Tamarind Seed Polysaccharides : A Novel Carrier For Drug Delivery Systems
Tamarind products are highly developed and widely used in Asia and so far little used in Africa, although syrup and jam are made from fruits.
In India and Thailand especially, cultivars are grown and the food industry is active. Tamarind gum or Tamarind Seed Polysaccharides (TSP) (or hydrocolloid) is a polysaccharide polymer (D-galactose, D-xylose and D-glucose) obtained from endosperm of kernels of seeds. The polysaccharide constitutes about 65 percent of the seed components (Rao PS and Srivastav HC 1982; Meier H and Reid JSG 1999; Leakey 1973). It is extracted, purified and refined and used as a thickening, stabilizing and gelling agent in foods, especially in Japan where Dainippon Pharmaceutical Co conducted two years of feeding toxicity tests (Glicksman M 1986). In India it is the chief acidifying agent in curries, chutneys, and sauces. The gum can also be used as a binder in pharmaceutical tablets, as a humectant and emulsifier (Hulse J 1996). Proximate analysis of seed kernels shows that 65.1-72.2% is non-fiber carbohydrate, 15.4-22.7% is protein 3.9- 7.4% is oil and 0.7-8.2% is crude fiber.
Two main products are used by the food industry:
(i) Tamarind kernel powder (TKP), which contains about 50% gum and (ii) Tamarind gum polysaccharide (TGP), the purified product that is virtually 100% pure. These two products have different specifications (Glicksman M. 1986) and uses. TSP has the ability to form gels in the presence of sugar or alcohol and can be used to form pectin like gels in jams, jellies and other preserves (Glicksman M. 1986). The xyloglucan from tamarind seeds offer no chemical advantage over guar gum as a viscosifier, but tamarind flour is cheaper indicating that a bioprocess to upgrade the tamarind polysaccharide might be commercially viable (Reid JSG & Edwards ME 1995).
2. Isolation Of TSP
TSP was prepared following methods by Rao PS et al. 1946; Rao PS and Srivastava HC 1975; Nandi RC et al. 1973) on a laboratory scale.
3. Chemical Structure
TSP is a polymer with an average molecular weight of 52,350 and a monomer of mainly three sugars—glucose, galactose, and xylose—in a molar ratio of 3:1:2 (Khanna M 1987)
There have been numerous publications in the past 30 years concerning the primary structure of TSP. There is general agreement about the nature of the backbone and the side chains. The polymer consists of a cellulose-type spine, which carries xylose and galactoxylose substituents. About 80% of the glucose residues are substituted by a 1+6 linked xylose units, which themselves are partially substituted by p 1-2 galactose residues. These structural units are displayed in Figure 1 (Lang P 1993)
Figure 1 Average primary structure of tamarind seed polysaccharide. The cellulose type backbone is substituted by xylose(a 1-6) and galacto(8 l-c2)xylose(cu 1-6) residues.
It is the branched polysaccharides with main chain of β-D-(14) linked glucopyranosyl units and that a side chain consisting of single D-xylopyranosyl unit attached to every second, third and fourth D-glucopyranosyl unit through a a-D-(16) linkage. One D-galactopyranosyl unit is attached to one of the xylopyranosyl unit through a ί-D-(12) linkage. (Gerard T 1980 and Gidley M et al. 1991)
Native TSP was shown to exhibit a strong tendency to self-aggregation 6~6 when dispersed in aqueous solvents. These aggregates consist of lateral assemblies of single
Polysaccharide strands, showing a behavior that could be well described by the wormlike chain (D’Amico M 1999) or the Kuhns model. Static light scattering data on these particles shows that their stiffness is determined by the number of aggregated strands.
The ratio, glu: xyl: gal is 4:3: 1- 1.5 which is somewhat like a cell- wall polysaccharide, though it is a reserve polysaccharide. Thus tamarind polysaccharide is regarded as a galactoxyloglucan. High degree of substitution of glucan chain, produce a stiff, extended conformation for tamarind polysaccharide molecule, with large volume occupancy in solution.
4. General Properties Of TSP
Purified TSP is a high-molecular-weight, non-ionic, neutral, branched polysaccharide consisting of a cellulose-like backbone that carries xylose and galactoxylose substituents, (Saettone M. F. et al. 1997) chemical residues similar to that of mucin MUC-1 and episialin.(Hilkens J 1992) It is insoluble in organic solvents and dispersible in hot water to form a highly viscous gel such as a mucilaginous solution with a broad pH tolerance and adhesivity (Rao, PS. et al. 1946; Khanna M et al. 1997; Kulkarni D et al. 1997). In addition, it is nontoxic and nonirritant with haemostatic activity (Khanna M et al. 1997). It had been previously used in some drug formulations (Kulkarni D et al. 1997; S Sumathi and Ray AR 2002).
