|Natural Polymeric materials; Pharmaceutical excipients; Biodegradable; Eco-friendly
|Drugs are hardly administered as such but are almost always formulated into a suitable dosage form with the aid of excipients, which serve various functions such as binding, lubricating, gelling, suspending, flavoring, sweetening and bulking agent among others . The International Pharmaceutical Excipients Council defines excipients as substances, other than the active drug substances of finished dosage form, which have been appropriately evaluated for safety and are included in a drug delivery system to either aid the processing of the drug delivery system during its manufacture; protect, support orenhance stability, bioavailability, or patient acceptability; assist in product identification; or enhance any other attributes of the overall safety and effectiveness of the drug delivery system during storage or use . Excipients play a critical role in the creation of medicines, helping to preserve the efficacy, safety, and stability of active pharmaceutical ingredients (APIs) and ensuring that they deliver their promised benefits to the patients. Optimal use of excipients can provide pharmaceutical manufacturers with cost-savings in drug development, enhanced functionality and help in drug formulations innovation.
|Excipients are the largest components of any pharmaceutical formulation. They can be of natural or synthetic origin and synthetic excipients have become commonplace in today’s pharmaceutical dosage forms . It is common knowledge that both synthetic and semi-synthetic products have enjoyed a long history of use, frequently offering unique properties and advantages over naturally derived compounds, including a low sensitivity to various ingredients or moisture, resulting in more efficient and effective pharmaceutical products . But despite the many potential benefits of synthetic excipients, manufacturers must still address a number of challenges before their current universe of implementation can be expanded. The terms ‘synthetic’ and ‘semi-synthetics are both broadly used to distinguish this family of excipients from those extracted from natural sources. Semi-synthetic typically refers to a substance that is naturally derived but has been chemically modified. Most excipients in use today fall into this category and there must be the ‘natural’ to obtain the ‘semi-synthetic’ excipients. In contrast, ‘synthetic’ ‘is usually defined as a pure synthetic organic chemical that is derived from oil or rock .
|Lipids, carbohydrates and proteins are natural polymeric materials. Natural polysaccharides, as well as their derivatives, represent a group of polymers that are widely used in pharmaceutical formulations and in several cases their presence plays a fundamental role in determining the mechanism and rate of drug release from the dosage form. These naturally occurring polymers have been employed as excipients in the pharmaceutical industry in the formulation of solid, liquid and semisolid dosage forms in which they play different roles as disintegrates, binders, film formers, matrix formers or release modifiers, thickeners or viscosity enhancers, stabilizers, emulsifiers, suspending agents and muco adhesives [4,5]. Specifically, they have been used in the formulation and manufacture of solid monolithic matrix systems, implants, films, beads, micro particles, nanoparticles, inhalable and injectable systems as well as viscous liquid formulations [5-7].
|Their growing role and application in the pharmaceutical industry may be attributable not only to the fact that they are biodegradable and toxicologically harmless raw materials of low cost and relative abundance compared to their and synthetic counter parts [8,9], but also because natural resources are renewable and if cultivated or harvested in a sustainable manner, they can provide a constant supply of raw material . Furthermore, their extensive applications in drug delivery have been realized because as polymers, they offer unique properties which so far have not been attained by any other materials . They can be tailored for many applications based on the very large chains and functional groups which can be blended with other low- and high–molecular-weight materials to achieve new materials with various physicochemical properties. Consequently, many of the widely used excipients today are chemical modifications of the natural excipients to overcome some of their disadvantages.
|A couple of review articles on natural gums are available in literatures [12,13]. Some of the reviews covered the chemical structure,occurrence and production of exudate gums, their size and relative importance of the various players on the world market and focused on their application in food and other areas . Due to the growing interest in the use of natural polymeric materials as pharmaceutical excipients, as demonstrated by the number of published scientific papers, it is difficult to cover all that might be available in a single article. It is intended in this review to discuss the uses of natural polymers as excipients in pharmaceutical formulations. Specific mention is made of some of the natural products already in use as pharmaceutical excipients and those being researched for this purpose.
|Natural Polymeric Materials
|Natural polymers are obtained from different sources and this review will attempt to briefly discuss them according to their sources. Mention is made of those that are relevant to the current topic.
|Polysaccharides of the plant cell wall
|Natural polymers which have their origin from the plant cell wall mainly include cellulose, hemicelluloses and pectin.
|Cellulose: In higher plants, cellulose is an essential structural component and represents the most abundant organic polymer . Cellulose is a linear unbranched polysaccharide consisting of β-1, 4-linked D-glucose units and many parallel cellulose molecules which form crystalline micro fibrils. The crystalline micro fibrils are mechanically strong and highly resistant to enzymatic attack and are aligned with each other to provide structure to the cell wall . Cellulose is insoluble in water and indigestible by the human body. It is however digested by herbivores and termites. Cellulose obtained from fibrous materials such as wood and cotton can be mechanically disintegrated to produce powdered cellulose which has been used in the pharmaceutical industry as filler in tablets. High quality powdered cellulose when treated with hydrochloric acid produces microcrystalline cellulose which is preferred over powdered cellulose because it is more free-flowing containing non-fibrous particles. It is consequently employed as diluents or filler/binder in tablets for both granulation and direct compression processes . The molecular structure of cellulose is shown in Figure 1.
|The formation of derivatives of cellulose is made possible by the hydroxyl moieties on the D-glucopyranose units of the cellulose polymer to give a variety of derivatives. Cellulose derivatives can be made by etherification, esterification, cross-linking or graft copolymerization . Etherification yields derivatives such as hydroxyl-propyl-methylcellulose and carboxyl-methyl-cellulose, while esterification results in derivatives which include cellulose nitrate, cellulose acetate and cellulose acetate phthalate. These derivatives have found application in membrane controlled release systems such as enteric coating and the use of semi-permeable membranes in osmotic pump delivery systems. They have also enjoyed wide use and application in monolithic matrix systems. Extensive studies conducted on these derivatives have proven their ability to sustain the release of medicaments and most of these derivatives have been employed for this purpose [17,18].
|Hemicellulose: Bound to the surface of cellulose microfibrils are complex polysaccharides which themselves do not form micro fibrils. These bound polysaccharides are called hemicelluloses and include xyloglycans, xylans, mannans and glucomannans, and β-(1→3, 1→4)-glucans . They can be extracted from the plant cell wall with the aid of strong alkali.
|Hemicelluloses have β-(1→4)-linked backbones with an equatorial configuration. In contrast to cellulose which is crystalline and unbranched, hemicellulose is amorphous and branched. Although the xyloglycans have similar backbone as cellulose, they contain xylose branches on 3 out of every 4 glucose monomers, while the β-1,4-linked D-xylan backbone of arabinoxylan contains arabinose branches .
|Glucomannan is mainly a straight-chain hydrocolloidal polysaccharide of the mannan family with about 8% branching through β-(1→6)-glucosyl linkages. The component sugars are β-(1→4)- linked D-mannose and D-glucose in a ratio of 1.6:1 which may differ depending on the source . The component sugars may contain acetyl side branches on some of the backbone units which contribute to the solubility and swelling capacity of the glucomannans. The acetyl groups consequently enhance the solubility of the glucomannans as natural polysaccharides possessing the highest viscosity and waterholding capacity. Konjakglucomannan is the most commonly used type of glucomannan obtained by extraction from the tubers of Amorphophalluskonjac K. Koch (Fam. Ulmaceae). Konjacglucomannan has been investigated as an effective excipient in controlled release drug delivery devices in combination with other polymers or by modifying its chemical structure. Combination of konjacglucomannan and xanthan gum in matrix tablets has been shown to effectively retard drug release by stabilisation of the gel phase of the tablets by a network of intermolecular hydrogen bonds between the two polymers .
|Pectins: Pectins are non-starch, linear polysaccharides extracted from the plant cell walls. They are predominantly linear polymers of mainly (1–4)-linked D-galacturonic acid residues interrupted by 1,2- linked L-rhamnose residues with a few hundred to about one thousand building blocks per molecule (molecular structure is shown in Figure 2), corresponding to an average molecular weight of about 50, 000 to about 180,000 . Being soluble in water, pectin is not able to shield its drug load effectively during its passage through the stomach and small intestine. It was found that a coat of considerable thickness was required to protect the drug core in simulated in vivo conditions . Hence the focus was shifted to the development of less soluble derivatives of pectin which get degraded by the colonic micro flora. Calcium salts of pectin reduced their solubility by forming an eggbox configuration. To overcome the drawback of high solubility of pectin, mixed films of pectin with ethyl-cellulose were investigated as a coating material for colon-specific drug delivery. These films combined the colon specific degradation properties of pectin with the protective properties of the water insoluble ethyl cellulose .
|Polymeric hydrogels are widely used as controlled-release matrix tablets. Some researchers  investigated the high-methoxy-pectin for its potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies showed that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and type of pectin in the matrix tablets. A very low solubility pectin-derivative (pectinic acid, degree of methoxylation 4%) was found to be well suited as an excipient for pelletisation by extrusion/spheronisation. The capacity as an extrusion aid was found to be high. Formulations containing only 20% pectinic acid resulted in nearly spherical pellets. All pectinic acid pellets were mechanically stable. They possessed an aspect ratio of approximately 1.15–1.20 and released 30–60% of a low solubility model drug within 15 min in simulated gastric fluid (0.1M HCl) and intestinal fluid (phosphate buffer pH 6.8) .
|Micro particulate polymeric delivery systems have been reported as a possible approach to improve the low bioavailability characteristics observed in 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 piroxicameye drops.
|Investigation on the suitability of amidated pectin as a matrix patch for transdermal chloroquine delivery has been reported . This was in an effort to mask the bitter taste of chloroquine when orally administered. The results suggested that the pectin-chloroquine patch matrix preparation has potential applications for the transdermal delivery of chloroquine and perhaps in the management of malaria. Calcium pectinate nanoparticles to deliver insulin were prepared as a potential colonic delivery system by ionotropic gelation .
|In relation to cosmetics, using citronellal as a model compound, pectin gel formulations were evaluated for controlled fragrance release by kinetic and static methods. These formulations showed a prolonged duration of fragrance release and limitation of fragrance adsorption to the receptor skin layers. The increase in pectin concentrations suppressed the fragrance release by a diffusion mechanism, thereby proving that pectin/calcium micro particles are promising materials for controlled fragrance release . Drug delivery systems utilizing pectin is discussed by various researchers [30-35].
|Gums and mucilages
|Gums are natural plant hydrocolloids that may be classified as anionic or nonionic polysaccharides or salts of polysaccharides . They are translucent, amorphous substances usually produced by plants as a protective after injury. Gums, mucilage, pectins and celluloses are classified as substances that are condensations of pentoses and or hexoses. When gum is hydrolyzed, it yields large proportion of sugars and complex organic acid nucleus. It is by means of these organic acids that they do form salts with calcium or magnesium. According to Claus and Tyler  it is difficult to distinguish between gums and mucilage. In their opinion, one attempt is to refer to gums as water soluble and mucilage as water insoluble and the other approach is to refer to mucilage as pathological product and gums as physiological products.
|Gums and mucilage are produced in various ways by the plant. These substances can be formed from middle lamella as in the algae; cell wall as in the seed epidermis, seed endodermis, cells in the bark; special secretory cells as in the squill; in the schizogenous sacs as in the young stem of Rhamnuspurshiana, or by lysiogenous metamorphosis of the cell walls as in tragacanth and acacia .
|Gums have found pharmaceutical application since the early 1800 having gums like tragacanth, acacia, sterculia appearing in the United States Pharmacopoeia of 1820 and sodium alginate and agar in the 1947 National Formulary. The gums have been used as suspending agents for insoluble solids in mixtures, as emulsifying agents for oils and resins and as adhesive in pill and troche masses. Some gums are used as demulcent and emollient in hand lotion while others are used as protective colloid and as binding and disintegrating agents in tablet formulations .
|Google scholar entries on gums hit 7,500 in 2010 and were 8,260 a year later, showing the continuous interest in the use of these materials. There were 453 articles in the Wolter Kluwer’s database while in Pubmed the number was 7,979 scholarly articles on gums and mucilage, showing the importance of gums in pharmacy. It seems that gums and mucilage are the most highly investigated in the recent time as potential pharmaceutical excipients.
