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PLANT DERIVED NATURAL GUMS AND POLYMERS FOR DRUG DELIVERY SYSTEM Report Submitted to Tamilnadu State Council for Higher Education Under Minor Research Project scheme for teachers D.O.Rc. No.1418/2014A dt 02.03.2015. By Dr.T.S.Subha Head and Associate Professor, PG Department of Botany, Bharathi Women’s College (Autonomous) Chennai 600 108.

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Page 1: Dr.T.S - tnuniv.ac.in PDF13-2014-15/11- Dr. T.S. Subha.pdf · Chennai 600 108. 1 ... Biopolymers used in film preparation are often carbohydrates or proteins extracted or separated

PLANT DERIVED NATURAL GUMS AND POLYMERS FOR

DRUG DELIVERY SYSTEM

Report Submitted to

Tamilnadu State Council for Higher Education

Under

Minor Research Project scheme for teachers

D.O.Rc. No.1418/2014A dt 02.03.2015.

By

Dr.T.S.Subha

Head and Associate Professor,

PG Department of Botany,

Bharathi Women’s College (Autonomous)

Chennai 600 108.

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INTRODUCTION

Polymers have been successfully employed in formulation of solid, liquid and semi-solid forms

for drug delivery systems. Both synthetic and natural polymers have been investigated extensively

for this purpose; however qualities like being economical, readily available, non-toxic, capable of

chemical modifications, biodegradable and mostly biocompatible makes natural polymers more

preferred. Excipients included in drug formulations serve as inert vehicles that provide necessary

weight, consistency, volume, stability, helps in release and increases the bioavailability of active

ingredients and also enhancement of patient acceptability. The specific application of plant-

derived polymers in pharmaceutical formulations include their use in the manufacture of solid

monolithic matrix systems, implants, films, beads, micro &nanoparticles, inhalable and injectable

systems as well as viscous liquid formulations. The use of plant-derived polymers as excipients in

the formulation of drug delivery systems is given below:

Cellulose: Cellulose is an essential structural component of cell walls in higher plants, it is an

unbranched polysaccharide consisting of β-1,4-linked D glucose units, used in pharmaceutical

applications such as a filler in tablets.

Hemicellulose: Hemicellulose consists of xyloglucans, xylans and mannans extracted from plant

cell wall with a strong alkali. Their backbones are made up of β-1,4-linked D-glycans.

Pectin: Pectin is a family of complex polysaccharides present in the walls of plant cells.. The main

component of pectin is a linear polysaccharide composed of α-1,4-linked D-galacturonic acid

units, but the linear structure is interrupted with highly branched regions.

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Inulin: Inulin consists of a mixture of oligomers and polymers that belong to the group of gluco-

fructans and occur in plants such as garlic, onion, artichoke and chicory. The inulin molecules

contain two to more than 60 fructose molecules linked by β-2,1-bonds.

Alginates: Alginates are linear, unbranched polysaccharides found in brown seaweed such as

Laminaria hyperborea,Ascophyllum nodosum and Macrocystis pyrifera. These polymers consist

of two different monomers in varying proportions, namely β-D-mannuronic acid and α-L-

guluronic acid linked in α- or β-1,4glycosidic bonds.

Carrageenans: Carrageenans is the generic name for a family of high molecular weight sulphated

polysaccharides obtained from red seaweeds belonging to the class Rhodophyceae, especially

Chondrus crispus, Euchema spp, Gigartina stellata and Iridaea spp.

Rosin: Rosin is a natural polymer with a low molecular weight of 400 Da obtained from the

oleoresin of pine trees, such as Pinus soxburghui, Pinus longifolium and Pinus toeda. Rosin is

primarily composed of abietic and pimaric acids and has excellent film-forming properties. Rosin

and its derivatives are biopolymers that are used for their pharmaceutical applications.

GUMS AND MUCILAGES

Natural gums (gums obtained from plants) are hydrophilic carbohydrate polymers of high

molecular weights, are either water soluble or absorb water and swell up or disperse in cold water

to give a viscous solution or jelly. Gums are widely used natural excipients for conventional and

novel dosage forms. Mucilages are slimy aqueous dispersions produced by plants, animals and

microbes, which consist basically of water soluble polysaccharides including starches and

modified starches. Gums and Mucilage can be modified in different ways to obtain tailor made

materials for drug-delivery systems and thus can compete with synthetic excipients.

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Few gums and mucilage are already explored as various drug delivery systems to mention a few:

Guar gum : Guar gum is also called as guaran, Gum cyamposis, Guarina, Glucotard and

Guyarem. Guar gum is a galactomannan, which is a storage polysaccharide in seed endosperm of

plants in the Fabaceae family. Galactomannans are linear polysaccharides consisting of (1→4)-

diequatorially linked β-D-mannose monomers, some of which are linked to single sugar side-

chains of α-D-galactose attached.

Locust bean gum: Locust bean gum also known as Carob bean gum is derived from the seeds of

the leguminous plant Ceratonia siliqua Linn. Locust bean gum consists mainly of a neutral

galactomannan polymer made up of 1,4-linked D-mannopyranosyl units and every fourth or fifth

chain unit is substituted on C6 with a D-galactopyranosyl unit. Locust bean gum is a neutral

polymer and its viscosity and solubility are therefore little affected by pH changes within the range

of 3-11.

Gum Arabic : Gum arabic is a natural polysaccharide which is obtained from the exudates of

Acacia trees. Structurally, gum arabic is a branched molecule with the main chain consisting of

1,3-linked β-D galactopyranosyl units with other carbohydrates such as arabinose, glucuronic acid

and rhamnose. Gum arabic was successfully used as a matrix microencapsulating agent for the

enzyme, endoglucanase, which proofed to give slow release of the encapsulated enzyme .

Psyllium: Psyllium mucilage is obtained from the seed coat of Plantago ovata by milling the outer

layer of the seeds. It has been evaluated for its tablet binding properties, but also to form hydrogels

through radiation-induced cross-linking for controlled release of 5-fluorouracil as model drug.

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Starch: Starch is a storage carbohydrate comprised of two polymers namely amylose (a non-

branching helical polymer consisting of α-1,4 linked D-glucose monomers) and amylopectin (a

highly branched polymer consisting of both α-1,4 and α-1,6 linked D-glucose monomers).

Aloe gel: The inner part of the leaves of Aloe vera (L.) Burm.f. (Aloe barbadensis Miller) consists

of the parenchyma tissue that contains the mucilaginous gel.

There are many unexplored or under explored gums and mucilage which has pharmaceutical

applications such as being used as Hydrogels and biopolymer films or membrane.

Hydrogels:

Hydrophilic gels are usually referred to as hydrogels are networks of polymer chains that are

sometimes found as colloidal gels in which water is the dispersion medium. In general hydrogel is

a water-swollen, and cross-linked polymeric network produced by the simple reaction of one or

more monomers. They possess degree of flexibility very similar to natural tissue due to their large

water content.

Biopolymer Film:

Biopolymers used in film preparation are often carbohydrates or proteins extracted or separated

from plants, animal tissues or animal products. The storage carbohydrate in plants is starch.

Depending on the plant the starch is formed in different parts of the plant, e.g., grain, tuber or root

(Banks and Greenwood, 1975). Other carbohydrates found in the plants e.g. the cell wall include

cellulose and pectin (MacDougall and Ring, 2004). Some carbohydrates, such as alginate and

carrageenan, are found in seaweeds (Ramsden, 2004). Cereal grains contain, in addition to starch,

protein, such as gluten (wheat) and zein (maize) (Bergthaller, 2004). Biopolymers extracted from

animal products or parts are also used in edible film manufacturing. Casein and whey proteins are

separated from milk and they are often used to prepare films (McHugh and Krochta, 1994a).

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OBJECTIVES

The major objectives of proposed study are

� Identification of plant material for production of gums and polymers.

