Indian Journal of Pharmaceutical Education and Research

Association of Pharmaceutical Teachers of India

Recent Investigations of Plant Based Natural Gums, Mucilages and Resins in Novel Drug Delivery Systems
Amelia M. Avachat*, Rakesh R. Dash and Shilpa N. Shrotriya
Sinhgad College of Pharmacy, 44/1, Vadgaon(Bk.), Pune-411041, Maharashtra, India ABSTRACT
Submitted: 21/4/2010 Revised: 1/7/2010 Accepted: 19/9/2010

All pharmaceutical dosage forms contain many additives besides the active ingredients to assist manufacturing and to obtain the desired effect of the pharmaceutical active ingredients. The advances in drug delivery have simultaneously urged the discovery of novel excipients which are safe and fulfill specific functions and directly or indirectly influence the rate and extent of release and /or absorption. The plant derived gums and mucilages comply with many requirements of pharmaceutical excipients as they are non-toxic, stable, easily available, associated with less regulatory issues as compared to their synthetic counterpart and inexpensive; also these can be easily modified to meet the specific need. Most of these plant derived gums and mucilages are hydrophilic and gel- forming in nature. Recent trend towards the use of plant based and natural products demands the replacement of synthetic additives with natural ones. Many plant derived natural materials are studied for use in novel drug delivery systems, out of which polysaccharides, resins and tannins are most extensively studied and used. This review discusses about the majority of these plant-derived polymeric compounds, their sources, extraction procedure, chemical constituents, uses and some recent investigations as excipients in novel drug delivery systems. KEYWORDS: Plants, gums, mucilage, sustained release, novel drug delivery systems. INTRODUCTION The traditional use of excipients in drug formulations was to act as inert vehicles to provided necessary weight, consistency and volume for the correct administration of the active ingredient, but in modern pharmaceutical dosage forms they often fulfill multi-functional roles such as modifying release, improvement of the stability and bioavailability of the active ingredient, enhancement of patient acceptability and ensure ease of manufacture. New and improved excipients continue to be developed to meet the needs of 1,2 advanced drug delivery systems . Polymers have been successfully investigated and employed in the formulation of solid, liquid and semi-solid dosage forms and are specifically useful in the design of novel drug delivery systems. Both synthetic and natural polymers have 3 been investigated extensively for this purpose . Synthetic polymers are toxic, expensive, have environment related issues, need long development time for synthesis and are freely available in comparison to naturally available polymers. However the use of natural polymers for
Address for Correspondence: Dr. (Mrs.)Amelia M. Avachat, Sinhgad College of Pharmacy, 44/1, Vadgaon(Bk.), Pune411041, Maharashtra, India E- mail:prof _avachat@yahoo.com

pharmaceutical applications is attractive because they are economical, readily available, non-toxic and capable of chemical modifications, potentially biodegradable and with few exceptions and also biocompatible. A large number of plant-based pharmaceutical excipients are available today. Many researchers have explored the usefulness of plant-based materials as pharmaceutical excipients. Ability to produce a wide range of material based on their properties and molecular weight, natural polymers became a thrust area in majority of investigations in drug 4 delivery systems . Natural gums can also be modified to meet the requirements of drug delivery systems and thus can compete with the synthetic excipients available in the market 5 . The fact for increase in importance of natural plant based material is that plant resources are renewable and if cultivated or harvested in a sustainable manner, they can provide a 6 constant supply of raw materials . However, substances from plant origin also pose several potential challenges such as being synthesized in small quantities and in mixtures that are structurally complex, which may differ according to the location of the plants as well as other variables such as the season. This may result in a slow and expensive isolation and purification process. Another issue that has become