|Gums are naturally occurring components in plants, which are essentially cheap and plentiful. They have diverse applications as thickeners, emulsifiers, viscosifiers, sweeteners etc. in confectionary, and as binders and drug release modifiers in pharmaceutical dosage forms. However, most of the gums in their putative form are required in very high concentrations to successfully function as drug release modifiers in dosage forms due to their high swellability/ solubility at acidic pH. Hence, gums need to be modified to alter their physicochemical properties. For example, the modification of gums through derivatisation of functional groups, grafting with polymers, cross-linking with ions and other approaches as well as the factors influencing these processes in the pursuit of making them suitable for modifying the drug release properties of pharmaceutical dosage forms and for other purposes have been discussed with respect to optimization of their performance .
|Oral sustained release matrix tablets of water-insoluble drug, flurbiprofen was designed with natural gums and evaluated for the drug release characteristics using response surface methodology . The central composite design for two factors at five levels each was employed to systematically optimize drug release profile. In their work matrix tablets were prepared by direct compression technique. Xanthan and acacia gums were taken as the independent variables. Fourier transform infrared spectroscopy was employed to study the stability of drug used and the interactions between polymers and drug. Percent drug release in 2 and 8 hours were taken as response variables (Y1 and Y2, respectively). These workers found that the gums have significant effect on the drug release. Polynomial mathematical models, generated for the response variables using multiple linear regression analysis, were found to be statistically significant (P < 0.05).Contour plots were drawn to depict the relationship between response variables and independent variables. These workers concluded that the formulated matrix tablets followed zero-order kinetics with negligible drug release in 0.1N HCl at pH 1.2. Their objective of a formulation that would avoid the gastric effects of flurbiprofen was achieved. The mechanical and disintegration properties of paracetamol tablets formulated with Delonixregia seed gum (DRSG) as a binder have been studied . Tragacanth (TRG) and acacia (ACG) were used for comparison. Results showed that an increase in concentration of the binder increased the tensile strength while the brittle fracture index (BFI) was reduced. The crushing strength - friability/disintegration time ratio was ranked in the order: DRSG > ACG > TRG at 1%, w/w binder concentration. The ranking of high binder concentrations was ACG > TRG > DRSG. The results suggested that Delonixregia seed gum may be useful as a binder at low concentration and as sustained release matrix at high concentration. Another natural gum, damar was investigated as a novel micro encapsulating material for sustained drug delivery . Micro particles were prepared by oil-in-water emulsion solvent evaporation method employing ibuprofen and diltiazem hydrochloride as model drugs. Micro particles were evaluated for particle size, encapsulation efficiency and in vitro drug release kinetics. The effect of different gum: drug ratios and solubility of drug on micro particle properties was principally investigated. Gum damar produced discrete and spherical micro particles with both drugs. With a freely water soluble drug (diltiazem hydrochloride), gum damar produced bigger (45-50 μm) and rapid drug releasing micro particles with low encapsulation efficiencies (44-57%). Conversely, with a slightly watersoluble drug (ibuprofen), small (24-33 μm) micro particles with good encapsulation (85-91%) and sustained drug delivery were achieved. An increase in gum: drug ratio resulted in an increase in particle size and encapsulation efficiency but decreased the drug release rate in all cases. Drug release profiles of all micro particles followed zero order kinetics.
|Seaweed gums are typified by the carrageenans, agar and the alginates.
|Alginates: Alginates are natural polysaccharide polymers isolated from the brown sea weed (Phaeophyceae). Alginic acid can be converted into its salts, of which sodium alginate is the major form currently used. They are linear polymers consisting of D-mannuronic acid and L-guluronic acid residues arranged in blocks in the polymer chain. These homogeneous blocks (composed of either acid residue alone) are separated by blocks made of random or alternating units of mannuronic and guluronic acids. Alginates offer various applications in drug delivery, such as in matrix type alginate gel beads, in liposomes, in modulating gastrointestinal transit time, for local applications and to deliver the bio molecules in tissue engineering applications .
|Bio-adhesive sodium alginate microspheres of metoprolol tartarate for intranasal systemic delivery were prepared to avoid the first-pass effect, as an alternative therapy to injection, and to obtain improved therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres were prepared using emulsification-cross linking method. In vivo studies indicated significantly improved therapeutic efficacy of metoprolol from microspheres. There was sustained and controlled inhibition of isoprenaline-induced tachycardia as compared with oral and nasal administration of drug solution .
|A new insert, basically consisting of alginates with different hydroxyl-ethyl-cellulose content was developed to maintain a constant drug level over a certain period in the eye that was not possible with conventional eye drop application. This study showed good tolerance of the new calcium-alginate-insert applied to the ocular surface for controlled drug release . In order to achieve a 24h release profile of water soluble drugs, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The release of the drug from the sodium alginate formulation containing only xanthan gum was completed within 12h in the simulated intestinal fluid, while the drug release from the sodium alginate formulation containing only zinc acetate was completed within 2h in the same medium. Only the sodium alginate formulation, containing both xanthan gum and zinc acetate achieved a 24h release profile, either in the simulated intestinal fluid or in the pH change medium (pH 1.2). The helical structure and high viscosity of xanthan gum possibly prevented zinc ions from diffusing out of the ranitidine hydrochloride sodium alginate-xanthan gum-zinc acetate matrix so that zinc ions react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The crosslinking structure might control a highly water-soluble drug release for 24h .
|In a comparative study, alginate formulation appeared to be better than the poly-lactide-co-glycoside (PLG) formulation in improving the bioavailability of two clinically important antifungal drugs clotrimazole and econazole. The nanoparticles were prepared by the emulsion-solvent-evaporation technique in case of PLG and by the cation-induced controlled gelling in case of alginate .
|Carageenans: The carrageenans are sulphated marine hydrocolloids obtained by extraction from seaweeds of the class Rhodophyceae, represented by Chondruscrispus, Euchemaspinosum, Gigartinaskottsbergi, Gigartinastellata, Iradaealaminariodes. These are red seaweeds growing abundantly along the Atlantic coasts of North America, Europe and the western Pacific coast of Korea and Japan [45- 47]. Carrageenan is not assimilated by the human body. It provides only bulk but no nutrition. Carrageenan has been categorized into 3: kappa (κ), iota (ι) and lambda (λ). Lambda (λ-type) carrageenan produces viscous solutions but does not form gels. While the Kappa (κ-type) carrageenan forms a brittle gel, the iota (ι-type) carrageenan produces elastic gels . Studies have shown that the carrageenans are suitable in the formulation of controlled release tablets [49-51].
|Gum agar: Gum agar is extracted from the red-purple marine algae of the Rhodophyceae class. The species include Gelidiumcartilagineum and Gracilariaconfervoides which grow abundantly in the waters along the coast of Japan, New Zealand, South Africa, Southern California, Mexico, Chile, Morocco, and Portugal [46, 52, 53].
|Natural polysaccharide gums have also been obtained as carbohydrate fermentation products including Xanthan gum, produced in pure culture fermentation by the bacteria Xanthomonascampestris. It was originally obtained from the rutabaga plant . Gellan gum is a microbial polysaccharide obtained by fermentation by Pseudomonas elodea [53,54]. Pullulan is an extracellular homo-polysaccharide of glucose produced by many species of the fungus Aureobasidium, specifically A. pullulans.
|Xanthan gum: Xanthan gum, a complex microbial exopolysaccharide produced from glucose fermentation by Xanthomonas campestrispv. Campestris, a plant bacterium. It has a molecular weight of about 2 million . The gum consists of D-glucosyl, D-mannosyl, and D-glucuronyl acid residues in a molar ratio of 2:2:1. It also contains O-acetyl and pyruvyl residues in variable proportions . Xanthan gum is an acidic polysaccharide gum of penta-saccharide subunits. The penta-saccharide subunits form a cellulose backbone with trisaccharide side-chains.
|The applications of xanthan gum have been widely researched. It is non-toxic and has been approved by the Food and Drug Administration (FDA) for use as food additive without quantity limitations . Xanthan gum has been used in a wide range of industries including food, oil recovery, cosmetics and pharmaceutical industries. This wide application is due to its superior rheological properties. It is used as stabilizer for emulsions and suspensions. The gum forms highly viscous solutions which exhibit pseudoplasmic flow behavior . The literatures are littered with uses of xanthan as a pharmaceutical material [59-61].
|Gellan gum: DeacylatedGellan gum (Gellan) is an anionic microbial polysaccharide, secreted from Sphingomonas elodea, consisting of repeating tetrasaccharide units of glucose, glucuronic acid and rhamnose residues in a 2:1:1 ratio: [→3)–β–D–glucose–(1→4)– β–D–glucuronic acid–(1→4)– β–D–glucose–(1→4)–ᾳ–L–rhamnose– (1→]. In the native polymer two acyl substituents, L-glyceryl at O(2) and acetyl at O(6), are present on the 3-linked glucose. On average, there is one glyceryl per repeating unit and one acetyl for every two repeating units. DeacylatedGellan gum is obtained by alkali treatment of the native polysaccharide. Both native and deacylatedGellan gum are capable of physical gelation . To induce Gellan gelation it is necessary to warm up preliminarily a concentrated water solution of the polysaccharide: when the temperature is decreased, the chains undergo a conformational transition from random coilsto double helices (Coil-Helix Transition). Then a rearrangement of the double helices occurs leading to the formation of ordered junction zones (Sol- Gel Transition)  thus giving a thermo-reversible hydrogel . Much stronger physical thermo-reversible hydrogels are also obtained by addition of mono and divalent ions to Gellan solutions , or in acidic conditions .
|The physical gelation properties make this polysaccharide suitable as a structuring and gelling agent in food industries. Gellan is also exploited in the field of modified release of bioactive molecules. Aqueous solutions of Gellan are used as in situ gelling systems, mainly for ophthalmic preparation and for oral drug delivery . Physical Gellan hydrogels, prepared with mono or divalent cations, are used also for the preparation of tablets, beads  or microspheres. Interpenetrating polymer networks  or co-cross linked polymer networks  based on Gellan and other polysaccharide systems have also been developed as drug delivery matrices.
|Chemical hydrogels of Gellan are usually prepared via chemical cross linking of preformed physical networks, in order to enhance their mechanical properties, and to obtain slower drug release profiles. The aim of the present work was the development of a novel Gellan chemical hydrogel, with tunable physicochemical properties, obtained by cross linking the polymer chains with L-lysine ethyl ester moieties. As a first step, amidation of Gellan carboxyl groups in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxy-succinimide (NHS) was carried out it is well known that EDC and NHS have the ability to mediate the amide bond formation between amino and carboxyl groups. Ethyl ester of L-lysine (Lys) was used in order to protect the carboxyl group, thus avoiding the intermolecular reaction among the L-lysine molecules. Chemical hydrogels with different cross linking degrees were prepared, and their physico-chemical and rheological properties were studied and compared with the corresponding physical gels. The new networks, that were also investigated as matrices for modified oral release, using model molecules with different steric hindrance, can be proposed as carriers for the delivery of high molecular weight drugs such as proteins. Furthermore, the observed peculiar mechanical and rheological properties can be properly modulated in order to give matrices suitable for the depot systems [71,72].
|Pullulan: Insulin (Ins) spontaneously and easily complexed with the hydrogel nanoparticle of hydrophobized cholesterol-bearing pullulan (CHP) in water. The complexed nanoparticles (diameter 20–30 nm) thus obtained formed a very stable colloid. The thermal denaturation and subsequent aggregation of Ins were effectively suppressed upon complexation. The complexed Insulin was significantly protected from enzymatic degradation. Spontaneous dissociation of Insulin from the complex was barely observed, except in the presence of bovine serum albumin. The original physiological activity of complexed Insulin was preserved in vivo after i.v. injection . Figure 3 shows the microscopic view of pullulan in the solid and in the presence of water.
|Natural gums have also been obtained from animal sources. Examples include chitin and chitosan. Chitin is a structural polysaccharide which takes the place of cellulose in any species of lower plants and animals. It therefore occurs in fungi, yeast, green, brown and red algae and form the main component of the exoskeleton of insects and shells of crustaceans . Chitin is insoluble in water but when treated with strong alkali, it forms the water-soluble polysaccharide chitosan which is the only polysaccharide carrying a positive charge .
|Plants, which form the sources of exudate gums, when cut give a viscous, sticky fluid which exudes from the incision and tends to cover and seal the opening. Gum exudates are therefore believed to be produced by plants in order to seal-off infected sections of the plant and prevent loss of moisture due to physical injury or fungal attack . The fluid eventually dries to a brittle, translucent, glassy, hard mass. These gum exudates are secreted by various organs of the plant. They include tragacanth gum and acacia gum or gum Arabic.