� Screening for plants that are either less or not exploited for production of gum and polymers

across Tamil nadu.

� Isolation and purification of the Gum.

� Physical, chemical and biological characterization and standardization of gums and mucilage.

� Preparation of biomaterials such as Hydrogels, Sheets etc.

� Drug release studies

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REVIEW OF LITERATURE

A polymer is a large molecule (macromolecules) composed of repeating structural units typically

connected by covalent chemical bonds. Polymers have been in use for many years with the aim of

facilitating the effectiveness and efficiency of drugs and their delivery. Biodegradable polymers

are widely being studied as a potential carrier material for site specific drug delivery because of

their non-toxic, biocompatible nature. Natural polysaccharides have been investigated for

application in drug delivery industry as well as in biomedical fields. Modified polymer has found

its application as a support material for gene delivery, cell culture, and tissue engineering.

Nowadays, polymers are being modified to obtain novel biomaterials for controlled drug delivery

applications.

Natural polymers have emerged as one of the most widely researched materials for enhancing the

therapeutic effects of the existing drug molecules. Natural polymers are biodegradable,

biocompatible and relatively safer when compared to synthetic resources. Various sources of

natural polymers include plants, animals and microbes like bacteria and fungi. Carbohydrates have

been widely used in various forms. Carbohydrate polymers are being extensively studied for

biomedical and pharmaceutical applications. Polysaccharides like starch, pectin, guar gum etc are

used for the preparation of different types of dosage forms of drugs. Controlled release

preparations of isoniazid and diltiazem have been prepared with the help of guar gum.

The film forming ability of gums recognized recently has helped in actualizing the concepts and

products like breath films, cough strips and sore throat strips. Similarly, xyloglucan and borax –

gaur gum have influenced the colon specific drug delivery formulations. Xanthan gum,

polysaccharide is extracted from microbe. It is a highly branched glucamannan and has shown

consistency in its properties over a wide pH range which in turn has its application in food,

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pharmaceutical and cosmetic formulations. It is found in number of drug preparations including

cefdinir oral suspension and nitazoxanide tablets.

Natural polymers and their role in drug delivery:

These polymers may be of either plant origin, animal origin, marine origin or microbial origin

(fungi & bacteria). The following natural polymers are being extensively studied for their role as

a facilitator in drug delivery systems.

Cellulose: Microcrystalline cellulose is mainly used in the pharmaceutical industry as a

diluent/binder in tablets for both the granulation and direct compression processes. Controlled

release applications for cellulose derivatives include the formulation of membrane controlled drug

release systems or monolithic matrix systems. Film coating techniques for the manufacture of

membrane controlled release systems include enteric coated dosage forms and the use of

semipermeable membranes in osmotic pump delivery systems.

Hydroxypropylmethylcellulose is a partly Omethylated and O-(2-hydroxypropylated) cellulose

ether derivative that has been extensively investigated as an excipient in controlled release drug

delivery systems due to its gel forming ability. In a study where two cellulose ethers;

hydroxypropylmethylcellulose and carboxymethylcellulose were employed as polymeric carrier

materials in matrix tablets for controlling the release of a soluble drug, diltiazem, it was found that

each polymer on its own could sustain drug release over an extended period of time in these

systems. More importantly, a mixture of the two cellulose ethers in the matrix type tablets enabled

zero order drug release kinetics at both pH 4.5 and 6.8.15 Hydroxypropylmethylcellulose

monolithic matrix systems showed similar dissolution profiles as a commercial osmotic pump

system for glipizide, a drug with low solubility. It was further found that the

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hydroxypropylmethylcellulose matrix systems have a stronger gel structure than those made of

polyethylene oxide, which may provide superior in vivo performance in terms of matrix resistance

to the destructive forces within the gastrointestinal tract

Hemicellulose : A hemicellulose is a heteropolymer (matrix polysaccharides), such as

arabinoxylans, present along with cellulose in almost all plant cell walls. While cellulose is

crystalline, strong, and resistant to hydrolysis, hemicellulose has a random, amorphous structure

with little strength. Unlike cellulose, hemicellulose (also a polysaccharide) consists of shorter

chains - 500-3,000 sugar units. In addition, hemicellulose is a branched polymer, while cellulose

is unbranched. Hemicellulose polysaccharides consist of xyloglucans, xylans and mannans that

can be extracted from the plant cell wall with a strong alkali. They have backbones made up of ß-

1,4-linked Dglycans. Xyloglucan has a similar backbone as cellulose, but contains xylose branches

on 3 out of every 4 glucose monomers. The ß-1,4-linked DXylan backbone of arabinoxylan

contains arabinose branches.12, 13

Glucomannan: Glucomannan is a hydrocolloidal polysaccharide of the mannan family consisting

of ß-1,4 linked Dmannose and D-glucose monomers (with acetyl sidebranches on some of the

backbone units), but the mannose:glucose ratio may differ depending on the source. The acetyl

groups contribute to its solubility and swelling capacity and assist in making it a soluble natural

polysaccharide with the highest viscosity and water-holding capacity. It is very abundant in Nature

and this polysaccharide is specifically derived from softwoods, roots, tubers and plant bulbs. The

most commonly used type of Glucomannan is referred to as konjac Glucomannan, which is

extracted from the tubers of Amorphophallus konjac and is a very promising polysaccharide for

incorporation into drug delivery systems. Since konjac Glucomannan by itself forms very weak

gels, it has been investigated as an effective exponent in controlled release drug delivery devices

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in combination with other polymers or by modifying its chemical structure.17, 18 It was shown

that konjac Glucomannan gel systems were able to maintain the integrity and control the release

of theophylline and diltiazem for 8 hours. 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 ß-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 effectively

retard drug diffusion.19 Konjac Glucomannan was used to form hydrophilic cylinders and particles

for controlled release of DNA.20 Konjac Glucomannan cross-linked with trisodium

trimetaphosphate formed hydrogel systems that could sustain hydrocortisone release dependent on

crosslinking density and enzymatic degradation.

Agar :Agar or agar-agar is the dried gelatinous substance obtained from Gelidium amansii

(Gelidaceae) and several other species of red algae like, grailaria (Gracilariaceae) and Pterocladia

(Gelidaceae). Agar consists of a mixture of agarose and agaropectin. The predominant component,

agarose, is a linear polymer, made up of the repeating monomeric unit of agarobiose. Agarobiose

is a disaccharide made up of D-galactose and 3,6- anhydro-L-galactopyranose. Agaropectin is a

heterogeneous mixture of smaller acidic molecules that gel poorly. Its great gelling power in an

aqueous environment allows it to form gels which are more resistant (stronger) than those of any

other gelforming agent, assuming the use of equal concentrations. It can be used over a wide range

of pH, from 5 to 8, and in some cases beyond these limits. It withstands thermal treatments very

well, even above 100°C which allows good sterilization. A 1.5% aqueous solution gels between

32°C-43°C and does not melt below 85°C. This is a unique property of agar, compared to other

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gelling agents. Agar is used as Suspending agent, emulsifying agent, gelling agent in suppositories,

surgical lubricant, tablet disintegrants, medium for bacterial culture, laxative.

Starches: Starch or amylum is a carbohydrate consisting of a large number of glucose units joined

together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy

store. It is the principal form of carbohydrate reserve in green plants and especially present in seeds

and underground organs. Starch occurs in the form of granules (starch grains). A number of

starches are recognized for pharmaceutical use. These include maize (Zea mays), rice (Oryza

sativa), wheat (Triticum aestivum), and potato (Solanum tuberosum). It is comprised of two

polymers, namely amylose and amylopectin .

Modified Starch: It was tested for general applicability of a new pregelatinized starch product in

directly compressible controlled-release matrix systems. It was prepared by enzymatic degradation

of potato starch followed by precipitation (retrogradation), filtration and washing with ethanol.