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increasingly important is that of intellectual property rights . The plant based polymers have been studied for their application in different pharmaceutical dosage forms like matrix controlled system, film coating agents, buccal films, microspheres, nanoparticles, viscous liquid formulations like ophthalmic solutions, suspensions, implants and their applicability and efficacy has been proven 9-11. These have also been utilized as viscosity enhancers, stabilisers, disintegrants, solubilisers, emulsifiers, suspending agents, gelling agents and bioadhesives, binders in the above mentioned dosage 12 forms . Sustained drug delivery systems significantly improve therapeutic efficacy of drugs. Drug-release-retarding polymers are the key performers in sustained release drug delivery system for which various natural, semi-synthetic and 13 synthetic polymeric materials have been investigated . Besides this several polymers are often utilized in the design of novel drug delivery systems such as those that target delivery of the drug to a specific region in the gastrointestinal tract or in response to external stimuli to release the drug. Most of the investigations of polymers in novel drug delivery are centered on synthetic polymers such as ethyl cellulose 14, 15 16 hydroxypropylmethylcellulose and eudragit . But individually when they have shown specific limitations, different combinations like ethyl cellulose and hydrogenated castor oil 1 7 , eudragit and ethyl cellulose 1 8 , 19 hydroxypropylmethylcellulose and polyamide have been tried to obtain desired drug release profiles. These combinations have ultimately found to make the process complicated and increase the cost of formulation. Recent trend towards the use of vegetable and nontoxic products demands the replacement of synthetic additives with natural one. Many natural polymeric materials have been successfully used in sustained-release tablets. These materials include: guar gum, isapghula husk, pectin, galactomannon from Mimosa scabrella , Gleditsia triacanthos Linn (honey locust gum) , Sesbania gum , mucilage from the pods of Hibiscus esculenta , tamarind seed gum , gum copal and gum dammar, agar, konjac, chitosan etc. 20 . Natural gums and mucilage are composed of many constituents. In several cases, the polysaccharides, resins or the tannins present in the gum are responsible for imparting release retardant properties to the dosage form. Gums are obtained from various parts of the plants. In some of the gums the source may be the epidermis of the seed while on the other hand it may be extracted from the leaf or bark.
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This review gives an insight of plant based novel drugrelease-retarding materials which have been recently studied as carriers not only in the conventional sustained release dosage forms but also in buccal drug delivery systems, gastroretentive systems and microcapsules. Specific reference thus is made to the use of natural polymers in the design of novel dosage forms as well as other new drug delivery systems under investigation. POLYSSACHARIDES: Tamarind Gum: Tamarind xyloglucan is obtained from the endosperm of the seed of the tamarind tree, Tamarindus indica, a member of the 21 evergreen family . Tamarind Gum, also known as Tamarind Kernel Powder (TKP) is extracted from the seeds. The seeds are processed in to gum by seed selection, seed coat removal, separation, hammer milling, grinding and sieving. Tamarind gum is a polysaccharide composed of glucosyl : xylosyl : galactosyl in the ratio of 3:2:1 . Xyloglucan is a major structural polysaccharide in the primary cell walls of higher plants. Tamarind xyloglucan has a (1 4)--D-glucan backbone that is partially substituted at the O-6 position of its glucopyranosyl residues with -D-xylopyranose. Some of the xylose residues are -D-galactosylated at O-2 22. It is insoluble in organic solvents and dispersible in hot water to form a highly viscous gel such as a mucilaginous solution 23,24 with a broad pH tolerance and adhesivety . Tamarind gum is non Newtonian and yield higher viscosities than most starches at equivalent concentrations. This has led to its application as stabilizer, thickener, gelling agent and binder in food and pharmaceutical industries. In addition to these, other important properties of tamarind seed polysaccharide (TSP) have been identified recently. They include non25 26 carcinogenicity , mucoadhesivity, biocompatibility , high 27 24 drug holding capacity and high thermal stability . This has led to its application as excipient in hydrophilic drug delivery system 25-27. Magnetic microspheres of tamarind gum and chitosan were studied. The magnetic microspheres were prepared by suspension cross-linking technique. Microspheres formed were in the size range of 230 - 460 m. The magnetic material used in the preparation of the microspheres was prepared by precipitation from FeCl3 and FeSO4 solutionsin basic medium
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In another study Diclofenac sodium matrix tablets containing TSP was investigated. The tablets prepared by wet

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granulation technique were evaluated for its drug release characteristics. The result of this study demonstrated, that isolated TSP can be used as a drug release retardant. It was observed that the swelling index increased with the increase in concentration of TSP. Increase in polymer content resulted in a decrease in drug release from the tablets. The drug release was extended over a period of 12 hrs. and followed zero order kinetics 29. TSP was also examined for its sustained release property using both water soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble drugs 30 (indomethacin) . The release rates from the TPS matrix tablets were found to be dependent on the drug solubility. Zero order release was achieved for indomethacin from TSP. Mucoadhesive buccal patches using tamarind gum as mucoadhesive polymer for controlled release of benzydamine (BNZ) and lidocaine (LDC) were prepared and evaluated 31. A LDC-tannic acid complex was also prepared and tested. The patches, prepared by compressing appropriate mixtures containing the drug salts/complexes, lactose and tamarind gum, were tested in vitro for mucoadhesion and drug release, and in vivo on human volunteers for retention and release of BNZ. The devices containing the salts of BNZ with pectin and polyacrylic acid, and the complex of LDC with tannic acid showed zero-order release kinetics in vitro. The patches adhered for over 8 h to the upper gums of the volunteers, and were perfectly tolerated. BNZ hydrochloride was released in vivo and in vitro with practically identical profiles. Hibiscus rosasinensis: Hibiscus rosa-sinensis Linn of the Malvaceae family is also known as the shoe-flower plant, China rose, and Chinese 32,33 hibiscus . The fresh leaves of Hibiscus rosa-sinensis Linn are collected, washed with water to remove dirt and debris, and dried. The powdered leaves are soaked in water for 5-6 h, boiled for 30 min, and kept aside for 1 h for complete release of the mucilage into water. The material is squeezed from an eightfold muslin cloth bag to remove the marc from the solution. Acetone is added to the filtrate to precipitate the mucilage in a quantity of three times the volume of the total filtrate. The mucilage is separated, dried in an oven at a temperature < 50 C, collected, dried-powdered, passed through a sieve (number 80), and stored for further use in 34 desiccators . The plant contains cyclopropanoids, methyl sterculate, methyl-2-hydroxysterculate, 2-hydroxysterculate malvate,