|Acacia gum: Acacia gum or gum Arabic is the dried gummy exudate from the stems and branches of Acacia Senegal (Fam. Leguminosae) and other related African species of acacia [74,75]. Gum arabic is a branched molecule of 1, 3-linked β-Dgalactopyranosyl units. It consists of monosaccharide sugarss such as arabinose, glucuronic acid and rhamnose. Studies recorded success with gum Arabic as a matrix microencapsulating agent for the enzyme, endoglucanase . In this study gum Arabic was shown to give slow release endogucanase from the formulation. In another study gum arabic was used as an osmotic suspending and expanding agent to prepare monolithic osmotic tablet systems . There was zero order release of the active for up to 12 hours at a pH of 6.8. Heterogeneity of Acacia senegal gum by sodium sulfate –induced precipitation has been studied .
|Tragacanth gum: Gum tragacanth is a branched, heterogeneous, and anionic carbohydrate which consists of two major fractions: tragacanthin (water-soluble) and bassorin (water-swellable) . It is not understood yet if the two polysaccharides are in a physical mixture or chemically bonded to each other, although easy separation procedures favor the former hypothesis. Bassorin and tragacanthin composition differ particularly in terms of their uronic acid and methoxyl content ; it has been suggested that bassorin is a complex structure of polymethoxylated acids and on demethoxylation, probably yields tragacanthin . Gum tragacanth has been known and used for thousands of years. It is defined by the Food Chemical Codex as the dried gummy exudation obtained from different species of Astragalus (fam. Leguminosae) . It has been classified as generally recognized as safe at the 0.2–1.3% level in food stuffs in the USA since 1961 and has the number E413 in the list of additives approved by the Scientific Committee for Food of the European Community. The capacity of gum tragacanth to extensively modify the rheology of aqueous media even at fairly low concentration is the most important factor in evaluating tragacanth and is regarded as a measure of its quality and also a guide to its behavior as a suspending agent, stabilizer, and emulsifier . A few studies have been devoted to functional properties of gum tragacanth, and most of the works on structural and functional properties of the gum as well as its application in various fields have been done. Recently the flow behavior of six species of Iranian gum tragacanth dispersions was investigated at different temperatures and ionic strengths, within a concentration range (0.05–1.5% w/w) using a controlled shear rate rheometer. The steady shear measurements showed that all of the gum dispersions had shear-thinning natures. The power law model was used to describe the rheological properties of dispersions and Arrhenius model was used to evaluate the temperature effect. The workers carried out composition analysis; surface tension measurement, particle size analysis, and color measurement of all the species were also carried out. Their results indicated that the six species of gum tragacanth studied exhibited significantly different physicochemical properties .
|Mucilage gums: Many seeds contain polysaccharide food reserves which produce intracellular seed gums usually obtained by extraction from the seeds. Guar gum is obtained from the ground endosperms or seeds of the plant Cyamopsistetragonolobus (Fam. Leguminosae). Locust bean gum is obtained from the endosperms of the hard seeds of the locust bean tree (Carob tree), Ceratoniasiliqua (Fam. Caesalpiniaceae) .
|Locust bean gum: It is also called carob gum, as it is derived from the seeds of the leguminous plant carob, Ceratoniasiliqua Linn (Fam. Caesalpiniaceae). Locust bean gum has an irregularly shaped molecule with branched β-1, 4-D-galactomannan units (See Figure 4 for molecular structure). This neutral polymer is only slightly soluble in cold water; it requires heat to achieve full hydration and maximum viscosity. Cross-linked galactomannan however led to water-insoluble film forming product-showing degradation in colonic microflora The colon-specific drug delivery systems based on polysaccharides, locust bean gum and chitosan in the ratio of 2:3, 3:2 and 4:1, were evaluated using in vitro and in vivo methods Core tablets containing mesalazine with average weight of 80mg were prepared by compressing the materials using 6-mm round, flat, and plain punches on a single station tablet machine. The formulated core tablets were compression coated with different quantities of locust bean gum and chitosan. The in vitro studies in pH 6.8 phosphate buffer containing 2%w/v rat caecal contents showed that the cumulative percentage release of mesalazine after 26 hr was 31.25 ± 0.56, 46.25 ± 0.96, and 97.5 ± 0.26, respectively. The in vivo studies conducted in nine healthy male human volunteers for the various formulations showed that the drug release was initiated only after 5hr, which is the transit time of small intestine. In vitro drug release studies and in vivo studies revealed that the locust bean gum and chitosan as a coating material applied over the core tablet was capable of protecting the drug from being released in the physiological environment of stomach and small intestine and was susceptible to colonic bacterial enzymatic actions with resultant drug release in the colon (Figure 4).
|Guar gum: Guar gum, obtained from the ground endosperms of Cyamposistetragonolobus, consists of chiefly high molecular weight hydrocolloidal polysaccharide, composed of galactan and mannan units combined through glycosidic linkages and shows degradation in the large intestine due the presence of microbial enzymes. The structure of guar gum is a linear chain of β-D-mannopyranosyl units linked (1→4) with single member α-D-galacto-pyranosyl units occurring as side branches. It contains about 80% galactomannan, 12% water, 5% protein, 2% acid soluble ash, and 0.7% fat. Guar gum has a molecular weight of approximately 1 million, giving it a high viscosity in solution. This galactomannan is soluble in cold water, hydrating quickly to produce viscous pseudo plastic solutions that although shear-thinning generally have greater low-shear viscosity than other hydrocolloids. This gelling property retards release of the drug from the dosage form, and it is susceptible to degradation in the colonic environment.
|Guar gum is a non-ionic polysaccharide that is found abundantly in nature and has many properties desirable for drug delivery applications. However, due to its high swelling characteristics in aqueous solution, the use of guar gum as delivery carriers is limited. Guar gum can be modified by derivatization, grafting and network formation to improve its property profile for a wide spectrum of biomedical applications. Guar gum and its derivatives in various forms such as coatings, matrix tablets, hydrogels and nano/micro particles can be exploited as potential carriers for targeted drug delivery . An oral controlled drug delivery systems for highly water-soluble metroprolol using guar gum (30 (M1), 40 (M2) or 50% (M3) as a carrier in the form of a three-layer matrix tablet was formulated by wet granulation technique using starch paste as a binder. Three-layer matrix tablets of metoprolol tartrate were prepared by compressing on both sides of guar gum matrix tablet granules of metoprolol tartrate M1, M2 or M3 with either 50 (TL1M1, TL1M2 or TL1M3) or 75 mg (TL2M1, TL2M2 or TL2M3) of guar gum granules as release retardant layers. Both the matrix and three-layer matrix tablets were evaluated for hardness, thickness, drug content uniformity, and subjected to in vitro drug release studies. The amount of metoprolol tartrate released from the matrix and threelayer matrix tablets at different time intervals was estimated by using a HPLC method. Matrix tablets of metoprolol tartrate were unable to provide the required drug release rate. However, the three-layer guar gum matrix tablets (TL2M3) provided the required release rate on par with the theoretical release rate for metoprolol tartrate formulations meant for twice daily administration. The three-layer guar gum matrix tablet (TL2M3) showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40°C/75% RH for 6 months. The FT-IR study did not show any possibility of metoprolol tartrate/guar gum interaction with the formulation excipients used in the study. The results indicated that guar gum, in the form of threelayer matrix tablets, is a potential carrier in the design of oral controlled drug delivery systems for highly water-soluble drugs such as metoprolol tartrate . Similar results was obtained with guar gum at 65,75, and 85% in a three layer tablet of tri-metazidinedihydrochloride controlled release formulation .
|A novel tablet formulation for oral administration using guar gum as the carrier and indo-methacin as a model drug has been investigated for colon-specific drug delivery using in vitro methods. Drug release studies under conditions mimicking mouth to colon transit have shown that guar gum protects the drug from being released completely in the physiological environment of stomach and small intestine. Studies in pH 6.8 phosphate buffered saline (PBS) containing rat caecal contents have demonstrated the susceptibility of guar gum to the colonic bacterial enzyme action with consequent drug release. The pre-treatment of rats orally with 1 ml of 2% w/v aqueous dispersion of guar gum for 3 days induced enzymes specifically acting on guar gum thereby increasing drug release. A further increase in drug release was observed with rat caecal contents obtained after 7 days of pretreatment. 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 illustrated the usefulness of guar gum as a potential carrier for colon-specific drug delivery. The scientists concluded on the study that the use of 4% w/v of rat caecal contents in PBS, obtained after 7 days of enzyme induction provided the best conditions for in vitro evaluation of guar gum . Poly-acryl-amide-grafted-guar gum (pAAm-g-GG) was prepared by taking three different ratios of guar gum to acrylamide (1:2, 1:3.5 and 1:5). Amide groups of these grafted copolymers were converted into carboxylic functional groups. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry were used to characterize copolymers. Tablets were prepared by incorporating an antihypertensive drug viz., diltiazem hydrochloride. In-vitro drug release was carried out in simulated gastric and intestinal conditions. Effect of drug loading on release kinetics was evaluated. Release continued up to 8 and 12 h, respectively, for pAAm-g-GG and hydrolyzed pAAm-g-GG copolymers. Nature of drug transport through the polymer matrices was studied by comparing with Higuchi, Hixson-Crowell and Kopcha equations. The researchers found out that the drug release dissolution-controlled in case of unhydrolyzed copolymer while in the hydrolyzed copolymers, drug release was swelling-controlled initially (i.e., in 0.1N HCl), but at later stage, it became dissolution-controlled in pH 7.4. These observations led to the conclusion that Hydrolyzed pAAm-g-GG matrices are pH sensitive , which positioned them as potential materials for intestinal drug delivery .
|Grewia gum: Grewia genus is today placed by most authors in the Family Malvaceae, in the expanded sense as proposed in the Angiosperm Phylogeny Group (APG). Formerly it was placed in either the linden Family (Tiliaceae) or the Spermamanniaceae. However, these were both not monophylectic with respect to other Malvales. Grewia and similar genera have been merged into the Malvaceae. Together with the bulk of the former spermanniaceae, Grewia is in the Family Grewiodeae and therein the tribe Grewieae, of which it is the type genus .
|The genus was named by the father of modern taxonomy, Carolus Linnaeus (1707-1778), in honor of the Nehemiah Grew (1641-1712). Grew, from England, was one of the leading plant anatomists and microscope researchers of his time, and his study of pollen laid the groundwork for modern-day palynology . Briefly, Carl Linnaeus (Latinized as Carolus Linnaeus, also known after his ennoblement as Carl von Linne  who lived from 23 May 1707 – 10 January 1778) was a Swedish botanist, physician, and zoologist, who laid the foundations for the modern scheme of binomial nomenclature. He is known as the father of modern taxonomy, and is also considered one of the fathers of modern ecology . About 150 species of Grewia have been confined and most of them were said to be in Africa -.
|There were ten (10) citations in International Pharmaceutical Abstracts (IPA) database on grewia Family a year ago, in EBSCO there are thirty-six (36) while in PubMed there were thirty-eight (38) citations in 2010 on Grewia.
|Increased interest on Grewia mollisas a potential pharmaceutical excipient has been on since the last decade and has been investigated for its phytochemical, toxicological and histopathological properties . In their work they used soxhlet extraction to obtain the crude materials from the stem bark of the plants along with those of Boswelliadalziellii, paarophacurcas and Pterocarpuserinaceus claimed to be of medicinal values in Nigeria. The study showed that tannins, saponins, flavonoids, glycosides, balsam, phenols, terpenes, steroids were present while alkaloids were absent. The study further demonstrated that the plant is safe for human consumption with LD 50 of 1500 mg/kg body weight. The extracts showed no structural effects on the liver and heart.