The advantages of the material include ease of tablet preparation,

Native Starch: It may not be suitable in controlled release drug delivery systems due to substantial

swelling and rapid enzymatic degradation resulting in too fast release of many drugs. This has led

to the use of derivatives of starch that are more resistant to enzymatic degradation as well as

crosslinking and formation of co-polymers.

Pectin :Pectin is the purified carbohydrate product obtained by acid hydrolysis from the inner

portion of the rind of citrus peels i.e. Citrus Simon or Citrus Aurantium,(Rutaceae). The main

component of pectin is a linear polysaccharide composed of a-1,4-linked Dgalacturonic acid

residues interrupted by 1,2- linked L-rhamnose residues with a few hundred to about one thousand

building blocks per molecule, corresponding to an average molecular weight of about 50,000 to

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about 1,80,000. 28 The galacturonic acid polysaccharides are rich in neutral sugars such as

rhamnose, arabinose, galactose, xylose and glucose. The composition of pectin can vary based on

the botanical source, for example pectin from citrus contains less neutral sugars and has a smaller

molecular size as compared to pectin obtained from apples. 29, 30 Pectin has been investigated as

an excipient in many different types of dosage forms such as film coating of colon-specific drug

delivery systems . Calcium pectinate nanoparticles to deliver insulin were prepared as a potential

colonic delivery system by ionotropic gelation.32 Micro particulate polymeric delivery systems

have been suggested as a possible approach to improve the low bioavailability characteristics

shown by standard ophthalmic vehicles (collyria). In this context pectin microspheres of piroxicam

were prepared by the spray drying technique. In vivo tests in rabbits with dispersions of piroxicam-

loaded microspheres also indicated a significant improvement of piroxicam bioavailability in the

aqueous humour (2.5-fold) when compared with commercial piroxicam eye drops.33

Inulin:It is a polysaccharide from the bulbs of Dehlia, Inula Helenium (Compositae), roots of

Dendelion, Taraxacum officinale (Compositae). Burdock root, Saussurea lappa (Compositae) or

chicory roots, Cichonium intybus (Compositae).22 Inulin consists of a mixture of oligomers and

polymers that belong to the group of gluco-fructans and occur in plants such as garlic, onion,

artichoke and chicory. The inulin molecules contain from two to more than 60 fructose molecules

linked by ß-2,1- bonds. Inulin is resistant to digestion in the upper gastrointestinal tract, but is

degraded by colonic microflora.38, 39.41

Rosin:Rosin, also called colophony or Greek pitch (Pix græca), is a solid form of resin obtained

from pines and some other plants, mostly conifers, produced by heating fresh liquid resin to

vaporize the volatile liquid terpene components. Rosin is a natural polymer with a low molecular

weight of 400 Da obtained from the oleoresin of pine trees, with the principle sources being Pinus

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soxburghui, Pinus longifolium and Pinus toed a. Rosin is primarily composed of abietic and

pimaric acids and has excellent film-forming properties. Rosin and its derivatives are biopolymers

that are increasingly used for their pharmaceutical applications. In the pharmaceutical context it

has been investigated for microencapsulation, film-forming and coating properties, matrix

materials in the tablets for sustained and controlled release.1 Derivatives of rosin synthesized by a

reaction with polyethylene glycol 200 and maleic anhydride proofed suitable for sustaining the

drug release from matrix tablets and pellets.42 Polymerized rosin films containing hydrophobic

plasticizers showed excellent potential as coating materials for the preparation of sustained release

dosage forms. 43 Different studies on the film forming and coating properties of rosin and the

glycerol ester of maleic rosin demonstrated their potential to be used as coating materials for

pharmaceutical products as well as in sustained release drug delivery systems. It was shown that

hydrocortisone loaded nanoparticles prepared from rosin could slowly release this model drug,

which was dependent on the rosin content. This in vitro study demonstrated the potential of rosin

for the production of effective nanoparticulate drug delivery systems.

Alginates: Alginates or alginic acids is an anionic polysaccharide are linear,

unbranchedpolysaccharides found in brown seaweed and marine algae such as Laminaria

hyperborea, Ascophyllum nodosum and Macrocystis pyrifera. Alginic acid can be converted into

its salts, of which sodium alginate is the major form currently used. These polymers consist of two

different monomers in varying proportions, namely ß-D-mannuronic acid and a-L-guluronic acid

linked in a- or ß-1,4 glycosidic bonds as blocks of only ß-D-mannuronic acid or a-L-guluronic acid

in homopolymers or alternating the two in heteropolymeric blocks. Alginates have high molecular

weights of 20 to 600 kDa.12, 73 Alginates have been used and investigated as stabilizers in

emulsions, suspending agents, tablet binders and tablet disintegrants.47 The in vivo delivery of

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anti-tuberculosis drugs were investigated in mice for alginate nanoparticles prepared by cation

induced gelation. Bioadhesive sodium alginate microspheres of metoprolol tartrate for intranasal

systemic delivery were prepared to avoid the first-pass effect, as an alternative therapy for

injection, and to obtainimproved therapeutic efficacy in the treatment of hypertension and angina

pectoris.

Carrageenans: Carrageenan is sulphated polysaccharide extract of the seaweed called carrageen;

or Irish moss, the red algae obtained from Chondrus Crispus (Rhodophyceae). 22 Carrageenan

extracted from seaweed is not assimilated by the human body and provides only bulk but no

nutrition. There are three basic types of carrageenan - kappa (.), iota (.) and lambda (.)

respectively.12 The .-type carrageenan results in viscous solutions but are non-gelling, while the

.- type carrageenan forms a brittle gel.Hydrogel beads were prepared from a mixture of cross-

linked .-carrageenan with potassium and crosslinked alginate with calcium and they exhibited a

smoother surface morphology than that of the onepolysaccharide network beads. The carrageenan

parts of the hydrogen pronouncedly enhanced the thermostability of the polymeric network. These

beads were introduced as novel carriers for controlled drug delivery systems.78

Alginates: Alginate is a water soluble linear polysaccharide extracted from brown seaweed and is

composed of alternating blocks of 1-4 linked α–l-guluronic and α-D-mannuronic acid residues.

They are abundant in nature and are found as structural components of marinebrown algae and as

capsular polysaccharides in some soil bacteria. Commercial alginates are extracted from three

species of brown algae. These include Laminaria hyperborean, Ascophyllumnodosum, and

Macrocystispyrifera in which alginate comprises up to 40% of the dry weight. Bacterial alginates

have also been isolated from Azotobactervinelandii and several Pseudomonas species Alginates

are naturally derived polysaccharide block copolymers composed of regions of sequential β-D-

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mannuronic acid monomers (M-blocks), regions of α-L-guluronic acid (G blocks), and regions of

interspersed M and G units. The length of the M- and G-blocks and sequential distribution along

the polymer chain varies depending on the source of the alginate.Alginate-based materials are pH-

sensitive. Biomolecules release from alginate-based materials in low pH solutions is significantly

reduced which could be advantageous in the development of a delivery system.

Gums and Mucilages:

Guar Gum : Guar gum is the powder of the endosperm of the seeds of Cyamopsis tetragonolobus

Linn. (Leguminosae). 22 Guar gum is also called guaran, clusterbean, Calcutta lucern, Gum

cyamposis, Cyamopsis gum, Guarina, Glucotard and Guyarem. It is a galactomannans which is a

linear polysaccharide consisting of (1.4)-diequatorially linked ß-Dmannose monomers, some of

which are linked to single sugar side-chains of a-D-galactose attached. 45Guar gum has a backbone

composed of ß-1,4 linked- D-mannopyranoses to which, on average, every alternate mannose an

a-D-galactose is linked 1.6. 46 The FDA has affirmed guar gum as generally safe.47 Guar gum

has recently been highlighted as an inexpensive and flexible carrier for oral extended release drug

delivery.48 Guar gum is particularly useful for colon delivery because it can be degraded by

specific enzymes in this region of the gastrointestinal tract. The gum protects the drug while in the

stomach and small intestine environment and delivers the drug to the colon where it undergoes

assimilation by specific microorganisms or degraded by the enzymes excreted by these

microorganisms. Guar gum on its own showed high potential to serve as a carrier for oral

controlled release matrix systems.

