1. INTRODUCTION:

Natural gums and mucilage are carbohydrate polymers of high molecular weight obtained from plant source. They can be dispersed in cold water to give viscous and mucilaginous solution that normally does not gel. They are composed of acidic/neutral monosaccharide building units joined by glyosidic bonds. Gums are particularly important in food processing where they are used as emulsifying, stabilizing and thickening agents. They also function as gelling, bodying agents, foam enhancers and suspending agents, seal wound, dental formulations, adhesives and bulk laxatives [1,2]. Gums and mucilage may be found either in the intracellular part of plants or extracellular exudates.

Those found within plant cells represent storage material in seeds and roots. Gum and mucilage present in roots, tubers and seaweeds are extracted with hot water, dried and marketed as powder. Those present in inner part in inner part of seed coat such as locust gum, guar gum are isolated by milling method. Sustained drug delivery dosage forms improve therapeutic effectiveness of drugs by retarding their release in which polymers used in the formulation are the key performers. Various natural, semi synthetic, synthetic polymers have been investigated for their potential of retarding the drug release in the formation sustained release systems. Synthetic polymers such as ethyl cellulose, hydroxyl propyl methylcellulose when used alone have some specific limitations, combination of polymers used to overcome the limitations make the process complicated and increase the overall cost of formulation, so the recent trend toward the use of plant based polymers demands the replacement of synthetic materials with natural one. Many natural polymers have been successfully explored for their release retarding property in the formulation of sustained released dosage forms. These include guar gum, locust bean gum, tamarind seed gum, agar, gum copal etc [3]. This review gives an insight of certain recently investigated gums and mucilage as matrix forming agent in the formulation of sustained released dosage forms, along with method of extraction of gums and mucilage, their classification, characterization and pharmaceutical applications of gum and mucilage [4 ].

Difference between gums and mucilage [5]:

Difference between gums and mucilage is summarized in Table no 1.

Table 1: Difference between Gums and Mucilage

Gums	Mucilage
Gum get dissolves in water to form gummy mass	Mucilage give slippery mass when dispersed in water
Gums are pathological products of plant	Mucilage are physiological product
Gums are extracellular formations	Mucilage are intracellular and normal metabolic products

1.1 Classification of natural gums and mucilage’s:

Gums and mucilage can be obtained from various natural sources such as plants, animals and microbial where they are known to perform various structural and metabolic functions. As per the different systems of classifications they can be classified depending upon the source from which they are isolated and depending upon the charge carried by the polymer [6].

Depending upon the charge they may ionic and nonionic:

· Ionic: Karaya gum, gum Arabic and Tragacanth

· Nonionic: Locust bean gum, Tamarind and Guar gum.

Depending upon their source they can also be classified as:

· Plant: Gum Arabic, Guar gum, Locust bean gum, Araucaria gum, Albizia gum

· Animal: Chitin, Chitosan, Condrotoin sulfate, Hyaluronic acid

· Microbial: Xanthun gum, Dextran, Curdian, Pullulan gum

1.2 Advantage of natural gums and mucilage:

· They are biodegradable, so mostly used in pharmaceutical and food industry.

· They are Biocompatible and nontoxic in nature because chemically most of these plants materials are carbohydrates and composed of repeating sugar units.

· Economical, it is always cheaper to use natural polymers because production cost is much lower as compared to synthetic polymers.

· India and many developing countries are depending on agriculture and are rich source of natural polymers.

· Local availability, in developing countries government promotes the production of plant like guar gum and tragacanth because of the wide applications in a variety of industries, therefore readily available in the local market.

· Better patience tolerance as there is less chance of side and adverse effects with natural materials compared with synthetic one [7,8].

1. 3 Disadvantages of natural gums and mucilage:

· Microbial contamination, gum and mucilage being isolated from natural sources are highly contaminated with microbial substances.

· Due to differences in the collection of natural materials at different times, as well as differences in region, species, and climate condition the % of chemical constituents present in a given material may vary.

· Reduced viscosity on storage – Due to the complex structure of gums and mucilage it has been found that there is decrease in viscosity on storage, also when gums come into contact with water there is an increase in the viscosity of the formulations [9,10].

