum-bearing
genera Acacia and Prosopis. Only two species of Albizia, A.
zygia and A. sassa, are however, known to produce gum.
Albizia gum has been investigated as a possible substitute for
gum arabic as a natural emulsifier for food and 80,81pharmaceuticals . These gums were tried as coating
materials in compression-coated tablets, which degraded, by 62the colonic microflora, thereby releasing the drug .
Fenugreek:
Trigonella Foenum-graceum, commonly known as
Fenugreek, is an herbaceous plant of the leguminous family.
Fenugreek seeds contain a high percentage of mucilage (a
natural gummy substance present in the coatings of many
seeds). Although it does not dissolve in water, mucilage forms
a viscous tacky mass when exposed to fluids. Like other
mucilage- containing substances, fenugreek seeds swell up 82and become slick when they are exposed to fluids .
The husk from the seeds is isolated by first reducing the size,
then separated by suspending the size reduced seeds in
chloroform for some time and then decanting. Successive
extraction with chloroform removes the oily portion which is 83then air dried .
A different extraction procedure is also reported to isolate the
mucilage from the husk. The powdered seeds are extracted
with hexane then boiled in ethanol. The treated powder is then
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soaked in water and mechanically stirred and filtered. Filtrate
is then centrifuged, concentrated in vacuum and mixed with
96% ethanol. This is then stored in refrigerator for 4 hrs to 84precipitate the mucilage .
The mucilage derived from the seeds of fenugreek, was
investigated for use in matrix formulations containing
propranolol hydrochloride. Methocel® K4M was used as a
standard controlled release polymer for comparison purposes.
A reduction in the release rate of propranolol hydrochloride
was observed with increase in concentration of the mucilage
in comparison to that observed with hypomellose matrices.
The rate of release of propranolol hydrochloride from
fenugreek mucilage matrices was mainly controlled by the
drug: mucilage ratio. Fenugreek mucilage at a concentration
of about 66% w/w was found to be a better release retardant 84compared to hypomellose at equivalent content .
Lepidium sativum:
In a different study a gel forming husk powder obtained from
Lepidium sativum seeds was used to prepare solid controlled
release oral unit dose pharmaceutical composition,
comprising one or more of therapeutic agent/drug. The gel
forming husk powder obtained from Lepidium stivum seeds
is present in the range of 10 to 70 % of the total weight of
dosage form, the cross-linking enhancer selected from
xanthan gum, karaya gum and the like in amounts of between
3 to 10 % by weight of the dosage form to give a release profile
between 4 to 20 hours. The total excipients present are 85between 10 to 40 % by weight of the total dosage form .
RESINS:
Gum Copal:
Gum copal (GC) is a natural resinous material of plant
Bursera bipinnata (family Burseraceae).Copal, a resinous
material, is obtained from the plants of araucariaceae and 86caesalpinaceae, a subfamily of leguminoaceae .
Copal resin (CR) contains agathic acid, a diterpenoid and
related lobdane compounds along with cis-communic acid,
trans-communic acid, polycommunic acid, sandaracopimaric
acid, agathalic acid, monomethyl ester of agathalic acid,
agatholic acid and acetoxy agatholic acid. CR obtained from
leguminoaceae family contains copalic acid, pimaric acid,
i sopimaric acid , dehydro-dehydroabie t ic acid , 86dehydroabietic acid and abietic acid .
Medicinally, Copal is used in the treatment of headache, 87fever, burns and stomach ache . In dentistry, it is used as
binding media in dental products and in treatment of micro
88leakage in teeth . Recently, Copal gum has been evaluated as 13matrix-forming material for sustaining the drug delivery .
In an independent study copal resin was investigated as a film 89forming agent . The free films, prepared in alcohol by
solvent evaporation technique, were brittle with high tacking
property. Addition of 1% w/w propylene glycol improved the
mechanical properties of copal resin films, whereas glyceryl
monostearate, sorbitan mono-oleate and sorbitan
monolaurate in 15% w/w reduced the tackiness significantly.
CR films showed good swelling property in phosphate buffer
(pH 7.4). It was concluded that it can be used as a coating
material for sustained release and colon-targeted drug
delivery.