Locust Bean Gum : Locust bean gum also known as Carob bean gum is derived from the seeds of

the leguminous plant Ceratonia siliqua Linn (Leguminosae). The brown pods or beans of the locust

bean tree are processed by milling the endosperms to form locust bean gum and it is therefore not

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an extract of the native plant but flour. Locust bean gum consists mainly of a neutral

galactomannan polymer made up of 1,4-linked Dmannopyranosyl units and every fourth or fifth

chain unit is substituted on C6 with a D-galactopyranosyl unit. Locust bean gum is a neutral

polymer and its viscosity and solubility are therefore little affected by pH changes within the range

of 3-11.53

Gum Arabic :Gum acacia or gum Arabic is the dried gummyexudation obtained from the stem and

branches of Acacia Arabica wild, belonging to (Leguminosae). The gum has been recognized as

an acidic polysaccharide containing D-galactose, L-arabinose, L-rhamnose, and D-glucuronic

acid. Acacia is mainly used in oral and topical pharmaceutical formulations as a suspending and

emulsifying agent, often in combination with tragacanth. It is also used in the preparation of

pastilles and lozenges and as a tablet binder.56 Gum Arabic was successfully used as a matrix

microencapsulating agent for the enzyme, endoglucanase, which proofed to give a slow release of

the encapsulated enzyme and in addition increased its stability.57 Gum Arabic was used as an

osmotic suspending and expanding agent to prepare a monolithic osmotic tablet system. The

optimum system delivered the water-insoluble drug, naproxen, at a rate of approximately zero

order for up to 12 hours at a pH of 6.8.58 Sustained release of ferrous sulphate was achieved for 7

h by preparing gum Arabic pellets. The release was further sustained for more than 12 h by coating

the pellets with polyvinyl acetate and ethylene vinyl acetate, respectively. An increase in the

amount of gum Arabic in the pellets decreased the rate of release due to the gelling property of

gum Arabic. The gel layer acts as a barrier and retards the rate of diffusion of FeSO4 through the

pellet. 59

Karaya Gum :Karaya gum is obtained from Sterculia urens (Sterculiaceae) is a partially acetylated

polymer of galactose, rhamnose, and glucuronic acid. Swellable hydrophilic natural gums like

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xanthan gum and karaya gum were used as release-controlling agents in producing directly

compressed matrices. Caffeine and diclofenac sodium, which are having different solubilities in

aqueous medium were selected for gum erosion, hydration and drug release studies using a

dissolution apparatus (basket method) at two agitation speeds. It was concluded that drug release

from xanthan and karaya gum matrices depended on agitation speed, solubility and proportion of

the drug. Both xanthan and karaya gums produced near the zero order drug release with the erosion

mechanism playing a dominant role, especially in karaya gum matrices. 60 It was shown that

mucoadhesive tablets prepared by karaya gum for buccal delivery, had superior adhesive

properties as compared to guar gum and was able to provide zero-order drug release, but

concentrations greater than 50% w/w may be required to provide suitable sustained release. 61

Tragacanth :This gum is obtained from the branches of Astragalus gummifer (Leguminosae). 22

Tragacanth contains from 20% to 30% of a water-soluble fraction called tragacanthin (composed

of tragacanthic acid and arabinogalactan). It also contains from 60% to 70% of a water-insoluble

fraction called bassorin. Tragacanthic acid is composed of D-galacturonic acid, D-xylose, L-

fructose, D-galactose, and other sugars. Tragacanthin is composed of uronic acid and arabinose

and dissolves in water to form a viscous colloidal solution (sol), while bassorin swells to form a

thick gel.62 Tragacanth when used as the carrier in the formulation of 1-and 3-layer matrices

produced satisfactory release prolongation either alone or in combination with other polymers.63

has been used since ancient times as an emulsifier, thickening agent, and suspending agent.67

Aloe Gel: The inner part of the leaves of Aloe Vera (L.) Baum. f. (Aloe barbadensis Miller)

consists of the parenchyma tissue that contains the mucilaginous gel.68 After extraction of the A.

Vera gel from the leaves and a filtration step, the acetone precipitate was directly compressed in

matrix systems with diclofenac sodium as a model drug. The mucilage produced direct

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compressible matrix tablets that showed good swelling and sustained release of the model drug.

69 Many of the health benefits associated with Aloe Vera have been attributed to the

polysaccharides contained in the gel of the leaves. These biological activities include promotion

of wound healing, antifungal activity, hypoglycemic or antidiabetic effects antiinflammatory,

anticancer, immunomodulatory and gastroprotective properties. These effects include the potential

of whole leaf or inner fillet gel liquid preparations of A. Vera to enhance the intestinal absorption

and bioavailability of co-administered compounds as well as enhancement of skin permeation. In

addition, important pharmaceutical applications such as the use of the dried A. Vera gel powder

as an excipient in sustained release pharmaceutical dosage forms.70

Psyllium : Psyllium mucilage is obtained from the seed coat of Plantago ovata by milling the outer

layer of the seeds. It has been evaluated for its tablet binding properties, 79 but also to form

hydrogels through radiation-induced cross-linking for controlled release of 5-fluorouracil as a

model drug.80Psyllium and methacrylamide based hydrogels were prepared by using N,N’-

methylenebisacrylamide as a cross-linker, which were then loaded with insulin. These cross-linked

hydrogels showed controlled release of the active ingredient by means of non- Fickian diffusion

of the drug through polymer chain relaxation during swelling.81 Psyllium husk was used in

combination with other excipients such as hydroxypropyl methylcellulose to prepare a novel

sustained release, swellable and bioadhesive gastroretentive drug delivery systems for

ofloxacin.82

Xanthan Gum: Xanthan gum is a high molecular weight extracellular polysaccharide produced by

the fermentation of the gram-negative bacterium Xanthomonas campestris. The primary structure

of this naturally produced cellulose derivative contains a cellulosic backbone (ß-D-glucose

residues) and a trisaccharide side chain of ß-D-mannose-ß-D-glucuronicacid-a-D-mannose

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attached with alternate glucose residues of the main chain. In one of the trials, xanthan gum showed

a higher ability to retard the drug release than synthetic hydroxypropylmethylcellulose. Xanthan

gum and hydroxypropylmethylcellulose were used as hydrophilic matrixing agents for preparing

modified release tablets of diltiazem HCl

NATURAL POLYMERS FROM ANIMAL ORIGIN

Chitin: Chitin is the polysaccharide derivative containing amino and acetyl groups and are the most

abundant organic constituent in the skeletal material of the invertebrates. It is found in mollusks,

annelids, arthropods and also as a constituent of the mycelia and spores of many fungi. 22 It may

be regarded as a derivative of cellulose, in which the hydroxyl groups of the second carbon of each

glucose unit have been replaced with acetamido (-NH(C=O)CH3) group. The new polyelectrolyte

complex gel beads based on Phosphorylated Chitosan (PCS) were developed for controlled release

of ibuprofen in oral administration. The PCS gel beads were readily prepared from soluble

phosphorylated chitosan by using an ionotropic gelation with counter polyanion, tripolyphosphate

(TPP), at pH 4.0

Gelatin : Gelatin (from Latin: gelatus meaning "stiff", "frozen") is a translucent, colourless, brittle

(when dry), flavourless solid substance, obtained by partial hydrolysis of collagen derived from

skin, white connective tissue and bones of various animals such as domesticated cattle, chicken,

pigs, and fish. Photographic and pharma grades of gelatin are generally made from beef bones

Uses • It is used in preparation of suppositories, pastes, pastilles, coating of tablets and formation

of hard and soft capsule shells. • It is used for microencapsulation of drugs. • Gelatin typically

constitutes the shells of pharmaceutical capsules in order to make them easier to swallow.