and -rosasterol. Mucilage of Hibiscus rosa-sinensis contains L-rhamnose, D-galactose, D-galactouronic acid, and D35 glucuronic acid . The leaves are used in traditional medicines as emollients and aperients to treat burning sensations, skin 36 disease, and constipation . In a study the use of its mucilage for the development of 34 sustained release tablet has been reported . Matrix tablet containing dried mucilage and diclofenac sodium (DS) was prepared through direct compression techniques. It was found that mucilage can be used as release-retarding agent for 12 h when the drug-mucilage ratio was 1:1.5. Okra gum: Okra gum, obtained from the fruits of Hibiscus esculentus, is a polysaccharide consisting of D-galactose, L-rhamnose and L-galacturonic acid 37. Okra gum is used as a binder 38. In a study okra gum has been evaluated as a binder in 39 paracetamol tablet formulations . These formulations containing okra gum as a binder showed a faster onset and higher amount of plastic deformation than those containing gelatin. The crushing strength and disintegration times of the tablets increased with increased binder concentration while their friability decreased. Although gelatin produced tablets with higher crushing strength, okra gum produced tablets with longer disintegration times than those containing gelatin. It was finally concluded from the results that okra gum maybe a useful hydrophilic matrixing agent in sustained drug delivery devices. In another study Okra gum was evaluated as a controlledrelease agent in modified release matrices, in comparison with sodium carboxymethyl cellulose (NaCMC) and hydroxypropylmethyl cellulose (HPMC), using paracetamol as a model drug 40. Okra gum matrices provided controlledrelease of paracetamol for more than 6 h and the release rates followed time-independent kinetics. The release rates were dependent on the concentration of the drug present in the matrix. Okra gum compared favourably with NaCMC, and a combination of Okra gum and NaCMC, or on further addition of HPMC resulted in near zero order release of paracetamol from the matrix tablet. The results indicate that Okra gum matrices could be useful in the formulation of sustainedrelease tablets for up to 6 h. Guar gum: Guar gum comes from the endosperm of the seed of the legume plant Cyamopsis tetragonolobus. Guar gum is prepared by first drying the pods in sunlight, then manually

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separating from the seeds. The gum is commercially extracted from the seeds essentially by a mechanical process of roasting, differential attrition, sieving and polishing. The seeds are broken and the germ is separated from the endosperm. Two halves of the endosperm are obtained from each seed and are known as undehusked Guar Splits. Refined guar splits are obtained when the fine layer of fibrous material, which forms the husk, is removed and separated from the endosperm halves by polishing. The refined Guar Splits are then treated and finished into powders by a variety of routes and processing techniques depending upon the end product desired 41. Chemically, guar gum is a polysaccharide composed of the sugars galactose and mannose. The backbone is a linear chain of 1,4-linked mannose residues to which galactose residues are 1,6-linked at every second mannose, forming short sideFig. 1: Chemical structure of guar gum

thereby increasing drug release. A further increase in drug release was observed with rat caecal contents obtained after 7 days of pre-treatment. The presence of 4% w/v of caecal contents obtained after 3 days and 7 days of enzyme induction showed biphasic drug release curves. The results illustrate the usefulness of guar gum as a potential carrier for colon45 specific drug delivery . Locust bean gum: Locust Bean Gum (LBG) (also known as Carob Gum) is obtained form the refined endosperm of seeds from the carob tree Ceretonia Siliqua L. It is an evergreen tree of the legume family. Carob bean gum is obtained by removing and processing the endosperm from seeds of the carob tree. Processing of the ground endosperm is accomplished by dispersing the fine powder in boiling water and filtering to remove impurities. The gum is recovered by evaporating the 46 solution and tray or roll drying . Locust bean gum (LBG) is a plant seed galactomannan, composed of a 1-4 linked -D-mannan backbone with 1- 6-

Fig. 2: Chemical structure of locust bean gum

branches . Guar gum is more soluble than locust bean gum and is a better emulsifier as it has more galactose branch points. It degrades 43 at extremes of pH and temperature (e.g. pH 3 at 50C) . It remains stable in solution over pH range 5-7. Strong acids cause hydrolysis and loss of viscosity, and alkalies in strong concentration also tend to reduce viscosity. It is insoluble in most hydrocarbon solvents. Guar gum is used and investigated as a thickener in cosmetics, sauces, as an agent in ice cream that prevents ice crystals from forming and as a fat substitute that adds the "mouth feel" of fat and binder or as disintegrator in tablets. Besides being used as a matrix former for sustained release tablets guar gum has been investigated as a carrier for indomethacin for colon-specific drug delivery using in vitro 44 methods . Studies in pH 6.8 phosphate buffered saline (PBS) containing rat caecal contents have demonstrated the susceptibility of guar gum to the colonic bacterial enzyme action with consequent drug release. The pre-treatment of rats orally with 1 ml of 2% w/v aqueous dispersion of guar gum for 3 days induced enzymes specifically acting on guar gum