1.4 General method used for the Isolation of Gums and Mucilage from natural sources:

General method used for the isolation of gums and mucilages from various plant parts involves the collection fresh plant part material which is washed several times with fresh water for the removal of dust and debris and dried. The finely divided material is then soaked in water for the period of 5-6 hours and boiled for 1 hour and allowed to stand for 24 hours for the complete release of mucilage. The material is then squeezed through the eight fold muslin cloth this is followed by the addition of three volumes of acetone/alcohol to filtrate for complete precipitation of mucilage. The precipitated mucilage is then removed and dried in oven at temperature not exceeding 50 ºC, suitably stored for further characterization [11].

1.5 Characterization of Natural gums and mucilage:

Preliminary confirmatory test for dried gums and mucilage powders are summarized. For characterization, various analytical techniques can be used according to the type of information required.

Structural:

The structure elucidation of gums and mucilages can be carried out by FTIR, Mass, and NMR spectroscopy.

Purity:

To determine the purity of selected gums and mucilage, test for alkaloids, glycosides, steroids, carbohydrates, flavonoids, terpenes, amino acids, saponins, oils fats, tannins and phenols are carried out.

Impurity profile:

Suitable analytical techniques can be used to check the presence of impurities.

Physiochemical properties:

Color, odor, taste, shape, texture, solubility, pH, swelling index, loss on drying, hygroscopic nature, micrometric properties and surface tension can be estimated [12].

Toxicity:

The acute toxicity of gums and mucilage can be determined by fixed dose method as per organization for economic co-operation and development (OCED) guideline no. 425.

Detailed method for the Preliminary confirmatory tests used for the characterization of natural gums and mucilage are discussed in the Table no. 2

Table 2: Preliminary confirmatory tests for the characterization of natural polymers [13]

Test/ method	Observation	Inferences
Molisch’s test: 100 mg of dried mucilage powder and molisch’s reagent and concentration sulphuric acid on the side of test tube	Violet green colour observed at the junction of two layers	Carbohydrate present
Ruthenium test: Take a small quantity of dried mucilage powder mount it on slide with ruthenium red solution and observe under microscope	Pink colour develops	Mucilage present
Iodine test: 100 mg dried mucilage powder and 1ml 0.2 N iodine solution.	No colour observed in solution	Polysaccharides present (starch is absent)

2. Pharmaceutical Application of Natural Polymers:

Natural polymers such gums and mucilage possess a complex branched polymeric structure because of which they exhibit high cohesive and adhesive properties that can be used for pharmaceutical preparations and hence gums have diverse applications in dosage form development. These are useful as tablet binder, disintegrating agent, emulsifier, suspending agent, thickners, gelling agent, stabilizing agent in suspension and drug release sustaining agent in tablets formulation [14].

2.1 Gums as a tablet binder:

Gums find its application in tablets formulation as binder because of their adhesive nature. They impart cohesiveness to the powder mass and convert into granules. Cassia roxbughii seed gum was evaluated as a binder in the formulation of paracetamol and diclofenac sodium granules. It has been found that Cassia roxburghii gum has excellent mechanical, binding and release properties [15]. The binding property magnifier indica gums as tablet binder was evaluated using paracetamol as a model drug. The tablets hardness prepared from magnifera indica varies from 6.3 to 6.8 kg/cm²[16].Khaya gum obtained from incised trunk of khaya grandifolia. Has been shown to possess excellent binding properties and to evaluate its suitability as binding agent paracetamol tablets were formulated. Cashew tree gums was evaluated as binder in metronidazole tablets. Cashew gum is the exudate from the stem bark from of Anacardium accidentale Linn family Anacardiaceae [17].