Hypromellose is a vegetarian-acceptable alternative to gelatin, but is more expensive to produce.

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Saxena et al (2011) prepared agar-gelatin compositions and tablets made of agar, gelatin A gelatin

B and their blends agar-gelatin A, agar-gelatin B, gelatin A-gelatin B in 1:1 ratio.

Application of Gums and Mucilage

Hydrogel:

Hydrogels, are polymer networks extensively swollen with water. Hydrophilic gels that are usually

referred to as hydrogels are networks of polymer chains that are sometimes found as colloidal gels

in which water is the dispersion medium.

Researchers, over the years, have defined hydrogels in many different ways. The most common of

these is that hydrogel is a water-swollen, and cross-linked polymeric network produced by the

simple reaction of one or more monomers. Another definition is that it is a polymeric material that

exhibits the ability to swell and retain a significant fraction of water within its structure, but will

not dissolve in water. Hydrogels have received considerable attention in the past 50 years, due to

their exceptional promise in wide range of applications. They possess also a degree of flexibility

very similar to natural tissue due to their large water content. The ability of hydrogels to absorb

water arises from hydrophilic functional groups attached to the polymeric backbone, while their

resistance to dissolution arises from cross-links between network chains. Many materials, both

naturally occurring and synthetic, fit the definition of hydrogels. During last two decades, natural

Hydrogels were gradually replaced by synthetic hydrogels which has long service life, high

capacity of water absorption, and high gel strength. Fortunately, synthetic polymers usually have

well-defined structures that can be modified to yield tailor able degradability and functionality.

Hydrogels can be synthesized from purely synthetic components. Also, it is stable in the conditions

of sharp and strong fluctuations of temperatures

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Recently, hydrogels have been defined as two- or multi-component systems consisting of a three-

dimensional network of polymer chains and water that fills the space between macromolecules.

(Ahmed 2015)

Biomaterial Film:

Biomaterial films can be edible or inedible depending on the raw materials, preparation process

and end use. Typical biopolymers used to prepare edible films are cereal proteins and

polysaccharides including starch, milk proteins, root and tuber starches. An advantage of

biopolymer films is that they are generally biodegradable and also renewable, thus they could

reduce environmental load. However, synthetic packaging materials can not be replaced fully by

biomaterials because they the former better mechanical properties.

Film forming materials, such as starches, proteins and polyols, are used for different purposes in a

biomaterial and/or edible film preparation process. Biopolymers like starches and proteins create

the basic network structure of the film. However, films prepared from biopolymers are often too

fragile to stand handling, e.g., bending or stretching. Thus, they have to be plasticized using low

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molecular weight substances, such as polyols, which decrease interactions between the biopolymer

chains. Due to plasticization better handling properties may be obtained whereas other properties,

such as water sorption, gas permeability and mechanical properties, may weaken.

Biopolymers used in film preparation are often carbohydrates or proteins extracted or separated

from plants, animal tissues or animal products. The storage carbohydrate in plants is starch.

Depending on the plant the starch is formed in different parts of the plant, e.g., grain, tuber or root

(Banks and Greenwood, 1975). Other carbohydrates found in the plants e.g. the cell wall include

cellulose and pectin (MacDougall and Ring, 2004). Some carbohydrates, such as alginate and

carrageenan, are found in seaweeds (Ramsden, 2004). Cereal grains contain, in addition to starch,

protein, such as gluten (wheat) and zein (maize) (Bergthaller, 2004). Biopolymers extracted from

animal products or parts are also used in edible film manufacturing. Casein and whey proteins are

separated from milk and they are often used to prepare films (McHugh and Krochta, 1994a).

Gelatin is a derivative of collagen a protein which can be extracted from animal skin or bones

(Arvanitoyannis, 2002). Gelatin may be used to produce edible film, e.g., for food preservation

and pharmaceutical capsules (Arvanitoyannis, 2002).

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MATERIALS AND METHODS:

Materials

All materials and reagents used in the study were of AR grade and were purchased from SD Fine

Chemicals, Mumbai (India) ,Sigma Aldrich, USA.

Authentication of Plant Material

Authentication of plant materials was done by Department of Botany, Bharathi Women’s College,

Chennai 108. Voucher specimens deposited in raw drug collection of the Department.

Collection of Gums and Resins from Plants

Gums were collected from the injured sites of plants across Tamil nadu. Resins were purchased

commercially.

Extraction

Extraction Procedure: Almond (Prunus dulcis) was obtained from various local markets of

Chennai. Extraction of gum was carried out as per the following: Powdered fruit was put in

1000ml beaker containing 500ml of distilled water, then heated and stirred continuously at 60°C

for approximately 4h. Concentrated solution was filtered through muslin cloth and cooled at 4°-

6°C. The extract added with ethyl alcohol, thus precipitation of the gum occurred. The precipitated

solution was filtered using muslin cloth. Gum was immersed in petroleum ether for 5h to remove

oil content. Dried polymer was powdered and stored in a desiccator for further studies.

Physical characterization

The extracted biopolymer was evaluated for physical characteristics like. Appearance, odor,

solubility, percentage yield, swelling ratio, pH.

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Moisture content

Moisture content of samples was determined by drying 5g of the ground gum sample to constant

mass at 800ºC using a hot air oven. Dried samples were cooled in a desiccator before weighing.

Moisture content was expressed as % of mass loss from the original mass.

pH

pH of 25% aqueous gum solution (w/v) was measured using a glass electrode pH meter

Water solubility

Gums are uncrystallizable. The solubility of samples in water was determined at room temperature

(30°C) by adding 10mg of the sample to 10cm3 of distilled water and leaving the mixture

overnight. 15cm3 of the clear supernatant was then taken in a small pre-weighed evaporating dish

and heated to dryness over a water bath. The mass of the dried residue with reference to the volume

of the solution was determined using a digital top loading balance and expressed as the % solubility

of the gum in water (Carter, 2005).

Swelling Index

Swelling index was evaluated using protocols of Bhumkar et al (2006). Briefly, dried samples (10

g, initial weight-Wi) was soaked in 250ml deionized water at 37± 0.2°C for a period of 72 hours.

Samples were withdrawn at 4 hours interval and an increase in weight (Wf) was measured after

gently blotting the excess water. Swelling index (S.I) was calculated using following formula

Wf - Wi

Swelling Index = ---------------- X 100

Wi

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Chemical characterization

The extracted biopolymer was tested for chemical characteristics [5-6] like test for carbohydrates,

test for chlorides, test for proteins and test for sulfate. Using the standard protocols.

Purification of gum:

The gum was collected from trees (Injured site). It was dried, ground and passed through sieve no

80. Dried gum (10g) was stirred in distilled water (250ml) for 6-8 hours at room temperature.

Preparation of Hydrogel from Moringa and Almond Gum

The dried gum of Prunus amygdalus was thoroughly cleaned to remove all foreign materials

adhered to the surface of the gum, the gum was dissolved in warm water, reprecipitated using

ethanol (1:1), dried at 40º C, powdered and stored in airtight container at room temperature.

Identification Tests for Hydrogels

The identification of the isolated polysaccharide hydrogels was carried out by using the procedures

of Shriram et al 2012.

a. The powder was mounted on a slide with ruthenium red solution and covered with a cover slip.

After a few seconds, it was irrigated with lead acetate and the excess stain was sucked off with a

blotting paper. (Lead acetate solution was added to prevent undue swelling of the test solution).

The color of the particles was noted.

b. The powder sample was mounted on a slide with freshly prepared corallin soda solution and

covered with a cover slip. After a few seconds it was irrigated with 25% sodium carbonate solution.

The color of the particles was noted.