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linked -D-galactose side groups . This neutral polymer is only slightly soluble in cold water; it requires heat to achieve full hydration, solubilization and maximum viscosity .48 The physico-chemical properties of galactomannan are 49 strongly influenced by the galactose content . A controlled delivery system for propranolol hydrochloride (PPHCL) using the synergistic activity of LBG and xanthan gum (X) was studied. Granules of PPHCL were prepared by using different drug: gum ratios of X, LBG alone and a mixture of XLBG (X and LBG in 1: 1 ratios). The XLBG matrices exhibited precise controlled release than the X and LBG matrices because of burst effect and fast release in case of X and LBG alone respectively and there was no chemical interaction between drug and polymers in the XLBG formulation as conformed by FTIR studies. The first-pass 50 effect of PPHCL can be avoided by using this formulation .

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Isapgulla husk (Psyllium): Psyllium seed husks, also known as ispaghula, isabgol, or simply as psyllium, are portions of the seeds of the plant Plantago ovata, (genus plantago), a native of India and Pakistan. Gel forming fraction of the alkali-extractable polysaccharides is composed of arabinose, xylose and traces of other sugars. They are soluble in water, expanding and becoming mucilaginous when wet. Seeds are used commercially for the production of mucilage. It is white fibrous material, hydrophilic in nature and forms a clear colorless mucilaginous gel by absorbing water. Psyllium seed husk is 51 used as binder, disintegrant and release retardant . In an attempt, psyllium and acrylic acid based pH sensitive novel hydrogels using N, N0 methylenebisacrylamide (N, NMBAAm) as crosslinker and ammonium persulfate (APS) as initiator for model drugs (tetracycline hydrochloride, insulin and tyrosine), for the use in colon specific drug delivery was studied. The hydrogel was evaluated for the swelling mechanism and drug release mechanism from the polymeric networks. The effects of pH on the swelling kinetics and release pattern of drugs have been studied by varying the pH of the release medium. It has been observed that swelling and release of drugs from the hydrogels occurred through non-Fickian or anomalous diffusion mechanism in distilled water and pH 7.4 buffer. It shows that the rate of polymer chain relaxation and the rate of drug diffusion from these hydrogels are comparable 52. Sterculia foetida: Sterculia is a genus colloquially termed as tropical chestnuts, (Sterculia foetida). It contains a mixture of D-galactose, Lrhamnose and D-galactouronic acid. The galctouronic acid 48 units are the branching points of the molecule . In an independent investigation Sterculia foetida gum as a hydrophilic matrix polymer for controlled release preparation was evaluated. Different formulation aspects considered were: gum concentration (1040%), particle size (75420 m) and type of fillers. Tablets prepared with Sterculia foetida gum were compared with tablets prepared with Hydroxy methyl cellulose K15M. The release rate profiles were evaluated through different kinetic equations: zero-order, first-order, Higuchi, Hixon-Crowell and Korsemeyer and Peppas models. Suitable matrix release profile was obtained at 40% gum concentration. Higher sustained release profiles were obtained for Sterculia foetida gum particles in size range

of 76 125 m. The in vitro release profiles indicated that tablets prepared from Sterculia foetida gum had higher retarding capacity than tablets prepared with Hydroxy methyl 53 cellulose K15M prepared tablets . Honey locust gum: It is known botanically as Gleditsia triacanthos, and belongs to the order Leguminosea (suborder Mimoseae). The gum is obtained from the seeds of the plant. The seed contains proteins, fats, carbohydrates and fibers 54. Honey locust gum (HLG) was used to produce matrix tablets at different concentrations (5% and 10%) by wet granulation method 55. Theophylline was chosen as a model drug. The matrix tablets containing hydroxyethylcellulose and hydroxypropyl methylcellulose as sustaining polymers at the same concentrations were prepared and a commercial sustained release (CSR) tablet containing 200 mg theophylline was examined for HLG performance. No significant difference in in-vitro studies was found between CSR tablet and the matrix tablet containing 10% HLG. Tara Gum: Tara gum is obtained from the endosperm of seed of Caesalpinia spinosa, commonly known as tara. It is small tree of the family Leguminosae or Fabaceae. Tara gum is a white, nearly odorless powder. It is produced by separating and grinding the endosperm of the mature black color seeds56. The major component of the gum is a galactomannan polymer similar to the main components of guar and locust bean gums, consist of a linear main chain of (1-4)--Dmannopyranose units with -D-galactopyranose units attached by (1-6) linkages. The ratio of mannose to galactose in tara gum is 3:1. produce highly viscous solutions, even at 1% concentration. Tara gum requires heating to disrupt aggregation and full dissolution, whereas guar gum is soluble in cold water57. Tara gum is used as a thickening agent and stabilizer in a wide range of food applications around the world. The use of tara gum as a controlled release carrier in the formulation of gastro retentive controlled release tablets58 and emulsions59 for drugs like metformin hydrochloride, ciprofloxacin hydrochloride, nimodipine, nifedipine, carvedilol, clozapine has been claimed in patents. Khaya gum: Khaya gum is a polysaccharide obtained from the incised trunk of the tree Khaya grandifoliola (family Meliaceae). It is