|The actual investigation on the pharmaceutical uses of Grewia mollis was documented in the early 2000’s [93-98]. The scientists investigated some physicochemical and rheological characteristics as well as water vapor permeability of the aqueous-based films. The gum was investigated for its binding properties in sodium salicylate tablets  and the effect of granulating fluid on the release profile of drug containing the gum . Other workers  also found that method of incorporating the gum into tablet formulation had effect on tablet properties, where they discovered that incorporation by activation with water produced better tablet properties than when incorporate by wet granulation or direct compression. Scientists  evaluated the gum by acid treatment, heating and some modification showed reduced viscosity and improved drug release from tablets. More recently other researchers  investigated the binding property of the gum in comparison with both untreated gum and gelatin in paracetamol tablet formulations. Compression properties of the formulations were analyzed using density measurements and assessed by compression equation of Heckel. The mechanical properties of the formulations were assessed using crushing strength and friability as well as crushing strength friability ratio. The drug release properties of the tablets formed were assessed using disintegration and dissolution times. Tablet formulations containing treated grewia gum exhibited low onset of plastic deformation, while that of untreated gum and gelatin were relatively high onset of deformation. The friability of paracetamol tablet formulation increased with increase in acid concentration and treatment time. The crushing strength, disintegration and dissolution times decreased with increase in acid concentration and treatment time. Tablets containing untreated gum possessed high crushing strength, disintegration and dissolution times and low friability compared to those containing gelatin and the treated gum. Depending on the desired onset of action of medicament acid treated grewia gum can be used in formulation of conventional tablets especially if the formulation does not require sustained release . Advancement in technology and analytical tools will continue to aid the understanding of natural polymers and better position them for use as pharmaceutical excipients. Grewia gum was extracted from the inner stem bark of Grewia mollis and characterized by several techniques such as gas chromatography (GC), gel permeation chromatography (GPC), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermo gravimetric analysis of the extracted sample. Spectroscopic techniques such as x-ray photoelectron spectroscopy (XPS), Fouriertransformed infrared (FT-IR), solid-state nuclear magnetic resonance (NMR), and 1H and 13C NMR and NIR techniques were also used to characterize the gum [103,104]. The gum is a typically amorphous polysaccharide gum containing glucose, rhamnose, galactose, arabinose and xylose as neutral sugars. It has an average molecular weight of 5925 kDa expressed as the pullulan equivalent. The gum slowly hydrated in water, dispersing and swelling to form a highly viscous dispersion exhibiting pseudo plastic flow behavior. Fractions of the gum obtained by centrifugation successively at 4500 rpm for 30 minutes with average molecular weights between 230 and 235 kDa showed improved aqueous solubility that was useful in delivering more solids to the substrate when used as a film coating agent .
|Okra gum: Okra is a tall erect annual plant botanically known as Abelmoschusesculentus (Fam. Malvaceae). It is widely cultivated and grown in most tropical part of Nigeria. Okra has been used as food and soup in Africa  and Asia  and has been a subject of research in agriculture and food [105,107-119]. Okra is known for its viscous mucilaginous solution which results when it is crushed and extracted in water . The potential of okra gum as a pharmaceutical excipient has received attention in literatures as a binder [121,122], control release , film coating , bio-adhesive  and suspending [126-128] agent. Okra gum has been evaluated as a controlled-release agent in modified release matrices, in comparison with sodium carboxymethyl- cellulose (NaCMC) and hydroxyl-propyl-methyl-cellulose (HPMC), using Paracetamol as a model drug. Tablets were produced by direct compression and the in-vitro drug release was assessed in conditions mimicking the gastro intestinal system, for 6 h. Okra gum matrices provided a controlled-release of Paracetamol for more than 6 h and the release rates followed time-independent kinetics. The release rates were dependent on the concentration of the drug present in the matrix. The addition of tablet excipients, lactose and Avicel, altered the dissolution profile and the release kinetics. Okra gum compared favorably 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 indicated that Okra gum matrices was useful in the formulation of sustained-release tablets for up to 6h .
|Kyaha gum: Khaya gum is obtained by extraction from Khayasenegalensis and Khayagrandifoliola (Fam. Meliaceae). The comparative binding effects of khaya gum obtained from Khayasenegalensis and Khayagrandifoliola in paracetamol tablet formulation were evaluated . The mechanical properties of the tablets were assessed using the tensile strength (T), brittle fracture index (BFI) and friability (F) of the tablets while the drug release properties were assessed using disintegration and dissolution times. The tensile strength, disintegration and the dissolution times of tablets increased with the increase in binder concentration while F and BFI decreased.K. senegalensis gum produced strong tablets with long disintegration and dissolution times compared to K. grandifoliola gum. The results showed that K. senegalensis will be more appropriate as a binding agent than K. grandifoliola when high mechanical strength and slow release profiles of tablets are desired.
|Moringaoleifer gum: A natural gum obtained from plant Moringaoleifera gum was extracted by using water as solvent and precipitated using acetone as non-solvent. Physical characteristics such as, solubility, swelling index, loss on drying, and pH were studied. Diclofenac sodium was used as model drug for the formulation of gels. Seven batches of drug loaded gels with concentration of mucilage ranging from 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, and 8.5 were formulated by using glycerin as plasticizer and methyl paraben as preservative. The pH, viscosity, and in vitro diffusion profiles were studied. The gels prepared with 8.0% of mucilage were found to be ideal and comparable with a commercial preparation .
|Irvingiagabonensis: Irvingiagabonensis (AubryLecomte ex O’Rorke) Baill. Commonly known as ‘African mango’ or ‘bush mango’ is a tree of 15-40 m, with a bole slightly buttressed [132-135]. The plant is a wild forest tree [134,136] with dark green foliage and yellow fragrant flowers and occurs in the wild lowland forest; 2-3 trees occur together and in some areas, it is reported to be widespread. I.gabonensis is largely distributed in Africa [137-140]. The fruit is spherical with smooth yellow fibrous mesocarp and hard endocarp when ripe. The seed from the plant has been of interest in the food [136,141-143], beverages [144-146], medical [135,147-152] and pharmaceutical [153-162] as well as cosmetic circles . The seed of the plant contains lipids and polymeric constituents [105,137,146,164-167]. Both the lipids (dika fat) and the polymeric (gum) components are of importance to the pharmaceutical scientists as excipients in Africa and the developing world. The mucilage from the kernel has been used as binding agent in tablet formulation , as emulsifying and suspending agent [105,168]. On the other hand, the lipid has been employed in tableting as lubricant [162,169], sustained release ingredient [154,155,170], microencapsulation , as suppository base [158,159,172] and as a component of film coating operation . The lipids component of I.gabonensis seeds have been traditionally extracted using n-hexane  or other organic solvents ; and more recently an enzymatic approaches for extracting the lipid components have been investigated . The polymeric component of the seed has been extracted from aqueous dispersion using petroleum ether  or diethyl ether . None of the extraction processes described in the literature provided for simultaneous extraction of the lipid and polymer component until recently . This was to overcome adverse environmental consequences of disposal of organic solvents used in its extraction and also address worker’s safety concerns and cost of extraction. A lot have appeared in literature on the application of both the gum and the fat from this plant. The mucilage extracted from the kernels of Irvingiagabonensis was evaluated for use as suspending and emulsifying agent . The rheological behavior of the mucilage was studied and compared to that of tragacanth. As a suspending agent, Irvingia mucilage was compared to tragacanth at various concentrations (0.5, 1.0, 1.5 and 2.0% w/v) in the formulation of sulphanilamide suspensions. At all concentrations the formulated suspensions with Irvingia mucilage gave higher Hu (final sedimentation height) and F (sedimentation volume) values. As an emulsifying agent, the properties of Irvingia mucilage was compared to tragacanth and acacia gum. The emulsions prepared with 0.6, 1.0, and 1.5% tragacanth and Irvingia ‘cracked’ within six days while that with 12.5% w/v acacia started showing signs of creaming at the tenth day. The emulsion prepared with 2.0% w/v Irvingia mucilage was however stable throughout the six weeks of study. The results indicate that Irvingia mucilage performed better than acacia and tragacanth even at lower concentrations in the formulation of emulsions and suspensions.
|The potential of irvingia fat as a suppository base has been evaluated [158,172]. The binding effects on metronidazole tablets , sustained release profiles on some tablets [154,155] as well as lubricating potential in tablet formulations  incorporating irvingia gum have been studied.
|Hakeagibbosa gum: The muco adhesive and sustained-release properties of the water-soluble gum obtained from Hakeagibbosa (hakea), for the formulation of buccal tablets. Flat-faced tablets containing hakea were formulated using chlorpheniramine maleate (CPM) as a model drug had been investigated . In the study two types of tablets were prepared: uncoated tablets (type I) and tablets in which all but one face of the type I tablet was coated with hydrogenated castor oil (Cutina) using a compression coating technique (type II). FTIR, differential scanning calorimetry (DSC), UV spectroscopy, and acid–base titrations were used to evaluate the properties of the formulations. Mathematical modeling of the CPM release data was developed to elucidate the mechanism of drug release. The muco adhesive strength was evaluated by quantitating the force of detachment. Finally, the rates of water uptake and erosion were determined for the buccal tablets. The time required for 90% of the CPM to be released in vitro (t90%) was used as a basis for comparison. For formulations that did not contain hakea, the t90% was 14min for both directly compressed and wet granulated tablets, whereas the t90% for wet granulated tablets containing 2 or 32mg hakea/tablet was 36 and 165min, respectively. Directly compressed tablets containing 2, 12, 22, and 32mg hakea/tablet displayed t90% values of 48, 120, 330, and 405min, respectively. DSC, FTIR, UV spectroscopy and acid–base titration experiments suggested the absence of chemical interactions. The force of detachment for directly compressed and wet granulated tablets increased from 0.70 ± 0.3 to 4.08 ± 0.52 N and from 0.65 ± 0.28 to 3.94 ± 0.31 N as the amount of hakea per tablet was increased from 0 to 32 mg, respectively, at a 5 N attachment compression force. The workers concluded that hakea, may not only be utilized to sustain the release of CPM from a unidirectional-release buccal tablet, but it also exhibited excellent mucoadhesive properties. The mechanism by which CPM release was sustained was more likely due to slow relaxation of the hydrated hakea.
|Psyllium mucilage: Psyllium mucilage is obtained from the seed coat of Plantagoovata (Fam. Plantaginaceae) by milling the outer layer of the seeds . Psyllium has been evaluated for its tablet binding properties . Hydrogels of psyllium and methacrylamide prepared using N,N’-methylene-bis-acryl-amide as cross-linker and loaded with insulin showed controlled release of the active ingredient .
|Other natural gums and mucilage: Sterculiafoetida gum has been investigated as a swelling and erosion modulator in controlled release matrix tablets of diltiazem hydrochloride . The pharmaceutical uses of other gums have been explored. These include Colocassiaesculenta , seeds of Linumusitatissimum , malva nut gum .
|Inulin is a naturally occurring storage polysaccharide found in many plants such as onion, garlic, artichoke, and chicory. Chemically, it belongs to the gluco-fructans and consists of a mixture of oligomers and polymers containing 2 to 60 (or more) β-2-1 linked D-fructose molecules. Most of these fructose chains have a glucose unit as the initial moiety. The inulin has been incorporated into Eudragit RS films for preparation of mixed films that resisted degradation in the upper GIT but digested in human fecal medium by the action of Bifidobacteria and Bacteroids . Various inulin hydrogels have been developed that serve as potential carriers for the introduction of drugs into the colon . Vinyl groups were introduced in inulin chains to form hydrogels by free radical polymerization. Inulin was reacted with glycidylmethacrylated in N,N-dimethylformamide in the presence of 4-dimethylaminopyridine as catalyst. 1H and 13C NMR spectroscopy were used for the characterization of the obtained reaction product and revealed the conversion of the incorporated vinyl groups into covalent crosslink’s upon free radical polymerization of aqueous solutions of the derivatized inulin .
|Starch whether in the native or modified form has been used as one of the key pharmaceutical excipients in pharmaceutical tablet and capsule formulations. It serves various functions such as bulking, binder, disintegrant or aiding drug delivery. Microcapsules containing a protein and a proteinase inhibitor were prepared to deliver proteins or peptidic drugs orally . Starch/bovine serum albumin mixedwalled microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride. The microcapsules were loaded with native or amino-protected aprotinin by incorporating protease inhibitors in the aqueous phase during the cross-linking process. The protective effect of microcapsules with aprotinin for bovine serum albumin was revealed in vitro.
|Acetylation of starch considerably decreases its swelling and enzymatic degradation . Starch-acetate (SA) based delivery systems for controlled drug delivery has been reported . These workers reported that acetylated of potato starch substantially retard drug release compared to that of natural potato starch film.