2.2 Gums as emulsifying and suspending agent:

Gums act as emulsifying and suspending agent. They effectively stabilize the suspension by adsorption at interface and subsequently forming a condensed film of high tensile strength that resist coalescence of droplets. They stabilize oil/water emulsion by forming strong multi molecular film round each oil globule thus retards the coalescence by hydrophilic barrier between oil and water phase. Natural gums increase the hydration of the hydration layer around the suspended particle through hydrogen bonding and molecular interaction [18]. Since these agents do not reduce the surface and interfacial tension, they function best in presence of the wetting agent. They also act as thickener and protective for solid particle to make them suspended for sufficiently long time to maintain the dose uniformity. e.g Cordia gharaf gum colloids. The suspending properties of Cordia gharaf gum were evaluated comparatively with those of compound tragacanth, Acacia and gelatin at concentration range of 0.5%-4.0% w/v in paracetamol suspension [19]. Ablizia zygia gum belonging to family Mimocedeacea was evaluated comparatively with the compound tragacanth, acacia, and gelatin at concentration range 0.5-4.0% w/v in sulphadimine suspension as a suspending agent. Results indicated that due to high viscosity of albizia gum its mucilage can be a stabilizer of choice when high viscosity is required. Natural gums are hydrophilic colloids which form dispersion in water and increase the viscosity of continuous phase so that dispersed particle remain suspended for long period of time without forming aggregates [20].

2.3 Gums as coating agent:

Natural gums also act as tablet coating agent, which can sustain the drug release from the dosage form, or can also prevent the drug from degradation at acidic pH of the stomach, as the number of coating increase the drug release is retarded. Grewia gum was evaluated as a film coating agent in formulation of theophylline tablets [21].

2.4 Gums as microencapsulating agents:

The gums because of their coating ability find application in microencapsulation of drug particles for sustaining the drug release. Gums from acacia nilotica delile, Acaica Senegal wild and amizo gum has been studied for their micrpencapsulating properties using spray drying technique. Among these three Acacia nilotica is reported to be better microencapsulating agent. Other gums used in microencapsulation are gum kondagogu, xanthan, guar gum and mastic gum [22].

2.5 Gums as gelling agent:

Gum can form a gel either alone or in combination with other gelling agents. Gelling is a result of numerous inter and intra molecular association to produce three dimensional network within which water molecule are entrapped such association are brought about by physically such as altering temperature or pH or chemically by the addition of suitable agent. Some of the examples of natural gelling agents used in gel formation are gelatin, alginic acid, xanthan gum and locust bean gum [23].

2.6. Gums as matrix forming materials for sustained release in dosage form:

Gums can be used for sustaining the drug release. Various gums due to their viscous nature from strong matrix in to which drug particles get entrapped or embedded that reduces particle mobility for controlled release. They have been used in tablets dosage forms as matrix systems for sustaining the drug release. These polymers when come in contact with water get hydrated to form gel network and the drug release from this gel is controlled by diffusion of particles and hence release will be sustained over a long period. eg. Guar gum, xanthan gums, karaya gums were studied as release rate barrier in the formulation of oral matrices tablets of propanolol-Hcl as water soluble propanolol Hcl and water in soluble in diclofenac sodium [24].

3. Some Recently Investigated Natural Gums and Mucilage Used in Sustained Released Dosage Forms

Natural gums are polysaccharides which are polymeric in nature obtained from woody and non woody plant parts such as bark, seeds, sap, roots, rhizomes, fruits and leaves. Various plant gums used as matrix forming agents for controlled drug release in tablet formulation are:

3.1. Citrus gum:

Citrus gum is obtained from incised trunk of the tree belonging to family Rutaceae. The gum s polysaccharide consisting of galactose, arabinose, glucose and other sugar residue. Vijaya sri et al carried out studies to establish the potential of citrus gum as a matrix forming agent in the formulation of aceclofenac sustained released tablets. The results obtained indicated that formulation containing citrus gum 20% retard the drug release in a controlled manner and could be used in the sustained release formulations [25].