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known to contain highly branched polysaccharides consisting of D galactose, L-rhamnose, D-galacturonic acid and 4-Omethyl-D-glucoronic acid 60. Khaya gum has been shown to be useful as a binding agent in tablet formulations. Khaya gum is a hydrophilic polymer and has been shown to possess emulsifying properties comparable with acacia gum. The fact that the gum is naturally available, inexpensive and non-toxic has also fostered the interest in developing the gum for pharmaceutical use. Further work has also shown its potential as a directly compressible matrix system in the formulation of 61 controlled release tablets . Khaya gum has been successfully evaluated as a controlled release agent in comparison with hydroxypropylmethylcellulose (HPMC) using paracetamol (water soluble) and indomethacin (water insoluble) as model drugs. Tablets were produced by direct compression and the in-vitro drug release was assessed in conditions mimicking the gastrointestinal system. Khaya gum matrices provided a controlled release of paracetamol for up to 5 h. The release of paracetamol from khaya gum matrices followed timeindependent kinetics and release rates were dependent on the concentration of the drug present in the matrix. A combination of khaya gum and HPMC gave zero-order time-independent 62 release kinetics . In another study Khaya and albizia gums were evaluated as compression coatings for target drug delivery to the colon using indomethacin and paracetamol as model drugs. The core tablets were compression-coated with 300 and 400 mg of khaya gum & albizia gum respectively and also a mixture of khaya and albizia gum (1:1). Drug release studies indicated that khaya and albizia gums were capable of protecting the core tablet in the physiological environment of the stomach and small intestine, with albizia gum showing greater ability than khaya gum. The release from tablets coated with the mixture of khaya and albizia gums was midway between the two individual gums, indicating that there was no interaction between the gums. Studies carried out using rat caecal matter in phosphate-buffered saline at pH 6.8 (simulated colonic fluid) showed that the gums were susceptible to degradation by the colonic bacterial enzymes, leading to release of the drug. The results demonstrate that khaya gum and albizia gum 61 have potential for drug targeting to the colon . Aloe Mucilage: Aloe mucilage is obtained from the leaves of Aloe barbadensis Miller. Many compounds with diverse structures have been isolated from both the central parenchyma tissue of

Aloe vera leaves and the exudate arising from the cells adjacent to the vascular bundles. The bitter yellow exudate contains 1,8 dihydroxyanthraquinone derivatives and their 63 glycosides . The aloe parenchyma tissue or pulp has been shown to contain proteins, lipids, amino acids, vitamins, enzymes, inorganic compounds and small organic compounds in addition to the different carbohydrates. Many investigators have identified partially acetylated mannan (or acemannan) as the primary polysaccharide of the gel, while others found pectic substance as the primary polysaccharide.
Fig. 3: Chemical structure of acemannan