|Tablet film coating with amylose-rich maize starch has been investigated . These workers carried out a study on the use of aqueous –based amylose-rich starch (Hylon VII™) film coating of the tablets. Using a side vented pan coating system, they investigated the influence of plasticizer concentration, temperature of coating pan and the spray rate of the coating solution. In their study they observed that at low spray rates, the temperature of the coating pan did not affect the roughness of the coated tablet but at high spray rates, high temperatures gave smooth films. The dissolution rate of all Hylon VII™ –coated tablets was rapid in an acid medium, releasing 75% of the drug. Other works on the use of amylose and native starches as film forming agent in pharmaceutical film coatings have been reported [189-192]. A combination of amylose and ethyl-cellulose aqueous and non-aqueous based coatings for colon drug delivery has been reported [189-191,193]. Some workers  sourced and obtained cellulose and microcrystalline cellulose from maize cobs and they compared the tablet properties of paracetamol tablets made by direct compression with microcrystalline cellulose (MCC) as sole excipients with a multiexcipient formula in wet granulation and found that the former possesses better tablet properties apart from the added advantages of direct compression and fewer ingredients. Scientists have evaluated the physicochemical and powder properties of alpha- and microcrystalline cellulose derived from maize cobs and they found that it has comparable attributes to Avicel® as a pharmaceutical excipient . Other work on MCC and cellulose derived from maize cobs have been reported [196,197].
|Dextran hydrogels have been shown to be the promising carrier for the delivery of drugs to colon [198-200].
|Cyclo dextrins (CyDs) are cyclic oligosaccharides consisting of six to eight glucose units joined through α-1, 4glucosidic bonds. CyDs remain intact during their passage through stomach and small intestine. However, in the colon, they undergo fermentation from the presence of vast colonic micro flora into small saccharides and thus absorbed from these regions [201,202]. CyDs form inclusion complexes with drug molecules because the interior of the molecule is relatively lipophilic while the exterior is hydrophilic . It has been investigated through a study in healthy human volunteers that β CyDs are degraded to a very small extent in the small intestine but are completely digested in large intestine. Most bacterial strains that are isolated from human beings are capable of degrading CyDs. This has been proved by their ability to grow on cyclo dextrins by utilizing them as the sole carbon source and by the stimulation of cyclo dextrinase activity as low as 2–4 hr of exposure to CyDs. This property of the drug may be exploited for the formation of colon targeted drug delivery systems. Several CyD conjugates have been prepared and the enantio selective hydrolysis has been described. Formulation of pro-drug of CyDs with drug molecules can provide a versatile means for construction of not only colon targeted delivery systems, but also delayed release systems. Biphenyl acetic acid (BPAA), an anti-inflammatory drug, was conjugated with α-, β- and γ -CyDs and in vivo release pattern was investigated in rat after oral administration. The CyD pro-drug maintained the physical integrity in stomach and small intestine which is reflected from the observations that the absorption of pro-drugs from upper GIT was negligible, and after 6 hr most of the pro-drug approached the caecum and colon. The α- and γ -CyD amide pro-drugs were hydrolyzed to the maltose conjugate in the colon while the α- and γ -CyD ester pro-drugs produced BPAA in the caecum and colon. The anti-inflammatory effect of the α- and γ -CyD ester pro-drugs was assessed and compared with those of BPAA alone and the drug CyD complex prepared by the kneading method in a molar ratio of 1:1. In the case of β-CyD complex, a rapid anti-inflammatory response was observed from the small intestine after a fast dissolution of the complex. In sharp contrast, the γ -CyD ester pro-drug required a fairly long lag time to exhibit the drug activity, because BPAA was produced after the pro-drug had reached the caecum and colon [203,204]. Some investigators  prepared two CyD conjugates: ester and amide conjugates. They showed that ester conjugate released the drug preferentially when incubated with the contents of caecum or colon, whereas no appreciable drug release was observed on incubation with the contents of either stomach or intestine in intestinal or liver homogenates or in rat blood. Systemic side effects of prednisolone were significantly reduced when conjugated with α-CyD . The lower side effect of the conjugate was attributed to passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specifically in the large intestine.
|Curdlan is a neutral, essentially linear (1”3)-β-glucan which may have a few intra- or inter-chain (1”6) linkages. Curdlan’s unusual rheological properties among natural and synthetic polymers underlie its use as a thickening and gelling agent in foods. Apart from being tasteless, colourless and odourless, the main advantages are that in contrast to cold-set gels and heat-set gels, the heating process alone produces different forms of curdlan gel with different textural qualities, physical stabilities and water-holding capacities . Gels of variable strength are formed depending on the heating temperature, time of heat-treatment and curdlan concentration. The safety of curdlan has been assessed in animal studies and in vitro tests and it is approved in food use in Korea, Taiwan and Japan as an inert dietary fibre. It is registered in the USA as a food additive (Figure 5).
|Among these macromolecules, scleroglucan (Sclg) also seems to be potentially useful for the formulation of modified release dosage forms and numerous studies have been devoted to this specific topic . Scleroglucan (Sclg) is a branched homo polysaccharide consisting of a main chain of (1-3)-linked b-D glucopyranosyl units bearing, every third unit, a single b-D-glucopyranosyl unit linked (1- 6). This polysaccharide is resistant to hydrolysis and its solutions show an interesting rheological behaviour: viscosity remains practically constant, even at high ionic strength, up to pH-12 and to 90oC.
|Interest in this polysaccharide was first aroused in 1967 . Sclg is a general term used to designate a class of glucans of similar structure produced by fungi, especially those of the genus Sclerotium. The commercial product is termed Scleroglucan, but it is also known with other names according to the company that produces the polysaccharide (e.g., Actigum, Clearogel, Polytetran, Polytran FS, Sclerogum). Because of its peculiar rheological properties and its resistance to hydrolysis, temperature and electrolytes, Sclg has various industrial applications, especially in the oil industry for thickening, drilling muds and for enhanced oil recovery and in food industry [209, 210]. In pharmaceutical products, Sclg may be used as a laxative in tablet coatings and in general to stabilize suspensions. Recently carboxymethyl derivative of scleroglucan (Scl-CM) with a 65±5% carboxylic group degree of derivatization (DD) was synthesized and characterized. Aqueous solutions of the polymer underwent to a sharp transition toward a gel like behavior in the presence of divalent ions such as Ca+2. Physical hydrogels with different Scl-CM/Ca+2 ratios were prepared and characterized for their rheological behavior. Their potential as drug delivery systems were also evaluated. To this end three non-steroidal anti-inflammatory drugs (NSAIDs) were loaded into the hydrogels obtained with 2% w/v solution of Scl-CM and 0.05 and 0.1 M CaCl2. The release rate of the drugs was critically related to the salt concentration. By an appropriate combination of the hydrogels prepared using different amounts of salt, it was possible to obtain a system able to release diclofenac with zero-order kinetics. Primary skin irritation tests showed a good biocompatibility of the new polymer, as well as of its hydrogels. These results suggested a potential of the new hydrogels for the development of modified delivery systems in oral and topical formulations [211,212].
|Rosin is a low molecular weight (400 Da) natural polymer obtained from the oleoresin of Pinussoxburghui, Pinuslongifolium and Pinustoeda. It has as components abietic and pimaric acids. Rosin and its derivatives have enjoyed growing roles in Pharmacy. They have been investigated for microencapsulation, film-forming and coating properties, and as matrix materials in tablets for sustained and controlled release [213,214].
|Studies on the film forming and coating properties of rosin and the glycerol ester of maleic rosin showed that rosin has excellent film forming properties with good to be used as coating materials for pharmaceutical products as well as in sustained-release drug delivery systems. The rosin films were biodegradable and biocompatible . Derivatives of rosin have been synthesized by reaction with polyethylene glycol 200 and maleic anhydride. The derivative proofed suitable for sustaining drug release from matrix tablets and pellets . Rosin nanoparticles loaded with hydrocortisone retarded the release of the active and demonstrated the potential of rosin production of effective nanoparticulate drug delivery systems .
|The research into and use of excipients from natural sources was reviewed and were discussed according to their classes. Natural polymeric excipients and their modifications have continued to dominate the research efforts of scientists in finding cheap, less expensive, biodegradable, ecofriendly excipients. Some of these excipients have obvious advantages over their synthetic counterparts in some specific delivery systems due to their inherent characteristics. If the current vigorous investigations on the use of natural polymeric materials are sustained and maintained, it is probable that there would be a breakthrough that will overcome some of the disadvantages of this class of potential pharmaceutical excipients that would change the landscape of the preferred pharmaceutical excipients for drug delivery in the future.
- Parrott EL (1971) Pharmaceutical Technology: Fundamental Pharmaceutics. Burgess Publishing Company, Minneapolis.
- IPECFED (2011) The world unites for safer medicines.
- Russell R (2004) Synthetic excipient challenge all-natural organics offer advantages/challenges to developer and formulators. Pharmaceutical Technology 38-50.
- Guo J, Skinner GW, Harcum WW, Barnum PE (1998) Pharmaceutical applications of naturally occurring water-soluble polymers. PSTT 1: 254-261.
- Beneke CE, Viljoen AM, Hamman JH (2009) Polymeric Plant-derived Excipients in Drug Delivery. Molecules 14: 2602-2620.
- Pandey R, Khuller GK (2004) Polymer based drug delivery systems for mycobacterial infections. Current Drug Delivery 1: 195-201.
- Chamarthy SP, Pinal R (2008) Plasticizer concentration and the performance of a diffusion-controlled polymeric drug delivery system. Colloids Surf A Physiochem Eng Asp 331: 25-30.
- Malafaya PB, Silva GA, Reis RL (2007) Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev 59: 207-233.
- Malviya R, Srivastava P, Kulkarni GT (2011) Applications of Mucilages in Drug Delivery - A Review. Advances in Biological Research 5: 1-7.
- Perepelkin KE (2005) Polymeric materials of the future based on renewable plant resources and biotechnologies. Fibre Chemistry 37: 417-430.
- Raizada A, Bandari A, Kumar B (2010) Polymers in Drug Delivery: A Review. International Journal of Pharmaceutical Research and Development 2: 9-20.
- Verbeken D, Dierckx S, Dewettinck K (2003) Exudate gums: occurrence, production and applications. Appl Microbiol and Biotechnol 63: 10-21.
- Maneesh K, Gaurav S, Ravinder K, Kapil K, Paramjot k, et al. (2010) Applications of novel excipients in the allopathic and herbal formulations. J Chem Pharm Res 2: 851-860.
- Cosgrove DJ (2005) Growth of the plant cell wall. Nat Rev Mol Cell Biol 6: 850-861.
- Kibbe AH (2000) Handbook of pharmaceutical excipients. The Pharmaceutical Press, Washington DC.
- Hon DNS (1996) Cellulose and its derivatives: Structures, Reactions and Medical Uses. Marcel Dekker, New York, USA.
- Andreopoulos AG, Trantali PA (2002) Study of biopolymers as carriers for controlled release. J Macromolecular science 41: 559-578.
- Conti S, Maggi L, Segale L, Machiste EO, Conte U, et al. (2007) Matrices containing NaCMC and HPMC 1. Dissolution performance characterization. International Journal of Pharmaceutics 333: 136-142.
- Scheller HV, Ulvskov P (2010) Hemicelluloses. Annu Rev Plant Biol 61: 263-289.
- Lerouxel O, Cavalier DM, Liepman AH, Keegstra K (2006) Biosynthesis of plant cell wall polysaccharides - a complex process. Curr Opin Plant Biol 9: 621-630.
- Katsuraya K, Okuyamab K, Hatanakab K, Oshimab R, Satoc T, et al. (2003) Constitution of konjac glucomannan: chemical analysis and 13C NMR spectroscopy. Carbohydrate Polymers 52: 183-189.
- Fan J, Wang K, Liu M, He Z (2008) In vitro evaluations of konjac glucomannan and xanthan gum mixture as the sustained release material of matrix tablet. Carbohydrate Polymer 73: 241-247.
- Sinha VR, Kumria R (2001) Polysaccharides in colon-specific drug delivery. International Journal of Pharmaceutics 224: 19-38.
- Sungthongjeen S, Pitaksuteepong T, Somsiri A, Sriamornsak P (1999) Studies on pectins as potential hydrogel matrices for controlled release drug delivery. Drug Development and Industrial Pharmacy 25: 1271-1276.
- Tho I, Sande SA, Kleinebudde P (2002) Pectinic acid: A novel excipient for production of pellets by extrusion/spheronisation: Preliminary studies. Eur J Pharm Biopharm 54: 95-99.
- Giunchedi P, Conte n U, Chetoni P, Saettone MF (1999) Pectin microspheres as ophthalmic carriers for piroxicam: Evaluation in vitro and in vivo in albino rabbits. Eur J Pharma Sci 9: 1-7.
- Musabayane CT, Munjeri O, Matavire TP (2003) Transdermal delivery of chloroquine by amidated pectin hydrogel matrix patch in the rat. Renal Fail 25: 525-534.
