Plant Based Natural Gums in NDDS

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



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 .



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

,



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 .



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.



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



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 .



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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Plant Based Natural Gums in NDDS

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