3.2. Gum Olibanum:

Gum olibanum is a dried, gummy exudation obtained from tress of the genus Boswellia serrata family: Burseraceaae that produce true-frankincense. olibanum consist of acid resin, gum and volatile oil. Ether soluble resin extracted from olibanum exhibit excellent release retarding properties in matrix tablets for controlled release due to its hydrohobic water repellant properties. Gum olibanum is used as anti-inflammatory and as per the recent investigations was found to have positive influence on rheumatism. Kebebe et al reported matrix forming ability of resins of gum olibanum using diclofenac sodium as a model drug [26]. In another study Chowdary et al evaluated the use of gum olibanum in microencapsulation of nifedipine. Resin coated microcapsules exhibited a high encapsulation efficiency and drug release was shown to follow non-Fickian mechanism. Silver nanoparticles synthesized with aqueous extract of gum olibanum was reported to be stable as water soluble component of olibanum serves as both reducing and stabilizing agent [27]. Manujula et al investigated matrix forming property of sustained release tablets of tramadol, a freely water soluble drug. Results of investigations indicated that drug release from matrix tablets was dependent on the concentration of gum olibanum, and largely followed first order kinetics and non fickian type of diffusion [28]. Chowdary et al studied gum olibanum and hydroxy propyl methyl celluose as matrix former for floating tablets on gas generating principle and to design floating tablets of Glipizide. Formulation containing 50% of olibanum gum and 20% of sodium bicarbonate is considered best floating tablets and was found suitable for 24 hours once a day administration [29].

3.3. Okra gum:

Okra gum obtained from the pods of Hibiscus esculents is one of the recently explored polysaccharides that is currently being studied in the pharmaceutical industry as hydrophillic polymer in pharmaceutical dosage forms [30]. An okra plant grows very fast in all soil types, and is among the most heat and drought-tolerant vegetables. It has been investigated as a binding agent for tablets and has also been shown to produce tablets with good hardness, friability, and drug release profiles. It has advantage over most commercial synthetic polymer as it is safe, chemically inert, nonirritant, biodegradable, biocompatible, and ecofriendly, since it is widely harvested and does not require toxicology studies, it is therefore considered to be economical [31]. Nurul Dhania Zaharuddin et al studies the use of okra gum in sustaining the releasing of propranolol hydrochloride in solid oral dosage form. Evaluation of drug release from dissolution studies showed that okra gmm retard the release up to 24 hour and exhibited the longest release as compared to HPMC and sodium alginate [32]. Bakre lateef Gbenga investigated the effect of methods of preparation and concentration of gum on the compression and mechanical properties of okra gum matrix. The results suggested that the concentration of gum and the method of preparation of tablet for compression are critical factors in the formulation of okra gum matrices. Ashwini Rajendera et al developed matrix tablets using poly electrolyte complex formed between Okra gum and chitosan, diclofenac sodium was used as model drug [33]. Shina P et al prepared mucoadhesive beads using okra gum- sodium alginate blend for the controlled release of glibenclamide [34].

3.4. Aegle marmelos gum:

Aegle marmelos gum is obtained from fruits of Aegle marmelos belonging to family Rutaceae is indigenous to india. The ripen fruit pulp is red in colur with mucilagenous and astringent taste. Yogesh joshi et al had undertaken the study to find out the potential of gum from the fruit of Aegle marmelos to act as release modifier in the formulation of diclofenac sodium sustained release matrix tablets [35]. Patil et al formulated the oral tablet of paracetamol by using aegle marmelos fruit gum as a binder in concentration range 2, 4, 6, 8%.Tablets having 6% binder concentration showed optium result as tablet binder [36]. Rohini et al formulated of mucoadhesive tablet by using Aegle marmelos fruit as binder. The formulated tablet showed good tensile strength and mucoadhesion of 10 hrs. From the study it was concluded that the Aegle marmelos gum can be used as excipient for the formulation of mucoadhesive sustained release matrix tablet [37].

3.5. Cissus gum:

Cissus gum is obtained from the stem of Cissus pop-ulnea Guill. And Perr. The plant is a tropical plant belonging to the family Vitaceae. It is gel forming plant. The stems of Cissus populnea are the rich source of gum which can be isolated by incision method [38]. O Adeleye et al studied cissus gum as a controlled release polymer in the formulation of tramadol matrix tablets. Results of the finding indicated that cissus gum showed controlled drug release comparable to xanthan gum and could be used as cheaper alternate to synthetic polymers in the formulation of Sustained released tablets [39].