- Cheng K, Lim LY (2004) Insulin-loaded calcium pectinate nanoparticles: Effects of pectin molecular weight and formulation pH. Drug Deve Ind Pharm 30: 359-367.
- Liu L, Chen G, Fishman ML, Hicks KB (2005) Pectin gel vehicles for controlled fragrance delivery. Drug Deliv 12: 149-157.
- Sene C, Dupont A, Coring D (2004) Characterising polymeric excipients. Innovations in Pharmaceutical Technology 87-91.
- Sinha VR, Kumria R (2001) Polysaccharides in colon-specific drug delivery. International Journal of Pharmaceutics 224: 19-38.
- Friend DR (2005) New oral delivery systems for treatment of inflammatory bowel disease. Adv Drug Deliv Rev 57: 247-265.
- Rubinstein A, Radai R, Ezra M, Pathak S, Rokem JM (1993) In vitro evaluation of calcium pectinate: a potential colon-specific drug delivery carrier. Pharmaceutical Research 10: 258-263.
- Odeku OA, Fell JT (2005) In-vitro evaluation of khaya and albizia gums as compression coatings for drug targeting to the colon. J Pharm Pharmacol 57: 163-168.
- Semde R, Amighi K, Devleeschouwer MJ, Moes AJ (2000) Studies of pectin HM/Eudragit RL/Eudragit NE film-coating formulations intended for colonic drug delivery. Int J Pharm 197: 181-192.
- Claus EP, Tyler VE (1965) Pharmacognosy. Lea & Febiger, New York.
- Rana V, Rai P, Tiwary AK, Singh RS, Kennedy JF, et al. (2011) Modified gums: Approaches and applications in drug delivery. Carbohydrate Polymers 83: 1031-1047.
- Shah SN, Asghar S, Choudhry MA, Akash MS, ur Rehman N, et al. (2009) Formulation and evaluation of natural gum-based sustained release matrix tablets of flurbiprofen using response surface methodology. Drug Dev Ind Pharm 35: 1470-1478.
- Adetogun GE, Alebiowu G (2009) Properties of Delonix regia seed gum as a novel tablet binder. Acta Pol Pharm 66: 433-438.
- Morkhade DM, Joshi SB (2007) Evaluation of gum damar as a novel microencapsulating material for ibuprofen and diltiazem hydrochloride. Indian Journal of Pharmaceutical Sciences 69: 263-269.
- Tonnesen HH, Karlssen J (2002) Alginate in drug delivery systems. Drug Dev Ind Pharm 28: 621-630.
- Rajinikanth PS, Sankar C, Mishra B (2003) Sodium alginate microspheres of metoprolol tartrate for intranasal systemic delivery: Development and evaluation. Drug Deliv10: 21-28.
- Fuchs-Koelwel B, Koelwel C, Gopferich A, Gabler B, Wiegrebe E, et al. (2004) Tolerance of a new calcium-alginate-insert for controlled medication therapy of the eye. Ophthalmologe101: 496-499.
- Zeng WM (2004) Oral controlled release formulation for highly water-soluble drugs: Drug--sodium alginate--xanthan gum-zinc acetate matrix. Drug Development and Industrial Pharmacy 30: 491-495.
- Nerurkar J, Jun HW, Price JC, Park MO (2005) Controlled-release matrix tablets of ibuprofen using cellulose ethers and carrageenans: effect of formulation factors on dissolution rates. Eur J Pharm Biopharm 61: 56-68.
- Izydorczyk M (2006) Understanding the chemistry of food carbohydrates. Taylor and Francis, Boca Raton, FL, USA.
- Coviello T, Alhaique F, Dorigo A, Matricardi P, Grassi M (2007) Two galactomannans and scleroglucan as matrices for drug delivery: Preparation and release studies. European Journal of Pharmacy and Biopharmaceutics 66: 200-209.
- Sudhakar Y, Kuotsu K, Bandyopadhyay AK (2006) Buccal bioadhesive drug delivery - A promising option for orally less efficient drugs. Journal of Control Release 114: 15-40.
- Picker KM (1999) Matrix tablets of carrageenans. I. A compaction study. Drug Dev Ind Pharm 25: 329-337.
- Gupta VK, Hariharan M, Wheatley TA, Price JC (2001) Controlled-release tablets from carrageenans: effect of formulation, storage and dissolution factors. Eur J Pharm Biopharm 51: 241-248.
- Mohamadnia Z, Zohuriaan-Mehr MJ, Kabiri K, Jamshidi A, Mobedi H (2008) Ionically crosslinked carrageenan-alginate hydrogel beads. J Biomater Sci Polym Ed 19: 47-59.
- Bhardwaj TR, Kanwar M, Lal R, Gupta A (2000) Natural gums and modified natural gums as sustained-release carriers. Drug Dev Ind Pharm 26: 1025-1038.
- Parija S, Misra M, Mohanty AK (2001) Studies of natural gum adhesive extracts - An overview. Polymer Reviews 4: 175-197.
- Whistler RL, Smart CL (1953) Polysaccharide Chemistry. Academic Press, New York, USA.
- Becker A, Katzen F, Pühler A, Ielpi L (1998) Xanthan gum biosynthesis and application: a biochemical/genetic perspective. Appl microbiol Biotechnol 50: 145-152.
- Rosalam S, England R (2006) Review of xanthan gum production from unmodified starches by Xanthomonas comprestris sp. Enzyme and Microbial Technology 39: 197-207.
- Garcia-Ochoa F, Santos VE, Casas JA, Gomez E (2000) Xanthan gum: production, recovery, and properties. Biotechnology Advances 18: 549-579.
- Yoshida T (1993) Bioproducts and bioprocess. Springer-Verlag, Berlin, Heidelberg, Germany.
- Mundargi RC, Patil SA, Aminabhavi TM (2007) Evaluation of acrylamide-grafted-xanthan gum copolymer matrix tablets for oral controlled delivery of antihypertensive drugs. Carbohydrate Polymers 69: 130-141.
- Talukdar MM, Kinget R (1995) Swelling and drug release behaviour of xanthan gum matrix tablets. Int J Pharm120: 63.
- Vendruscolo CW, Andreazza IF, Ganter JL, Ferrero C, Bresolin TM (2005) Xanthan and galactomannan (from M. scabrella) matrix tablets for oral controlled delivery of theophylline. Int J Pharm 296: 1-11.
- Vandamme EJ, Baets S, Steinbüchel A (2002) Biopolymers - Polysaccharides I, Wiley-VCH Verlag GmbH. Weinheim, Germany.
- Miyoshi E, Takaya T, Nishinari K (1996) Rheological and thermal studies of gel-sol transition in Gellan gum aqueous solutions. Carbohydrate Polymer 30: 109-119.
- Grasdalen H, Smidsroed O (1987) Gelation of Gellan gum. Carbohydrate Polymer 7: 371-393.
- Crescenzi V, Dentini M, Coviello T, Rizzo R (1986) Comparative analysis of the behavior of Gellan gum (S-60) and welan gum (S-130) in dilute aqueous solution. Carbohydrate Research 149: 425-432.
- Horinaka J, Kani K, Hori Y, Maeda S (2004) Effect of pH on the conformation of Gellan chains in aqueous systems. Biophysical Chemistry 111: 223-227.
- Miyazaki S, Aoyama H, Kawasaki N, Kubo W, Attwood D (1999) In situ gelling Gellan formulations as vehicles for oral drug delivery. J control release 55: 287-295.
- Agnihotri SA, Jawalkar SS, Aminabhavi TM (2006) Controlled release of cephalexin through Gellan gum beads: Effect of formulation parameters on entrapment efficiency, size, and drug release. Eur J Pharm Biopharm 63: 249-261.
- Agnihotri SA, Aminabhavi TM (2005) Development of novel interpenetrating network Gellan gumpoly (vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol. Drug Dev Ind Pharm 31: 491-503.
- Coviello T, Dentini M, Rambone G, Desideri P, Carafa M, et al. (1998) A novel co-cross linked polysaccharide: studies for a controlled delivery matrix. J Control Release 60: 287-295.
- Matricardi P, Cencetti C, Ria R, Alhaique F, Coviello T (2009) Preparation and Characterization of Novel Gellan Gum Hydrogels Suitable for Modified Drug Release. Molecules 14: 3376-3391.
- Popa M, Åzunel V, Rusu L (2003) Immobilization of 1-[N-(M-Nitrobenzoyl)-Î±-D,L-Asparagyl]-2-Benzylbenzimidazole on Gellan. Molecules 8:297-309.
- Akiyoshi K, Kobayashi S, Shichibe S, Mix D, Baudys M, et al. (1998) Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. J control release 54: 313-320.
- Ramakrishnan A, Pandit N, Badgujar M, Bhaskar C, Rao M (2007) Encapsulation of endoglucanase using a biopolymer gum arabic for its controlle lease. Bioresour Technol 98: 368-372.
- Nishi KK, Antony M, Mohanan PV, Anilkumar TV, Loiseau PM, et al. (2007) Amphotericin B-Gum arabic conjugates: synthesis, toxicity, bioavailability, and activities against Leishmania and fungi. Pharm Res 24: 971-980.
- Lu EX, Jiang ZQ, Zhang QZ, Jiang XG (2003) A water-insoluble drug monolithic osmotic tablet system utilizing gum arabic as an osmotic, suspending and expanding agent. J Control Release 92: 375-382.
- Anderson DMW, Stoddart JF (1966) Studies on uronic acid materials: Part XV. The use of molecular-sieve chromatography in studies on acacia senegal gum (gum arabic). Carbohydrate Research 2: 104-114.
- Aspinall GO, Baillie J (1963) Gum tragacanth. Part I Fractionation of the gum and the structure of tragacanthic acid. Journal of the Chemical Society (Resumed) 1963: 1702-1714.
- Anderson DMW, Bridgeman MME (1985) The composition of the proteinaceous polysaccharides exuded by astragalus microcephalus, A. Gummifer and A. Kurdicusâ-The sources of turkish gum tragacanth. Phyto chemistry 24: 2301-2304.
- Anderson DMW, Grant DAD (1988) The chemical characterization of some Astragalus gum exudates. Food Hydrocolloids 2: 417-423.
- Philips GO, Williams PA (2000) Handbook of Hydrocolloids. CRC press, New York, USA.
- Sima B, Mohammad AM, Azizollaah Z (2010) Physicochemical and Rheological Characterization of Gum Tragacanth Exudates from Six Species of Iranian Astragalus. Food Biophysic 5: 57-71.
- Prabaharan M (2011) Prospective of guar gum and its derivatives as controlled drug delivery systems. Int J Biol Macromol 49: 117-124.
- Krishnaiah YS, Karthikeyan RS, Satyanarayana V (2002) A three-layer guar gum matrix tablet for oral controlled delivery of highly soluble metoprolol tartrate. Int J Pharm 241: 353-366.
- Krishnaiah YS, Karthikeyan RS, Gouri Sankar V, Satyanarayana V (2002) Three-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride. Journal of controlled release 81: 45-56.
- Prasad YV, Krishnaiah YSR, Satyanarayana S (1998) In vitro evaluation of guar gum as a carrier for colon-specific drug delivery. J control release 51: 281-287.
- Toti US, Aminabhavi TM (2004) Modified guar gum matrix tablet for controlled release of diltiazem hydrochloride. J control release 95: 567-577.
- Heywood VH, Brummitt RK, Culham A, Seberg O (2007) Flowering Plant Families of the World. Firefly Books, Richmond Hill, Ontario, Canada.
- Wikipedia (2010) Grewia, wikipedia encyclopedia.
- Wikipedia (2010) Carl Linnaeus, wikipedia encycopedia.
- Sprague TA (1909) The Section Microcos of Grewia in Africa. Bulletin of Miscellaneous Information, Royal Botanic Gardens. Kew 66-68.
- Onwuliri FC, Mawak JD, Wonang DL, Onwuliri EA (2006) Phytochemical toxicological and histo-pathological studies of some medicinal plants in Nigeria. International Journal of Natural and Applied Sciences 2: 225-229.
- Okafor IS (2001) Characterization and application of grewia gum in tabletting. In Pharmaceutics, University of Nigeria, Nsukka.
- Okafor IS (2001) The rheological properties of grewia gum. Nigeria Journal of Polymer Science and Technology 2: 169-175.
- Okafor IS, Chukwu A (2003) Water vapor permeability of aqueous-based grewia gum film. Nigeria Journal of Polymer Science and Technology.