Other polysaccharides such as arabinan, arabinorhamnogalactan, galactan, galactogalacturan, glucogalactomannan, galactoglucoarabinomannan and glucuronic acid containing polysaccharides have been 64 isolated from the Aloe vera inner leaf gel part . A. vera has been used for many centuries for its curative and therapeutic properties. In the pharmaceutical industry, it has been used for the manufacture of topical products such as ointments and gel preparations, as well as in the production of 65, 66 tablets and capsules . Important pharmaceutical properties that have been recently discovered for both the A. vera gel and whole leaf extract include the ability to improve the bioavailability of co-administered vitamins in human 67 subjects . Dried A. vera leaf gel (acetone precipitated component of the pulp) was directly compressed in different ratios with a model drug to form matrix type tablets, including ratios of 1:0.5, 1:1, 1:1.5 and 1:2. These matrix systems showed good swelling properties that increased with an increase of aloe gel concentration in the formulation. The directly compressed matrix type tablets also showed modified release behavior with 35.45% and 30.70% of the dose released during the first hour and the remaining of the dose was released over a 6 hour period for those formulations containing the lower ratios of gel to drug, namely 1:0.5 and 1:1. The formulation that contained the highest ratio of gel to drug, namely 1:2 exhibited only a 23.25% drug release during the first hour with the remaining of the dose being released over an 8 hour period. The dried A. vera gel polysaccharide component therefore showed excellent potential to be used as an excipient in the formulation of direct compressible sustainedrelease matrix type tablets 68.
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Hakea Gum: Hakea gum a dried exudate from the plant Hakea gibbosa family Proteaceae. Gum exudates from species have been shown to consist of L-arabinose and D-galactose linked as in gums that are acidic arabinogalactans (type A). Molar proportions (%) of sugar constituents Glucuronic acid, Galactose, Arabinose, Mannose, Xylose is 12:43:32:5:8. The 69 exuded gum is only partly soluble in water . Hakea gibbosa (Hakea) was investigated as a sustainedrelease and mucoadhesive component in buccal tablets. Tablet with drug chlorpheniramine maleate (CPM) with either sodium bicarbonate or tartaric acid in a 1:1.5 molar ratio and different amount of Hakea were formulated using a direct compression technique and were coated with hydrogenated castor oil (Cutina) on all but one face. The resulting plasma CPM concentration versus time profiles was determined following buccal application of the tablets in rabbits. The force of detachment for the mucoadhesive buccal tablets increased as the amount of Hakea gum was increased following application to excised intestinal mucosa. Addition of sodium bicarbonate or tartaric acid, as well as higher amounts of CPM, did not affect the mucoadhesive bond strength. These results demonstrate that the novel, natural gum, H. gibbosa, may not only be used to sustain the release 70 but can also act as bioadhesive polymer . Konjac glucomannan: Konjac glucomannan, which is extracted from the tubers of Amorphophallus konjac is a very promising polysaccharide for incorporation into drug delivery systems. The konjac glucomannan molecule consists of D-glucose and Dmannose linked by 13-1,4 linkage, and the ratio of mannose to glucose has been reported as 1.6:1, while there is some
Fig. 4: Chemical structure of konjac glucomannan

It was shown that konjac glucomannan (KGM) gel systems were able to maintain integrity and control the release of theophylline and diltiazem for 8 hours. The Japanese and European varieties of KGM synergistically interact with Xanthan gum (XG) giving rise to gel formation; the synergism being maximum at a 1:1 ratio. By contrast, the American KGM does not show such effect forming only viscous solutions. Drug diffusion coefficients of theophylline and diltiazem HCl, with different molecular size and net charge, were evaluated in systems containing KGM/XG in the ratio of 1:1. KGM/XG systems were more efficient than the XG alone for controlling drug diffusion of small molecules because of the gel formation 72. 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 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 73 effectively retard drug diffusion . Mimosa scabrella: Highly hydrophilic galactomannan is obtained from the seeds of Mimosa scabrella (a brazilian leguminous tree called bracatinga) of the Mimosaceae family. Its seeds provided 2030% of galactomannan (G) with a mannose: galactose ratio of 1.1:1. The galactomannan was obtained by first milling the seeds of M. scabrella followed by boiling in water for 10 min and then extracting from the aqueous phase for 4 h 0 under mechanical stirring at 30 C. The dispersion was filtered and the filtrate was precipitated with ethanol 50% (v/v). The precipitate was washed in a gradient of ethanol (70100% 74 v/v) and dried . In an independent study directly compressed theophylline tablets, containing commercial xanthan (X) (Keltrol) and a highly hydrophilic galactomannan (G) from the seeds of Mimosa scabrella as release-controlling agents, was studied. Gums were used at 4, 8, 12.5 and 25% (w/w), either alone or in mixture (X:G 1:1). The G obtained by different methods was vacuum oven dried (VO) or spray dried (SD), which were then evaluated for their in vitro drug release. The pH of the dissolution medium (1.4) was changed to 4.0 and 6.8 after 2 and 3 h, respectively. Tablets containing G (SD) resulted in more uniform drug release than G (VO) ones, due to their

branching at the C-3 of the mannose unit . Since konjac glucomannan by itself forms very weak gels, it has been investigated as an effective excipient in controlled release drug delivery devices in combination with other polymers or by modifying its chemical structure.

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smaller particle size. As the polymer concentration was increased the drug release decreased and all formulations at 25% w/w of gums showed excessive sustained release effect. The matrices made with alone X showed higher drug retention for all concentrations, compared with G matrices that released the drug too fast. The XG matrices were able to produce near zero-order drug release. The XG (SD) 8% of tablets provided the required release rate (about 90% at the end of 8 h), with zero-order release kinetics 74. Mimosa pudica: Mimosa pudica, commonly known as sensitive plant belongs to family Mimosaceae. Mucilage of M. pudica is obtained from seeds, which is composed of d-xylose and d-glucuronic acid. Mimosa seed mucilage hydrates and swells rapidly on coming in contact with water. Earlier the seed mucilage was evaluated for binding and disintegrating agent75. In a study of mucilage obtained from M. pudica as sustained release material was investigated. Matrix tablets containing different proportions of mucilage, dibasic calcium phosphate as diluent and diclofenac sodium as model drug was formulated by wet granulation method. The study reveals that the drug release from the matrix tablet decreases as the concentration of mucilage increased and followed Higuchi square root release kinetics. The drug release mechanism was mainly diffusion for tablets containing higher proportion of mucilage and a combination of matrix erosion and diffusion for tablets containing smaller proportion of mucilage. The study demonstrated that formulation containing mucilage to drug in the proportion of 1:40 was found to be similar to the 75 commercial sustained-release formulation of diclofenac . Hupu gum : Hupu gum or Gum kondagogu (GKG) is a naturally occurring polysaccharide derived as an exudate from the tree (Cochlospermum gossypium). Basically it is a polymer of
Fig. 5