Gum Damar:
Gum damar (GD) is a whitish to yellowish natural gum of
plant Shorea wiesneri (family Dipterocarpaceae). It contains
about 40% alpha-resin (resin that dissolves in alcohol), 22% 13beta resin, 23% dammarol acid and 2.5% water .
It has been used for water-resistant coating and in
pharmaceutical and dental industries for its strong binding 90properties . In India, Sal damar has been widely utilized in
91the indigenous system of medicine .
Natural gum copal and gum damar as novel sustained release
matrix forming materials in tablet formulation was evaluated.
Matrix tablets were prepared by wet granulation technique
using isopropyl alcohol as a granulating agent. Diclofenac
sodium was used as a model drug. Effect of gum
concentration (10, 20 and 30% w/w with respect to total tablet
weight) on in vitro drug release profile was examined. Matrix
tablets with 30% w/w gum copal and gum damar showed
sustained drug delivery beyond 10 h. Drug release from gum
copal matrix tablets followed zero order kinetics while gum
damar (10 and 20% w/w) was found suitable to formulate the
insoluble plastic matrix that releases the drug by diffusion. It
was concluded that both gums possess substantial matrix
forming property that could be used for sustained drug 13delivery .
TANNINS:
Bhara Gum:
Gum Bhara is a yellowish natural gum of plant Terminalia
bellerica roxb. belonging to family Combretaceae. Bahera
gum, extracted from the bark of Terminalia bellerica, is a 92waste material . Main chemical constitutents are tannins
which mainly include ß- sitosterol, gallic acid, ellagic acid, 93ethyl gallate, galloyl glucose and chebulaginic acid .
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It has been mainly used as a demulcent and purgative. It is
also used as an emulgent in cosmetic industries. Wide
applications of bhara gum indicate their hydrophilic nature, 94and compatibility with the physiologic environment .
A new sustained release microencapsulated drug delivery 95system employing bhara gum has been proposed . The
microcapsules were formulated by ionic gelation technique
using famotidine as the model drug. The effect of different
drug: bhara gum ratio on in vitro drug release profile was
examined and compared with guar gum. Remaining all
parameters was constant. Microcapsules employing bhara
gum exhibited slow release of famotidine over 10 hr. Fickian
release was observed from most of the formulations with
bhara gum. It was concluded that this gum possesses
substantial release controlling properties that could be used
for sustained drug delivery.
OTHERS:
Moi gum:
The gum is obtained from Lannea coromandelica (Houtt.)
Merrill (Anacardiaceae). Moi gum is yellowish white color in
fresh and on drying becomes dark. Gum ducts are present in leaves, stems and fruits and are most abundant in the bark of
96the stem .
Natural gum moi was successfully evaluated as
microencapsulating agent and release rate controlling
material for lamivudine. Microspheres were prepared by
solvent evaporation technique. Effect of drug: gum ratio on in
vitro drug release profile was investigated. The rate limiting
capacity of moi gum was compared with guar gum as control
by keeping all the parameters constant. The gum produced
microspheres having satisfactory size (24-32µm) and
acceptable morphological properties. Microspheres of moi
gum exhibited sustained action beyond 10 hr in comparison to
guar gum but the combination of both the gums in 1:1 ratio 98demonstrated an additional sustained action .
CONCLUSION
The use of natural gums for pharmaceutical applications is
attractive because they are economical, readily available,
non-toxic, capable of chemical modifications, potentially
The roots contain cluytyl ferulate; heartwood gives
lanosterol; bark, dlepi- catechin and (+)-leucocyanidin;
flowers and leaves, ellagic acid, quercetin and quercetin-3
arabinoside. Flowers also contain iso-quercetin and morin.
Leaves in addition contain beta-sitosterol, leucocyanidin and 97leucodelphinidin .
biodegradable and with few exceptions, also biocompatible.
Majority of investigations on natural polymers in drug
delivery systems center around polysaccharides. Natural
gums can also be modified to have tailor-made products for
drug delivery systems and thus can compete with the
synthetic controlled release excipients available in the
market. Though the use of traditional gums has continued,
newer gums have been used, some of them with exceptional
qualities. Many other new gums viz. sesbenia gum, tara gum,
etc. can be explored for their sustained release properties.
These have found application not only in sustaining the
release of the drugs but are also proving useful for
development of gastro retentive dosage form, bioadhesive
system, microcapsules etc.
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