3.6. Araucaria gum:

Araucaria gum is obtained from bark exduates of the Aaucaria heterophylla family Araucariaceae. The gum obtained from Aaucaria heterophylla as amorphous free flowing powder and possesses the characteristics of carbohydrate and reducing sugars. The gum exhibit dispersibility in water and insoluble in oragnic solvents. In vitro cytotoxicity proved that Araucaria heterophylaa gum can be used as good pharmaceutical excipient for various dosage form. Durga et al carried out investigtion to assess of araucaria gum as a matrix forming agent for the design of oral controlled release tablet dosage forms of diclofenac sodium and compared with the marketed formulation. Matrix tablets were prepared by wet granulation technique and 5%w/v of AHG dispersion water was used as granulating agent for prepartion of AHG matrix tablets. The results indicated that AHG can be used for the development of oral controlled release dosage forms by using matrix systems. [40]

3.7. Ficus carica:

Ficus carica belonging to family moraceae. Ficus carica revealed the presence of bioactive compounds such as phenolic compounds, phystostreols, organic acids, triterpenoids, coumarins and volatile compounds. Ficus carica fruits mucilage was used for the formulation of matrix type transdermal system for controlling release of diclofenac sodium [41]. Mucilage of ficus carica in combination of synthetic polymer polyvinylpyrolidone was used in the formulation of transdermal patches of tramadol hydrochloride to act as matrix forming agent for controlled release of tramadol. Ficus carica mucilage-based patch had a porous surface, and the in vitro drug permeation study revealed that tramadol hydrochloride permeation could be sustained within the therapeutic range [42].

3.8. Artocarpus heterophyllus:

Art carpus heterophyllus Lam. belongs to the family Moraceae and is known by various names in different countries, but is popularly known as jackfruit. Pulp of artocarpus heterophyllus reported to contain plenty of mucilage. M. A. Shende et al carried out studies on the development of sustained release matrix tablets of diltiazem hydrochloride through jackfruit mucilage by direct compression method. Results of the studies carried out indicated that diltiazem matrix tablets using jackfruit mucilage could be prepared with required release control for once daily administration [43]. Vidya Sabale et al carried out isolation and characterization of jackfruit mucilage for the formulation mucoadhesive tablets of chlorphenramine meleate tablets for extended release. Results of in vitro release study indicated sustained drug release with increasing concentration of mucilage [44].

3.9. Mastic gum:

Mastic gum is a resin obtained fom the plant Pistacia lentiscus belonging to family Anacardiaceae. Dinesh M.Morkhade evaluated gum mastic as microcapsulating and matrix forming material for sustained drug release. Mastic gum was characterized for its physiochemical properties. Micro particles were prepared by oil in oil solvent evaporation method. Matrix tablets were prepared by wet and melts granulation techniques using diclofenac sodium and diltiazem hydrochloride as model drugs. Increase mastic drug ratio increased micro particle size, improved drug loading and decreased the drug release. Mastic matrix tablets showed acceptable pharmacy technical properties and sustained drug release. Melt granulation improved efficacy of gum mastic as a matrix forming agent. In vitro drug release followed different mechanism of release kinetics depending upon variable studied. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and micro particles for sustained drug release [45]. Rohan Deshpande et al carried out design of controlled released spheroids of diclofenac sodium using mastic gum by adopting extrusion spheronization technique and evaluated the influence of roll compaction and tableting on the release of diclofenac sodium [46].

4. CONCLUSION:

Natural polymers obtained from various plant parts have been shown to possess wide application as release modifiers, tablet binders, film formers. Thickening agent and disintegrating agent therefore used in pharmaceutical formulation to influence the drug absorption and bioavailability of incorporated drug. However there is continuous need of their modification for their better applicability for the formulation of novel drug delivery systems and biotechnological products. Therefore in the years to come natural gums and mucilage’s find more application in the development of modern pharmaceutical products.

5. CONFLICT OF INTEREST:

Author has no conflict of interest

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Received on 15.03.2019 Modified on 12.04.2019

Research J. Pharm. and Tech. 2019; 12(10): 5119-5125.

DOI: 10.5958/0974-360X.2019.00887.4