uronic acid content, protein, tannin and soluble fibers 78. Gastric floating drug delivery system of Diltiazem HCl was studied using hupu gum as matrix forming polymer. Tablets were prepared by wet granulation method. Optimization study was carrier by three factor, three level Box-Behnken Design. The polymer concentration, % w/w of sodium bicarbonate and % w/w of pharmatose to the weight of drug and polymer were selected as independent variables. Cumulative percent drug released at 12 hrs was selected as dependent variable. The release rate decreased as the proportion of hupu gum increased. The results demonstrated that hupu gum is a suitable polymer for sustained release 79 gastric floating system . Albizia gum: Albizia gum is obtained from the incised trunk of the tree Albizia zygia, family Leguminosae and is shaped like round elongated tears of variable color ranging from yellow to dark brown. It consists of -1 3-linked D-galactose units with some 1-6-linked D-galactose units. The genus Albizzia containing some twenty-six species is a member of the Mimosaceae, a family which also includes the gum-bearing genera Acacia and Prosopis. Only two species of Albizia, A. zygia and A. sassa, are however, known to produce gum. Albizia gum has been investigated as a possible substitute for gum arabic as a natural emulsifier for food and 80,81 pharmaceuticals . These gums were tried as coating materials in compression-coated tablets, which degraded, by 62 the colonic microflora, thereby releasing the drug . Fenugreek: Trigonella Foenum-graceum, commonly known as Fenugreek, is an herbaceous plant of the leguminous family. Fenugreek seeds contain a high percentage of mucilage (a natural gummy substance present in the coatings of many seeds). Although it does not dissolve in water, mucilage forms a viscous tacky mass when exposed to fluids. Like other mucilage- containing substances, fenugreek seeds swell up 82 and become slick when they are exposed to fluids . The husk from the seeds is isolated by first reducing the size, then separated by suspending the size reduced seeds in chloroform for some time and then decanting. Successive extraction with chloroform removes the oily portion which is 83 then air dried . A different extraction procedure is also reported to isolate the mucilage from the husk. The powdered seeds are extracted with hexane then boiled in ethanol. The treated powder is then