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c. Hydrogel was heated with distilled water for some time and then cooled. Formation of gelatinous

mass was noted.

d. To 2 ml of hydrogel solution, 2-3 drops of N/50 iodine solution was added and the color of the

particles was noted.

Determination of Purity of Hydrogels

Purity of the hydrogels was checked by carrying out qualitative tests for alkaloids, carbohydrates,

flavonoids, steroids, amino acids, terpenes, saponins, oils and fats, tannins and phenols

Organoleptic Evaluation of Hydrogels

The isolated hydrogels were characterized for organoleptic properties such as color, odor, taste,

fracture and texture.

Ash Values of Hydrogels

Ash values such as total ash, acid insoluble ash and water-soluble ash were determined by methods

described in Indian Pharmacopoeia.23 For determination of different ash values, the hydrogel was

powdered and the powder was passed through British Standard Sieve (BSS) no. 40. The following

procedures were used for determination of different ash values.

Total Ash

Accurately weighed hydrogel (3 g) was taken in a silica crucible, which was previously ignited

and weighed. The powder was spread as a fine, even layer at the bottom of the crucible. The

crucible was incinerated gradually by increasing temperature to make it red hot until free from

carbon. The crucible was cooled and weighed. The procedure was repeated to get constant weight.

The percentage of total ash was calculated with reference to air-dried drug.

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Acid Insoluble Ash

The ash obtained as described above was boiled with 25 ml of 2 N hydrochloric acid for 5 min.

The insoluble ash was collected on an ashless filter paper and washed with hot water. The insoluble

ash was transferred into a silica crucible, ignited and weighed. The procedure was repeated to get

a constant weight. The percentage of acid insoluble ash was calculated with reference to the air-

dried drug.

Water Soluble Ash

The ash obtained as described in the determination of total ash was boiled for 5 min with 25 ml of

water. The insoluble matter was collected on ash less filter paper and washed with hot water. The

insoluble ash was transferred into silica crucible, ignited for 15 min, and weighed. The procedure

was repeated to get a constant weight. The weight of insoluble matter was subtracted from the

weight of the total ash. The difference of weight was considered as water-soluble ash. The

percentage of water-soluble ash was calculated with reference to the air-dried drug.

Solubility Behavior of Hydrogels

One part of dry hydrogel powder was shaken with different solvents & solubility was found out.

pH of Hydrogels

The hydrogels were weighed and dissolved in water separately to get a 1%w/v solution. The pH

of each solution was determined using digital pH meter.

Swelling Index of Hydrogels

The swelling index is the volume (in milliliters) taken up by the swelling of 1 g of test material

under specified conditions. The swelling indices of the selected hydrogels were determined by the

method described by WHO.24. Accurately weighed quantity of the hydrogel (1 g), previously

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reduced to the required fineness, and was introduced into a 25 ml glass-stoppered measuring

cylinder. Twenty five milliliters of water was added and mixture was shaken thoroughly every 10

min for 1 h. It was then allowed to stand for 3 h at room temperature. Then the volume occupied

by the hydrogel, including any sticky mucilaginous portion was measured. The same procedure

was repeated thrice and the mean value was calculated.

Loss on Drying

Loss on drying is the loss in weight in percentage w/w, resulting from water and volatile matter of

any kind that can be driven off under specified conditions. The test was carried out according to

the procedure described in Indian Pharmacopoeia.23.One gram of hydrogel powder was weighed

accurately in a tarred glass stoppered bottle and was dried in a hot air oven at 105 C and the

weight was checked at intervals of 1 h, until a constant weight was obtained. The weight difference

was noted and the percentage of weight lost by the powder was calculated.

Moisture Absorption

The hydrogel sample (10 g) was placed in an open glass dish of 50 mm diameter and 30 mm height

in a desiccator over sulfuric acid (14%) and it was allowed to remain for 24 h. The increase in

weight was noted and expressed as percentage moisture absorption.26

Incorporation of drug into hydrogel

Encapsulation of drugs was carried out by incubation method as summarized by No et al (2002)

and Adhirajan et al (2007). Briefly, drugs viz Amoxylin, Taxim and Nystatin were encapsulated

in Hydrogels by adding 5 grams of unloaded hydrogel powder to 10ml of solution containing the

said drugs at 2mg/ml concentration, incubated at 37±1°C for 72 hours. Subsequently, loaded

hydrogels were freeze dried and stored at -20°C till use.

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Drug release studies

Invitro drug release study was carried out by dialysis method (Tsipouras et al 1995, Esposito et al

1996). Briefly, drug loaded hydrogels were re-dispersed in 10ml of distilled water in dialysis

membrane bag (10kDa molecular cut-off) and placed in 40 ml of physiological synthetic serum

electrolyte solution (SSES) of pH 7.4 at 37°C, with constant stirring at 75 RPM. Aliquot of 5ml

was withdrawn at 4 hours intervals for a period of 72 hours and drug content was quantified

through optical density measurements.

Preparation of Biopolymer sheets/ Films:

The polymer film was prepared from the polymers extracted from Almond and Morinda gum .

the polymers were allowed to swell for 12 hours after which the pH of the hydrogel was altered

using acetic acid and they were allowed to form films on a thick cellophane sheet and 4/6/12 well

plates. The system was left undisturbed for 24 hours at 30°C. The dried films were washed with

500 mL of deionized water for 30 min three times to remove the residual acetic acid. Then, the

samples were immersed in 200 mL of 10 mM Hepes buffer for 30 min and again in 500 mL of

water for 30 min. afterwards, the films were dried at 37°C for 24 h. The films were cut into

appropriate size samples and sterilized by exposure to UV radiation for 30 Minutes.

Characterization of the Films

The samples were characterized with respect to morphology, thickness, absorption and stability in

aqueous solutions, mechanical properties, volumetric expansion as described below.

Morphology

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The overall aspect was analyzed by inspection with the naked eye and recorded using a digital

camera.

Thickness

The thickness of the films was measured with a micrometer in four equidistant positions near the

edge of each film. The results were expressed as mean values.

Water absorption study

Water absorption studies of the bio-composite sheets was determined by cutting the sheets into

2*2cm2 size and initial weight of sheet was recorded. The sheet was then placed in 5ml water

containing beaker and the amount of water taken up by sheet was found by weighing the weight

of swollen sheets after time intervals of 1hr, 2hrs, 3hrs and 24 hrs. Each time the excess water was

blotted before weight measurements were taken. The Percentage water absorption capacity at a

given time was calculated from the formula:

% Water absorption capacity (W.A.C) = [(final weight – initial weight) / (initial weight)]*100

Incorporation of Drug into the film:

A known q uantity of antibiotic Taxim was incorporated into the film by adding it to the mixture.

The presence of the drug in the film was analyzed using FTIR drug release and antibacterial assay.

FTIR analysis :

Fourier transform infra red (FTIR) spectral studies of the prepared sheet was carried out was done

using ATR method. The spectra was measured at a resolution of 4 cm-1in the frequency range

4000–500 cm-1 using Schimadzu Fourier Transform Infrared (FTIR) Spectroscope.

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RESULTS AND DISCUSSION

Gums /, resins and latexes are employed in a wide range of food and pharmaceutical products and

in several other technical applications. They form an important group of non-wood forest products

which are the basis of a multi-billion dollar industry. Gums in particular have greater significance

in the world trade. These groups of compounds come from a variety of plants and are often very

complex in their composition. The only thing that they have in common is that they are sticky and

they are exuded or extracted from plants. Plants latexes and resins have been replaced by synthetic

petroleum products to a large extent but the use of natural hydrogels has expanded. As a natural

defence mechanism to prevent infection or dehydration many trees and shrubs are known to

produce an aqueous thick exudation when the plants bark is injured. Eventually the solution dries

up in contract with sunlight and air and a hard transparent brown-tint glass mass formed. This solid

mass is known as Natural gum.