- Okafor IS, Chukwu A (2003) The binding property of grewia gum in sodium salicylate tablets. West African Journal of Biological Sciences14: 9-21.
- Okafor IS, Chukwu A, Udeala OK (2001) Some physicochemical properties of grewia gum. Nigeria Journal of Polymers Science and Technology 2: 161-168.
- Okafor IS, Danat IM (2004) The influence of granulating solvents on drug release from tablets containing grewia gum. Journal of Pharmacy and Bioresources 1: 76-83.
- Audu-Peter JD, Gokum BG (2005) Effect of methods of incorporating grewia gum as binder on tablet properties. Nigerian Journal of Pharmaceutical Research 4: 68-73.
- Audu-Peter JD, Isah S (2007) Evaluation of grewia gum as binder in paracetamol tablet. Journal of Pharmacy and Bioresources 4:68-73.
- Emeje M, Isimi C, Kunle O (2008) Effect of Grewia gum on the mechanical properties of Paracetamol tablet formulations. African Journal of Pharmacy and Pharmacology 2:1-6.
- Muazu J, Musa H, Musa KY (2009) Compression, mechanical and release properties of paracetamol tablets containing acid treated Grewia gum. Journal of Pharmaceutical Science and Technology1: 74.
- Nep EI, Conway BR (2010) Characterization of Grewia Gum, a Potential Pharmaceutical Excipient. Journal of Excipients and Food Chemistry 1: 30-40.
- Ogaji I (2011) Characterization and application of grewia gum as a film coating agent in theophylline hydrochloride tablets. In Pharmacetics and Pharmaceutical Technology 308.
- Ndjouenkeu R, Akingbala J, Oguntimein G (1997) Emulsifying properties of three African food hydrocolloids: okra (Hibiscus esculentus), dika nut (Irvingia gabonensis) and khan (Belschmiedia sp.). Plant Foods for Human Nutrition (Formerly Qualitas Plantarum) 51: 245-255.
- Udayasekhara Rao P (1985) Chemical composition and biological evaluation of Okra (Hibiscus esculentus) seeds and their kernels. Plant Foods for Human Nutrition (Formerly Qualitas Plantarum) 35: 389-396.
- Acquistucci R, Francisci R (2002) Effect of okra (Hibiscus esculentus L) addition on the technological properties of wheat flour. Int J Food Sci Nutr 53: 375-379.
- Al-Wandawi H (1983) Chemical composition of seeds of two okra cultivm. J Agric Food Chem 31: 1355-1358
- Falade KO, Omojola BS (2010) Effect of processing methods on physical, chemical, rheological, and sensory properties of okra (Abelmoschus esculentus). Food and Bioprocess Technology 3: 387-394.
- Inyang UE, Ike CI (1998) Effect of blanching, dehydration method and temperature on the ascorbic acid, colour, sliminess and other constituents of okra fruit. Int J Food Sci Nutr 49:125-130.
- Kalra CL, Raina BL, Testia MS, Pruthi JS, Sharma BR et al. (1983) The influence of varieties on the quality of dehydrated okra. Ind Food Packer 37: 47.
- Ndjouenkeu R, Goycoolea FM, Morris ER, Akingbala JO (1996) Rheology of okra (Hibiscus esculentus L) and dikanut (Irvingia gabonensis) polysaccharides. Carbohydrate Polymer 29: 263-269.
- Olorunda AO, Tung MA (1977) Rheology of fresh and frozen okra dispersions. International Journal of Food Science & Technology 12: 593-598.
- Romanchik-Cerpovicz JE, Costantino AC, Gunn LH (2006) Sensory Evaluation Ratings and Melting Characteristics Show that Okra Gum Is an Acceptable Milk-Fat Ingredient Substitute in Chocolate Frozen Dairy Dessert. J Am Diet Assoc 106: 594-597.
- Romanchik-Cerpovicz JE, Tilmon RW, Baldree KA (2002) Moisture Retention and Consumer Acceptability of Chocolate Bar Cookies Prepared With Okra Gum as a Fat Ingredient Substitute. Journal of the American Dietetic Association 102: 1301-1303.
- Savello PA, Marin FW, Hill JM (1980) Nutritional composition of okra seed meal. J Agric Food Chem 28: 1163-1166.
- Sengkhamparn N, Sagis L, De Vries R, Schols HA, Sajjaanantakul T, et al. (2010) Physicochemical properties of pectins from okra (Abelmoschus esculentus (L.) Moench). Food Hydrocolloids 24: 35-41.
- Stone MB, Toure D, Greig JK, Naewbaniji JO (1986) Effect of pretreatment and dehydration temperature on colour, nutrient retention and sensory characteristics of okra. Journal of Food Science 51: 1201-1203.
- Uzo JO, Ojiako GU (1980) A physical method for measuring okra fruit quality. Journal of Food Science 45: 390-391.
- Nasipuri RN, Igwilo CI, Brown AS, Kunle OO (1996) Mucilage from Abelmoschus esculentus (okra) fruits: a potential pharmaceutical raw material; part I; physicochemical properties. Journal of Pharmaceutical Research and Development 1: 22-28.
- Tavakoli N, Ghasemi N, Taimouri R, Hamishehkar H (2004) Evaluation of okra gum as a binder in tablet dosage forms. Iranian Journal of Pharmaceutical Research Res 2: 47.
- Momoh MA, Akikwu MU, Ogbona JI, Nwachi UE (2009) In Vitro Study of Release of Metronidazole Tablets Prepared from Okra Gum, Gelatin Gum and their Admixture. Bio-Research 6: 339-342.
- Kalu VD, Odeniyi MA, Jaiyeoba KT (2007) Matrix properties of a new plant gum in controlled drug delivery. Arch pharm res 30: 884-889.
- Ogaji I, Nnoli O (2010) Film coating potential of okra gum using paracetamol tablets as a model drug. Asian Journal of Pharmaceutics 4: 130-134.
- Attama AA, Adikwu MU, Amorha CJ (2003) Release of indomethacin from bioadhesive tablets containing Carbopol 941 modified with Abelmuschus esculentus (Okra) gum. Boll Chim Farm 142: 298-302.
- Ogaji I (2011) Some physicochemical properties of acetaminophen pediatric suspensions formulated with okra gums obtained from different extraction processes as suspending agent. Asian Journal of Pharmaceutics 5: 15-20.
- Nasipuri RN, Igwilo CI, Brown SA, Kunle OO (1996) Mucilage from Abelmuschus esculentus (okra) fruits- a potential pharmaceutical raw material; part1; physicochemical properties. Journal of Pharmaceutical Research and Development 1: 22-28.
- Femi-Oyewo MN, Adedokun MO, Olusoga TO (2004) Evaluation of the suspending proerties of Albizia zygia gum on sulphadimidine suspension. Tropical Journal of Pharmaceutical Research 3: 279-284.
- Kalu VD, Odeniyi MA, Jaiyeoba KT (2007) Matrix Properties of a New Plant Gum in Controlled Drug Delivery. Archives of Pharmaceutical Research 30: 884-889.
- Adenuga YA, Odeku OA, Adegboye TA, Itiola OA (2008) Comparative evaluation of the binding properties of two species of Khaya gum polymer in a paracetamol tablet formulation. Pharm Dev Technol 13: 473-480.
- Anoop Kumar Singh, Panner Selvam R, Sivakumar T (2010) Isolation, characterisation and formulation properties of a new plant gum obtained from mangifera indica. Int J Pharma Biomedical Res 1: 35-41.
- Joseph JK (1995) Physico-chemical attributes of wild mango (Irvingia gabonensis) seeds. Bioresource Technology 53: 179-181.
- Joseph K, Aworh OC (1991) Composition, sensory quality and respiration during ripening and storage of edible wild mango (Irvingia gabonensis). International Journal of Food Science & Technology 26: 337-342.
- Joseph K, Aworh OC (1992) Post-harvest treatment of wild mango (Irvingia gabonensis) for improved shelf life. Food Chemistry 44: 45-48.
- Kuete V, Wabo GF, Mbaveng AT, Metuno R, Etoa FX, et al. (2007) Antimicrobial activity of the methanolic extract, fractions and compounds from the stem bark of Irvingia gabonensis(ixonanthaceae). J Ethnopharmacology 114: 54-60.
- Aina JO (1990) Physico-chemical changes in African mango (Irvingia gabonensis) during normal storage ripening. Food Chemistry 36: 205-212.
- Eka O (1980) Proximate composition of bush mango tree and some properties of dika fat. Nigerian Journal of Nutrition Science1: 33-36.
- Abbiw D (1990) Useful plants of Ghana, Intermediate Technology Publications and the Royal Botanical Garden. Kew, London.
- Atangana AR, Ukafor V, Anegbeh P, Asaah E, Tchoundjeu Z, et al. (2002) Domestication of Irvingia gabonensis: 2. The selection of multiple traits for potential cultivars from Cameroon and Nigeria. Agro forestry Systems 55: 221-229.
- Ayuk ET, Duguma B, Franzel S, Kengue J, Mollet M, et al. (1999) Uses, management and economic potential of Irvingia gabonensis in the humid lowlands of Cameroon. Forest ecology and management 113: 1-9.
- Adeyeye EI, Arogundade LA, Akintayo ET, Aisida OA, Alao PA (2000) Calcium, zinc and phytate interrelationships in some foods of major consumption in Nigeria. Food Chemistry 71: 435-441.
- Onyeike EN, Olungwe T, Uwakwe AA (1995) Effect of heat-treatment and defatting on the proximate composition of some Nigerian local soup thickeners. Food Chemistry 53:173-175.
- Uzoma A, Ahiligwo RN (1999) Studies on the rheological properties and functional potentials of achi (Brachystega eurycoma) and ogbono (Irvingia gabonesis) seed gums. Food Chemistry 67: 217-222.
- Akubor PI (1996) The suitability of African bush mango juice for wine production. Plant Foods for Human Nutrition (Formerly Qualitas Plantarum) 49: 213-219.
- Fajimi O, Sarumi MB, Olayode MN, Gamra EO, Sanusi SI (2010) Sanusi SI In vitro propagation of Irvingia gabonensis. African Journal of Biotechnology 6.
- Giami SY, Okonkwo VI, Akusu MO (1994) Chemical composition and functional properties of raw, heat-treated and partially proteolysed wild mango (Irvingia gabonensis) seed flour. Food Chemistry 49: 237-243.
- Raji Y, Ogunwande IA, Adesola JM, Bolarinwa AF (2001) Anti-Diarrhegenic and Anti-Ulcer Properties of Irvingia gabonensis in Rats. Pharmaceutical Biology 39: 340-345.
- Njoku OU, Ugwuanyi JO (1997) Nutritional and toxicological properties of dika fat (Irvingia gabonensis). Journal of Herbs Spices & Medicinal Plants 4: 53-58.
- Ngondi JL, Oben JE, Minka SR (2005) The effect of Irvingia gabonensis seeds on body weight and blood lipids of obese subjects in Cameroon. Lipid Health Dis 4: 12.
- Nguyen-Pouplin J, Tran H, Tran H, Phan TA, Dolecek C, et al. (2007) Antimalarial and cytotoxic activities of ethnopharmacologically selected medicinal plants from South Vietnam. J Ethnopharmacol 109: 417-427.
- Ozolua RI, Eriyamremu GE, Okene EO, Ochei U (2006) Hypoglycemic effects of viscous preparations of Irvingia gabonensis (dikanut) seeds in streptozotocin-induced diabetic wistar rats. Journal of Herbs Spices & Medicinal Plants 12: 1-9.
- Wolfe OA, Ijeoma UF (2010) Effects of aqueous extracts of Irvingia gabonensis seeds on the hormonal parameters of male guinea pigs. Asian Pacific Journal of Tropical Medicine 3: 200-204.
- Odeku OA, Patani B (2005) Evaluation of dika nut mucilage (Irvingia gabonensis) as a binding agent in metronidazole tablet formulation. Pharm Dev Technol 10: 439-446.
- Ofoefule SI, Chukwu A (2001) Effects of polyethyleneglycol 4000 and sodium lauryl sulphate on the release of hydrochlorothiazide embedded in the dika fat matrix. Acta pharmaceutica 51: 233-239.
- Ofoefule SI, Chukwu A, Okore VC, Ugwah MO (1997) Use of dika fat in the formulation of sustained release frusemide encapsulated granules. Boll chim Farm 136: 646-650.