rhamnose, galacturonic acid, glucuronic acid, b-D galactopyranose, a-D-glucose, b-D-glucose, galactose, arabinose, mannose and fructose with sugar linkage of (12) bD-Gal p, (16), b-D-Gal p, (14) b-D-Glc p, 4-0-Me-a-D-Glc p, 76,77 (12) a-L-Rha . Hupu gum is also composed of higher
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soaked in water and mechanically stirred and filtered. Filtrate is then centrifuged, concentrated in vacuum and mixed with 96% ethanol. This is then stored in refrigerator for 4 hrs to 84 precipitate the mucilage . The mucilage derived from the seeds of fenugreek, was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel K4M was used as a standard controlled release polymer for comparison purposes. A reduction in the release rate of propranolol hydrochloride was observed with increase in concentration of the mucilage in comparison to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug: mucilage ratio. Fenugreek mucilage at a concentration of about 66% w/w was found to be a better release retardant 84 compared to hypomellose at equivalent content . Lepidium sativum: In a different study a gel forming husk powder obtained from Lepidium sativum seeds was used to prepare solid controlled release oral unit dose pharmaceutical composition, comprising one or more of therapeutic agent/drug. The gel forming husk powder obtained from Lepidium stivum seeds is present in the range of 10 to 70 % of the total weight of dosage form, the cross-linking enhancer selected from xanthan gum, karaya gum and the like in amounts of between 3 to 10 % by weight of the dosage form to give a release profile between 4 to 20 hours. The total excipients present are 85 between 10 to 40 % by weight of the total dosage form . RESINS: Gum Copal: Gum copal (GC) is a natural resinous material of plant Bursera bipinnata (family Burseraceae).Copal, a resinous material, is obtained from the plants of araucariaceae and 86 caesalpinaceae, a subfamily of leguminoaceae . Copal resin (CR) contains agathic acid, a diterpenoid and related lobdane compounds along with cis-communic acid, trans-communic acid, polycommunic acid, sandaracopimaric acid, agathalic acid, monomethyl ester of agathalic acid, agatholic acid and acetoxy agatholic acid. CR obtained from leguminoaceae family contains copalic acid, pimaric acid, isopimaric acid, dehydro-dehydroabietic acid, dehydroabietic acid and abietic acid 86. Medicinally, Copal is used in the treatment of headache, 87 fever, burns and stomach ache . In dentistry, it is used as binding media in dental products and in treatment of micro
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leakage in teeth 88. Recently, Copal gum has been evaluated as matrix-forming material for sustaining the drug delivery 13. In an independent study copal resin was investigated as a film 89 forming agent . The free films, prepared in alcohol by solvent evaporation technique, were brittle with high tacking property. Addition of 1% w/w propylene glycol improved the mechanical properties of copal resin films, whereas glyceryl monostearate, sorbitan mono-oleate and sorbitan monolaurate in 15% w/w reduced the tackiness significantly. CR films showed good swelling property in phosphate buffer (pH 7.4). It was concluded that it can be used as a coating material for sustained release and colon-targeted drug delivery. Gum Damar: Gum damar (GD) is a whitish to yellowish natural gum of plant Shorea wiesneri (family Dipterocarpaceae). It contains about 40% alpha-resin (resin that dissolves in alcohol), 22% 13 beta resin, 23% dammarol acid and 2.5% water . It has been used for water-resistant coating and in pharmaceutical and dental industries for its strong binding 90 properties . In India, Sal damar has been widely utilized in 91 the indigenous system of medicine . Natural gum copal and gum damar as novel sustained release matrix forming materials in tablet formulation was evaluated. Matrix tablets were prepared by wet granulation technique using isopropyl alcohol as a granulating agent. Diclofenac sodium was used as a model drug. Effect of gum concentration (10, 20 and 30% w/w with respect to total tablet weight) on in vitro drug release profile was examined. Matrix tablets with 30% w/w gum copal and gum damar showed sustained drug delivery beyond 10 h. Drug release from gum copal matrix tablets followed zero order kinetics while gum damar (10 and 20% w/w) was found suitable to formulate the insoluble plastic matrix that releases the drug by diffusion. It was concluded that both gums possess substantial matrix forming property that could be used for sustained drug 13 delivery . TANNINS: Bhara Gum: Gum Bhara is a yellowish natural gum of plant Terminalia bellerica roxb. belonging to family Combretaceae. Bahera gum, extracted from the bark of Terminalia bellerica, is a 92 waste material . Main chemical constitutents are tannins which mainly include - sitosterol, gallic acid, ellagic acid, 93 ethyl gallate, galloyl glucose and chebulaginic acid .
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It has been mainly used as a demulcent and purgative. It is also used as an emulgent in cosmetic industries. Wide applications of bhara gum indicate their hydrophilic nature, 94 and compatibility with the physiologic environment . A new sustained release microencapsulated drug delivery 95 system employing bhara gum has been proposed . The microcapsules were formulated by ionic gelation technique using famotidine as the model drug. The effect of different drug: bhara gum ratio on in vitro drug release profile was examined and compared with guar gum. Remaining all parameters was constant. Microcapsules employing bhara gum exhibited slow release of famotidine over 10 hr. Fickian release was observed from most of the formulations with bhara gum. It was concluded that this gum possesses substantial release controlling properties that could be used for sustained drug delivery. OTHERS: Moi gum: The gum is obtained from Lannea coromandelica (Houtt.) Merrill (Anacardiaceae). Moi gum is yellowish white color in fresh and on drying becomes dark. Gum ducts are present in leaves, stems and fruits and are most abundant in the bark of 96 the stem . The roots contain cluytyl ferulate; heartwood gives lanosterol; bark, dlepi- catechin and (+)-leucocyanidin; flowers and leaves, ellagic acid, quercetin and quercetin-3 arabinoside. Flowers also contain iso-quercetin and morin. Leaves in addition contain beta-sitosterol, leucocyanidin and leucodelphinidin 97. Natural gum moi was successfully evaluated as microencapsulating agent and release rate controlling material for lamivudine. Microspheres were prepared by solvent evaporation technique. Effect of drug: gum ratio on in vitro drug release profile was investigated. The rate limiting capacity of moi gum was compared with guar gum as control by keeping all the parameters constant. The gum produced microspheres having satisfactory size (24-32m) and acceptable morphological properties. Microspheres of moi gum exhibited sustained action beyond 10 hr in comparison to guar gum but the combination of both the gums in 1:1 ratio demonstrated an additional sustained action 98. CONCLUSION The use of natural gums for pharmaceutical applications is attractive because they are economical, readily available, non-toxic, capable of chemical modifications, potentially
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biodegradable and with few exceptions, also biocompatible. Majority of investigations on natural polymers in drug delivery systems center around polysaccharides. Natural gums can also be modified to have tailor-made products for drug delivery systems and thus can compete with the synthetic controlled release excipients available in the market. Though the use of traditional gums has continued, newer gums have been used, some of them with exceptional qualities. Many other new gums viz. sesbenia gum, tara gum, etc. can be explored for their sustained release properties. These have found application not only in sustaining the release of the drugs but are also proving useful for development of gastro retentive dosage form, bioadhesive system, microcapsules etc.

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