Selection of plant:

Vateria indica, Canarum strictum ,Styrax benzoin , Acacia Senegal, Acacia arabica, Moringa

oleifera, Bombax ceiba, Prunus sulcis, Cassia tora, Pistacia lentiscus were selected for the current

study. Of the ten plants six plants yielded gums and four plants yielded resins. Resins were

purchased commercially and used for the study. While the Gums used in the present study was

collected from the plants. ( Table 1)

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Collection and Isolation of Gums:

Gums were collected from the injured site or by creating wound at the site. Resins were purchased

from market. organoleptic properties, solubility, physio-chemical properties of Gums and resins

are enlisted below (Table 1). Based on the results obtained from the basic screening. It was vivid

that Gums were readily soluble or miscible with water. Hence it was decided that the to carry out

further studies with the plant derived Gums. Hence based on swelling ratio further work was

proceeded with Gums of Prunus and Cassia.

Isolation of Hydrogels:

After hot water extraction and acetone treatment, Prunus gum yielded 70% w/w of hydrogel. The

isolated hydrogels were subjected to identification tests using ruthenium red, corallin soda and by

dissolving them in hot distilled water. With ruthenium red and corallin soda, the particles stained

pink and a gelatinous mass was formed when the powder was heated with distilled water. All these

tests indicated that the isolated hydrogels were polysaccharide mucilages. In the iodine test, the

particles did not stain blue, indicating the absence of starch.

The results of purity tests of hydrogels showed the presence of carbohydrates. Other

phytoconstituents were absent in the isolated powder. This can be considered as proof for purity

of the isolated hydrogels (Table 2). Further characterization of hydrogels was done by determining

the organoleptic properties like color, odor, taste, fracture and texture. Prunus gel was white in

color, did not possess any odor and the taste was bland. The fracture was rough and texture was

irregular for both the isolated hydrogels.

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Table 2 showing the chemical characterization of the Hydrogels

Hydrogel from Prunus Hydrogel from Cassia

Carbohydrates + +

Proteins -- --

Fats -- --

Alkaloids -- --

Phenols -- --

Ash values can be used as standards for the quality control of plant based materials. For the isolated

hydrogels, total ash, acid-insoluble, and water-soluble ash values were determined and are shown

in Table 3. All these values were within the limits for natural polysaccharide polymers.23.

Table 3 showing the Ash values

Total ash Acid

soluable

ash

Water

soluble

ash

Prunus

Gel

3.5 1.2 0.80

Cassia

gel

.2 2.2 0.9

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The solubility test for hydrogels showed that both the hydrogels formed viscous colloidal

dispersions with warm water, and were insoluble in organic solvents such as ethanol, benzene,

butanol, chloroform, and ether (Table 4).

Table 4 showing the solubility of Hydrogels in various solvents

Solvent Prunus Gel Cassia Gel

Cold water

Warm water Forms a viscous colloidal

dispersion immediately

Forms a viscous colloidal dispersion

immediately

Benzene Insoluble Insoluble

Ether

Acetic acid Forms a viscous colloidal

dispersion immediately

Forms a viscous colloidal dispersion

immediately

chloroform Insoluble Insoluble

Ethanol

The pH values of 1% solution of the hydrogels were found to be slightly acidic, which indicated

that hydrogels were non-irritating to the mucous membrane of buccal cavity and gastrointestinal

tract, and both could be used for the development of buccal and oral drug delivery systems. Prunus

gel were found to swell 20.81 mL indicating good water absorption, and hence, formation of a

hydrated three-dimensional network from which the drug release might follow diffusion. The

results of test for loss on drying and moisture absorption are shown in Table 5.

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Table 5 showing pH and swelling index

pH of 1% solution Swelling Index (mL)

Prunus Gel 5.2 20.8

Cassia Gel 3.2 18.66

The absorption of moisture by any substance represents hygroscopic nature of the substance. If

excipient is hygroscopic, it can alter many properties of the dosage forms. Hence, it is necessary

to determine the hygroscopic nature of the excipient and the amount of moisture that can be

absorbed by the excipient. The result of the present study indicated that hydrogels were

hygroscopic and need to be stored in air-tight containers.

The total microbial load of the selected polysaccharide hydrogels is given in Table 7. The total

microbial load is an important parameter which decides the suitability of a substance for use as

excipient in pharmaceutical dosage forms. According to many Pharmacopoeias, for synthetic and

semi-synthetic substances, the total aerobic count should not be more than 100 colony forming

units (cfu) per gram, and the total fungal count (including yeasts and molds) should not exceed 50

cfu/g. In case of excipients from natural origin, the total aerobic count should not be more than

1000 cfu/g and total fungal count should not exceed 100 cfu/g. In the present study, both the

hydrogels exhibited bacterial and fungal counts less than the specified limits and the pathogenic

organisms were absent in both the polysaccharides after purification.

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Table 6 Microbial Load in the hydrogel

Total Bacterial Count

cfu/g

Total fungal count

cfu/g

Prunus gel 85 70

Cassia Gel 87 72

Non-haemolytic nature of Prunus and Cassia gel has been recorded in the present study further

confirms hence considered as blood compatible.

Drug Encapsulation:

In the present study, encapsulation efficiencies of Amoxillin, Taxim and Nystatin on Hydrogels of

Prunus ranged from 30-35mg/150mg hydrogel and 28-30 mg/150 mg hydrogel in Cassia . Similar

to swelling studies, active entrapment of drugs was observed during early phase (0-8 hours)

followed by passive phase (till 72 hours). At end of 72 hours, 92% of the drug was entrapped

(Figure 1). Similar results was obtained with Cassia hydrogels however they differed each other

in the drug encapsulation capacity. A representative graphical representation is presented in Figure

1. Encapsulation efficiency of active constituents within nanospheres varied widely with the

nature of the active constituents. From the previous reports, the encapsulation efficiency of

microspheres ranged between 60-80% (Ribeiro et al 1999; Pandey et al 2004). Requena et al

(2008) reported encapsulation of leu-enkephalin in core-shell isobutylcyanoacrylate-thiolated

chitosan nanoparticles with encapsulation efficiency of 25-46%. Gazori et al (2009) reported

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encapsulation of antisense oligonucleotides in chitosan nanospheres with loading efficacy of

95.6%. Das et al (2010) encapsulated curcumin in alginate-chitosan-pluronic composite

nanoparticles with encapsulation efficiency of 12-15%. Zhang et al (2010) reported BSA

encapsulation efficiency in range of 40- 95% within chitosan nanospheres.

Drug release

With regard to release profile of Amoxillin, Taxim and Nystatin from Hydrogels ( Prunus and

Cassia) with respect to time (Figure 2), we observed an initial rapid release during 0-8 hours,

followed by gradual decrease in release pattern (9-48 hours) and during third phase (48 to 72

hours), there was a decline in the release of drugs. During initial phase, 50% of the drugs were

released and 78% release was observed during second phase and more than 95% drug release was

noticed at the end of 72 hours. Zhang et al (2010) and Das et al (2010) reported the similar drug

release pattern of drug encapsulated in chitosan nanospheres. In the preliminary antimicrobial

study it was found that the drugs which leached out of the hydrogels were able to inhibit the growth

of bacteria and fungi

Figure 1 Drug encapsulation in Hydrogels

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Figure 2 Drug release in Hydrogels

Sheets /Films

Most biopolymers are hydrophilic and, thus, water is the solvent used most often to dissolve

biopolymers to obtain film forming solutions. Instead of water some other solvents with or without

water can be used to dissolve biopolymers. Usually, heating with solvent is needed to disrupt the

native structure of the biopolymer to obtain a film forming solution. Plasticizer is added to the film

forming solution at a convenient stage of the process to obtain flexible and elastic films which are

often desired. There are various biomaterial film forming processes such as casting, spraying,

extrusion and thermo-molding. The most common process to produce films on a laboratory scale

is casting, which is used to produce free films for testing. In this process, a film forming solution

is cast on a non-adhesive surface. Water or solvent is evaporated from the solution in order to form

the film (e.g., Anker et al., 2001; Lazaridou and Biliaderis, 2002; Rindlav-Westling et al., 2002).