- Okafor JC (1975) Varietal delimitation in Irvingia gabonensis (Irvingiaceae). Bull Jard bot nat Belg/Bull Nat Plantentuin Belg 45: 211-221.
- Okolo CO, Johnson PB, Abdulraham EM, Abdu-Aguye I, Hussaini IM (1995) Analgesic effects of Irvingia gabonensis stem bark extract. Journal of Ethnopharmacology 45: 125-129.
- Okore VC (1998) Evaluation of dika fat as a suppository base: Factors which affect the drug release from dika fat-based suppositories. Acta Pharm 48: 39-46.
- Okore VC (1994) Evaluation of Dika Fat as a Suppository Base II: Thermal and Release Characteristics of Blended Dika Fat Suppositories. Drug Development & Industrial Pharmacy 20: 93-100.
- Okore VC, Udeala OK (2004) GC-MS Analysis of fatty acids of irvingia gabonensis seed fat. Nig J Nat Prod &Med 1: 43-44.
- Onyechi JO (2009) Preformulation compatibility screening of dika fat-drug mixtures using differential scanning calorimetry. Bio-Research 7: 465-469.
- Onyechi JO, Udeala OK (1990) The Tabletting Properties of Dika Fat Lubricant. Drug Development and Industrial Pharmacy 16: 1203-1216.
- Tairu AO, Hofmann T, Schieberle P (2000) Studies on the key odorants formed by roasting of wild mango seeds (Irvingia gabonensis). J Agric Food Chem 48: 2391-2394.
- Abdurahman EM, Rau PP, Shok M, Olurinola PF, Laakso I (1996) Analysis of the fatty acid composition of the seed fat of two varieties of Irvingia gabonensis by high resolution gas chromatography. J Pharm Res Develop 1: 48-49.
- Amubode FO, Fetuga BL (1984) Amino acid composition of seeds of some lesser known tree crops. Food Chemistry 13: 299-307.
- Lewkowitsch J (1905) Dika fat. The Analyst 30: 394-395.
- Meara ML, Patel CB (1950) The component acids and glycerides of dika fat. Journal of the Science of Food & Agriculture1: 48-51.
- Isimi CY, Kunle OO, Bangudu AB (2000) Some emulsifying and suspending properties of the mucilage extracted from kernels of Irvingia gabonensis. Boll Chim Farm 139: 199-204.
- Udeala OK, Onyechi JO, Agu SI (1980) Preliminary evaluation of dika fat, a new tablet lubricant. J Pharma Pharmacol 32: 6-9.
- Umekoli GC, Onyechi JO, Udeala OK (2009) Use of dika fat in the formulation of sustained release theophylline tablets and capsules. Bio-Research 7: 456-460.
- Udeala OK, Aly SAS (1986) The effects of microencapsulation with dika wax on the degradation and dissolution of aspirin tablets. Drug Development and Industrial Pharmacy12: 397-421.
- Megwa SA (1987) Evaluation of dika fat as a suppository base. Drug Development and Industrial Pharmacy 13: 2731-1748.
- Womeni HM, Ndjouenkeu R, Kapseu C, Mbiapo FT, Parmentier M, et al. (2008) Aqueous enzymatic oil extraction from Irvingia gabonensis seed kernels. European Journal of Lipid Science and Technology 110: 232-238.
- Dudu PO, Okiwelu SN, Lale NES (1998) Attractancy of diethyl ether extracts of Arachis hypogaea (Linnaeus) (Papilionaceae), Citrullus lanatus (Thunberg) (Cucurbitaceae) and Irvingia gabonensis var. excelsa (Baillon) (Irvingiaceae) to Oryzaephilus mercator (Fauvel) (Coleoptera: Silvanidae). Journal of Stored Products Research 34: 237-241.
- Ogaji I, Anjan N, Hoag SW (1996) A Novel Extraction Method and Some Physico-chemical Properties of Extractives of Irvingia gabonensis seeds. Journal of Young Pharmacists 23: 45-49.
- Alur HH, Pather SI, Mitra AK, Johnston TP (1999) Evaluation of the Gum from Hakea gibbosa as a Sustained-Release and Mucoadhesive Component in Buccal Tablets. Pharm Deve Technol 4: 347-358.
- Tyler VE, Brady LR, Robers JE (1981) Plant Gums and Mucilage. 8thedn, Lea and Febiger, Philadelphia.
- Kulkarni GT, Gowthamrajan K, Rao BG, Suresh B (2002) Evaluation of binding properties of plantago ovate and Trigonella foenum graecum mucilages. Indian Drugs 38: 422-425.
- Singh B, Chauhan N (2009) Modification of psyllium polysaccharides for use in oral insulin delivery. Food Hydrocolloids 23: 928-935.
- Namdeo B, Vidya I, Sushilkumar P (2008) Swelling and erosion modulation of Sterculia foetida through real time texture probing. Dhaka University Journal of Pharmaceutical Sciences 7: 127-132.
- Chukwu KI, Udeala OK (2000) Binding effectiveness of Colocassia esculenta gum in poorly compressible drugs-paracetamol and metronidazole tablet formulations. Boll chim farm 139: 89-97.
- Baveja SK, Ranga Rao KV, Arora J (1988) Examination of natural gums and mucilages as sustaining materials in tablet dosage forms. Indian J Pharm Sci 50: 89-92.
- Somboonpanyakul P, Wang Q, Cui W, Barbut S, Jantawat P (2006) Malva nut gum. (Part I): Extraction and physicochemical characterization. Carbohydrate Polymers 64: 247-253.
- Vervoort L, Kinget R (1996) In vitro degradation by colonic bacteria of inulin HP incorporated in Eudragit films. International Journal of Pharmaceutics 129: 185-190.
- Vervoort L, Van den Mooter G, Augustijns P, Busson R, Toppet S, et al. (1997) Inulin hydrogels as carrier for colonic drug targeting .I. Synthesis and characterization of methacrylated inulin and hydrogel formation. Pharmaceutical Research 14: 1730-1736.
- Larionova NV, Ponchel G, Duchene D, Larionova NI (1999) Biodegradable cross-linked starch/protein microcapsules containing proteinase inhibitor for oral protein administration. International Journal of Pharmaceutics 189: 171-178.
- Tuovinen L, Peltonen S, Jarvinen K (2003) Drug release from starch-acetate films. Journal of Control Release 91: 345-354.
- Krogars K, Antikainen O, Heinamaki J, Laitinen N, Yliruusi J (2002) Tablet film coating with amylose-rich maize starch. European Journal of Pharmaceutical Sciences 17: 23-30.
- Milojevic S, Newton JM, Cummings JH, Gibson GR, Botham RL, et al. (1995) Amylose, the new perspective in oral drug delivery to the human large intestine. STP Pharma Sciences 5: 47-53.
- Milojevic S, Newton JM, Cummings JH, Gibson GR, Botham RL, et al. (1996) Amylose as a coating for drug delivery to the colon: preparation and an in vitro evaluation using 5-aminosalicylic acid pellets. Journal of Control Release 38: 75-84.
- Milojevic S, Newton JM, Cummings JH, Gibson GR, Botham RL, et al. (1996) Amylose as a coating for drug delivery to the colon: preparation and in vitro evaluation using glucose pellets. Journal of Control Release 38: 85-94.
- Palviainen P, Heinamaki J, Myllarinen P, Lahtinen R, Yliruusi J, et al. (2001) Corn starches as film formers in aqueous-based film coating. Pharmaceutical Development and Technology 6: 351-361.
- Siew LF, Basit AW, Newton JM (2000) The potential of organic based amylose-ethylcellulose film coatings as oral colon specific drug delivery systems. AAPS PharmSciTech 1: E22.
- Audu-Peter JD, Ojile JE, Bhatia PG, Bukar BB (2002) Evaluation of properties of direct compression paracetaoml tablet containing only microcrystalline cellulose derived from maize cobs. West African Journal of Biological Sciences 13: 43-50.
- Audu-Peter JD, Ojile JE, Bhatia PG (2004) Physicochemical and powder properties of alpha- and microcrystalline-cellulose derived from maize cobs. Journal of Pharmacy and Bioresources 1: 41-45.
- Audu-Peter JD, Adegboye SY (2007) Comparative properties of paracetamol tablets prepared by direct and multiple compressions using cellulose derived from maize cobs. Journal of Medical and Pharmaceutical Sciences 3: 35-39.
- Audu-Peter JD, Amedu O (2008) Properties of aspirin tablets prepared by direct and multiple compressions using cellulose derived from maize cobs. Journal of Advance Medical and Pharmaceutical Sciences 2: 25-29.
- Brondsted H, Hovgaard L, Simonsen J (1995) Dextran hydrogels for colon-specific drug delivery. IV. Comparative release mechanism of hydrocortisone and prednisolone phosphate. STP Pharmaceutical Sciences 5: 65-69.
- Simonsen L, Hovgaard L, Mortensen PB, Bronsted H (1996) Dextran hydrogels for colon-specific drug delivery.V.Degradation in human intestinal incubation models. European Journal of Pharmaceutical Sciences 3: 329-337.
- Hovgaard L, Brondsted H (1995) Dextran hydrogels for colon-specific drug delivery. Journal of Controlled Release 36: 159-166.
- Flourie B, Molis C, Achour L, Dupas H, Hatat C, et al. (1993) Fate of ß-cyclodextrin in the human intestine. J Nutr 123: 676-680.
- Stella VJ, Rajewski RA (1997) Cyclodextrins, their future in drug formulation and delivery. Pharm Res 14: 556-567.
- Minami K, Hiramaya F, Uekama K (1998) Colon-specific drug delivery based on a cyclodextrin prodrug, release behaviour of biphenyl acetic acid from its cyclodextrin conjugates in rat intestinal tracts after oral administration. J Pharm Sci 87: 715-720.
- Uekama K, Minami K, Hirayama F (1997) 6-A-O-[(4-biphenylyl)acetyl)]-alpha-, -beta- and -gamma-cyclodextrins and 6A-deoxy-6A-[[(4-biphenyl)-acetyl]amino]-alpha-, -beta-, and -gamma-cyclodextrins, potential prodrugs for colon-specific delivery. J Med Chem 40: 2775-2761.
- Hiramaya F, Minami K, Uekama K (1996) In vitro evaluation of biphenyl acetic acid-beta-cyclodextrin conjugates as colon-targeting prodrugs, Drug release behaviour in rat biological media. J Pharm Pharm 48: 27-31.
- Yano H, Hirayama F, Kamada M, Arima H, Uekama K (2002) Colon-specific delivery of prednisolone-appended a-cyclodextrin conjugate, alleviation of systemic side effect after oral administration. J control release 79: 103-112.
- Jezequel V (1998) Curdlan: A New Functional Beta-Glucan. Cereal Foods World 43: 361-364.
- De Baets S, Vandamme EJ, Steinbüchel A (2002) Biopolymers. Wiley-VCH, New York.
- Halleck FE (1967) Polysaccharides and methods for production thereof. In Chem Abstract, USA.
- Singh PP, Wisler RL, Tokuzen R, Nakahara W (1974) Scleroglucan, an antitumor polysaccharide from Sclerotium glucanicum. Carbohydr Res 37: 245-247.
- Corrente F, Matricardi P, Paolicelli P, Tita B, Vitali F, et al. (2009) PhysicalCarboxymethylscleroglucan/Calcium Ion Hydrogels as Modified Drug Delivery Systems in Topical Formulations. Molecules 14: 2684-2698.
- Coviello T, Palleschi A, Grassi M, Matricardi P, Bocchinfuso G, et al. (2005) Scleroglucan: A Versatile Polysaccharide for Modified Drug Delivery. Molecules 10: 6-33.
- Mandaogade PM, Satturwar PM, Fulzele SV, Gogte BB, Dorle AK (2002) Rosin derivatives: novel film forming materials for controlled drug delivery. Reactive Functional Polymer 50: 233-242.
- Fulzele SV, Satturwar PM, Dorle AK (2003) Study of the biodegradation and in vivo biocompatibility of novel biomaterials. Eur J Pharm Sci 20: 53-61.
- Nande VS, Barabde UV, Morkhade DM, Patil AT, Joshi SB (2006) Synthesis and characterization of PEGylated derivatives of rosin for sustained drug delivery. Reactive Functional Polymers 66: 1373-1383.
- Lee CM, Lim S, Kim GY, Kim DW, Joon HR, et al. (2005) Rosin nanoparticles as a drug delivery carrier for the controlled release of hydrocortisone. Biotechnol Lett 27: 1487-1490.