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As a result of solvent evaporation, biopolymer increases with the result that hydrogen bonds are

formed and basic film structure is created. Environmental properties, such as temperature and air

relative humidity, during the evaporation stage could be used to control some of the film properties

(Rindlav et al., 1997; Rindlav-Westling et al., 1998; Kawahara et al., 2003).

Morphology:

In the present case the film formation initiated around 8 hours of drying and completed after 24

hours. The film was not brittle and was of uniform thickness. Mathew and Dufresne, 2002

reported film formation using starch prepared by heating to gelatinize starch in excess water in

which plasticizer is added before gelatinization (Mathew and Dufresne, 2002; Mehyar and Han,

2004) or after gelatinization into the hot solution (95°C) (Krogars et al., 2002). In the present case

no external plasticizer was added the polymers when mixed in the ratio of 60:40. Upon addition

of the moringa polymer the initiation towards formation of the film started. Given the same

condition the polymers of almond were not able to form the film same was the case with the

moringa polymer where the film formation was not initiated however the hydrogel formation was

achieved. On addition of both the polymers the film formation was initiated. Unlike the present

study Rindlav-Westling et al., 2002 reported that s film forming suspension containing native

starch, amylose, amylopectin or mixture of amylose and amylopectin is heated in a pressurized

vessel to complete amylose and amylopectin leaching into the solution (Mathew and Dufresne,

2002; Myllärinen et al., 2002a). After gelatinization, the film forming solution is poured onto a

non-adhesive plate, such as polytetrafluoroethylene (teflon ). In the present study there was

absolutely no need for the non-adhesive plate. It was enough for a normal cellophane paper to

substitute the Teflon material. Hence this method is more economical when compare to the above

said study.

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Water is evaporated from the film forming solution to obtain films at various conditions, e.g., at

the room temperature at the controlled RVP conditions (Rindlav-Westling et al., 2003; Mehyar

and Han, 2004) or in an oven at elevated temperatures (Mathew and Dufresne, 2002; Myllärinen

et al., 2002a; Mali et al., 2006). These different drying conditions affect film properties because of

different settling times of biopolymers. The longer the film formation takes the longer time there

is for a film component to phase separate and crystallize. Rindlav-Westling et al. (2003) have

reported small and less aggregated amylose phases in the starch film for shorter drying times. Films

prepared from starch or starch with added amylopectin resulted in a phase separated structure in

the film (Rindlav-Westling et al., 2002). Moreover, structure of film prepared using starch with

added amylose was more homogeneous, but crystallinity of films was higher than that of film

produced from starch only (RindlavWestling et al., 2002). In the present case drying was possible

even in room temperature. When dried in the oven at 37C the film was prepared within 20 hours.

While the time taken for air drying at room temperature was little longer (24-36 hours). However

the flexibility of the film is better when it is air dried than that of the oven dried film. (Figure 3)

Figure 3 Film formed from Polymers of Prunus and Morinda

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Thickness: the average thickness of the film was 57±2µm.

Water absorption capacity:

The water absorption capacity and tensile strength of the sheets were evaluated. Water absorption

capacity of a biomaterial plays a major role in absorption of wound exudates, which helps to keep

the wound surface dry preventing bacterial infection and also provide moist environment16. It also

depends on the microstructure and hydrophilic property of the material. .It was observed that water

absorption capacity Water absorption capacity of the sheets increased with increase in time. Upon

incorporation of the drug it is found to have an effect on the increased hydrophilicity. If the drug

is hydrophilic then the tendency of water absorption capacity is more.

FTIR studies:

The distinct peaks of pure Taxim was found at 1262,1370,1532,1651,1754,cm1, while the polymer

of Prunus- Morinda film showed peaks at 2128,16701447, The film incorporated with the drug

showed the presentce of characteristic peaks of the drugs at 1256, 3443confirming the presence of

the drug taxim in the film. In a similar experiment by Rahim et al 2014 showed the presence of

diclonofac sodium in prunus gum. (Table 7; Figure 4)

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Figure 4 showing the FTIR spectra

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Polymer

Polymer

with

Drug Drug

470 629 526

556 982 553

563 1030 624

761 1134 77

970 1256 975

1077 1423 1044

1447 1434 1179

1670 1596 1262

1733 1634 1370

2128 1709 1532

2355 1875 1651

2956 2130 1754

3388 2349 2348

3561 2922 2584

3570 3101 2932

3610 3443 2949

3518 3038

3590 3255

3623 3342

3443

3576

Table 7 showing characteristic peaks

Carbonyl compounds are those that contain the C=O functional group. In aldehydes, this group

is at the end of a carbon chain, whereas in ketones it’s in the middle of the chain. As a result, the

carbon in the C=O bond of aldehydes is also bonded to another carbon and a hydrogen, whereas

the same carbon in a ketone is bonded to two other carbons. Aldehydes and ketones show a strong,

prominent, stake-shaped band around1710 - 1720 cm-1 (right in the middle of the spectrum). This

band is due to the highly polar C=O bond. Because of its position, shape, and size, it is hard to

miss. Because aldehydes also contain a C-H bond to the sp2 carbon of the C=O bond, they also

show a pair of medium strength bands positioned about 2700 and 2800cm-1. These bands are

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missing in the spectrum of a ketone because the sp2 carbon of the ketone lacks the C-H bond.

These indicate that the given polymer is a carbohydrate in nature.

Antibiotic assay:

In the antibiotic assay carried out using disc diffusion method it showed appreciable antibacterial activity

indicating the presence of drug in the polymer.

CONCLUSION

In the present study gums, Mucilage and resins from ten different plant sources were taken and

analyzed physically, and chemically. Hydrogels were prepared from Prunus and Cassia sp. with

the partially purified polymers. The hydrogels were tested for this physical and chemical nature.

Drug loading capacity and drug release capacity of the polymers were found. A thin

film/Membrane was made using polymers of Prunus and Morinda. The Film was characterized

by Physical and Chemical methods. Drug holding capacity of the film was tested using FTIR and

Antibiotic assay. This study suggest that the polymers of Prunus and Morinda in combination

produces a film which is flexible, has higher water holding capacity and the membrane can also

be loaded with antibiotic. The incorporated drug is also able to leach out under given conditions.

These results suggest that these polymers can be used as potential candidate in the drug delivery

system.

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Table 1 showing organoleptic, Physio-chemical characterization of Gums/ Resins

Vat

eria

indi

ca L

.

Can

ariu

m s

tric

tum

Rox

b

Styr

ax b

enzo

in

Aca

cia

Sene

gal w

ild

Aca

cia

arab

ica

Wil

d

Mor

inga

ole

ifer

a La

m

Bom

bax

ceib

a

Pru

nus

sulc

is

Cas

sia

tora

L

Pis

taci

a le

ntis

cus

1. Type Resin Resin Resin Gum Gum Gum Gum Gumi Gum Resin 2. Appearance crystal Amorphous Crystal Crystal Crystal crystal powder crystal powder crystal 3. Odor Characteristic Strong NO characteristic odor Characteri

stic 4. Colour White Brown Black Yellow Brown Dark

Brown Brown Half

white Black Yellow

5. Solubility in water

Insoluble Soluble/Miscible Insoluble

6. Swelling -- -- -- 17.8 17.69 20.07 17.69 20,81 20.66 -- 7. pH -- -- -- 5 5 7 5 5 3 -

8. Carbohydrates Negative

Positive Negative 9. Proteins Mild presence 10. Lipid Negative Positive 11. Alkaloid No characteristic response 12. flavonoid

13. Terpenes