It is a galactoxyloglucan, belongs to the xyloglucan family possesses properties like Non-Newtonian rheologic behavior, Ferning pattern similar to natural tear film, Mucomimetic, mucoadhesive, pseudoplastic properties, as a viscosity enhancer with mucomimetic activity. (Saettone M F et al. 1997; Rolando M and Valente C 2007)
5. Pharmaceutical Uses Of TSP
Recently important properties of TSP have been identified. They include noncarcinogenicity (Sano M et al. 1996) mucoadhesivity, biocompatibility (Burgalassi S et al. 1996), and high drug holding capacity (Kulkarni D et al. 1997). These led to its application as excipient in hydrophilic drug delivery system (Burgalassi S et al. 1996 and Kulkarni D et al. 1997). Since TSP is an important excipient, the present study was undertaken to elucidate release kinetics of both water-soluble and water insoluble drugs from this matrix and high thermal stability (Saettone MF et al. 1997). It is used as binder in tablets, gelling agent, thickening agent, as emulsifier and as stabilizer in food, and pharmaceutical industries. Due to its hydrophilic and mucoadhesive property, it can be used in mucoadhesive drug delivery system (Burgalassiet S et al., 1996; Kulkarni D et al. 1998; D’Amico M et al. 1999).
The various applications of tamarind seed xyloglucan include thickening sauce, ice cream, dressing and processed vegetables. Tamarind seed xyloglucan is expected to find new food applications, serving as a thickener and stabilizer, gelling agent, ice crystal stabilizer and starch modifier, etc. It is called ‘ageing free starch’ because its property is similar to starch but is more stable (Shirakawa M and Yamatoya 2003).
Polysaccharides extracted from Tamarind seeds are known to produce gels in presence of sugar over a wide pH range. Thus, said polysaccharides are used as fruit pectin substitute in the production of jams, jellies and marmalades and as stabilizer for ice cream and mayonnaise (Gilles Pauly 1999).
TSP is an interesting candidate for pharmaceutical use, e.g. as a carrier of a variety of drugs for controlled release applications. Many techniques have been used to manufacture the TSP-based delivery systems (Table 1) which make TSP an exciting and promising excipient for the pharmaceutical industry for present and future applications.
1. Terbutaline sulphate Tablet
As a binder for tablet prepared by wet granulation and direct compression methods
It can be used as binder as well as polymer for sustained release formulations of low drug loading
Kulkarni D 1998
2. Diclofenac sodium Spheroids
Polysaccharide hydrogel was used as release modifier
Formulation follow zero order release pattern over 8 hrs with improved extent of absorption and bioavailability
Kulkarni GT 2005
3. Tablet (water soluble & water insoluble drugs)
As a carrier polysaccharide
Anomalous release of water soluble drugs
Zero order drug release for water insoluble drugs
Sumathi S & Ray AR 2002
4. Caffeine tablet
As a carrier polysaccharide
Anomalous drug release
Sumathi S & Ray AR 2003
TSP, a novel mucoadhesive polymer, cab be used as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics (Ghelardi E et al. 2000).
Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.
Eye drops made from tamarind seeds may be a treatment for dry eye syndrome.
Tamarind seed polysaccharide is adhesive, enabling it to stick to the surface of the eye longer than other eye preparations. Tamarind seed polysaccharide is used as an ingredient in food material and in pharmaceutical products (Rolando M and Valente C 2007). TSP possesses mucomimetic, mucoadhesive and pseudoplastic properties. TheTamarind seed polysaccharide eye drops performed as well as the hyaluronic acid drops on several measures of dry eye syndrome. Furthermore, the Tamarind seed polysaccharide drops did a significantly better job of relieving several key subjective symptoms of dry eye syndrome - namely, trouble blinking, ocular burning, and the sensation of having something in one's eye.
Tamarind seed polysaccharide (TSP) has high viscosity and mucoadhesive properties which make it a suitable candidate for addition to ophthalmic solutions of –β adrenergic blockers to increase the residence time on the cornea. The effect of an ophthalmic preparation containing timolol and TSP on intraocular pressure (IOP) was evaluated in rabbits.
TSP has a promising pharmaceutical uses and is presently under research as a carrier material in colon-specific drug delivery systems. The potential of TSP as a carrier for colonic drug delivery was demonstrated (Mishra MU and Khandare JN 2007). They prepare matrix tablets by wet granulation method using Ibuprofen as a model drug. Invitro drug release studies under conditions mimicking mouth to colon transit demonstrated the ability of TSP to release the drug in pH 6.8 Sorensen’s phosphate buffer with Rat caecal contents. The 4 % w/v rat caecal contents after 7 days of enzyme induction degraded TSP remarkably, thus it can be concluded that TSP may be used as a carrier for colonic drug delivery.
Besides the above proposed pharmaceutical uses of tamarind gum, the fact that the said gum has been used since long time as food additive is a good evidence of its lack of toxicity, also towards the ocular tissues. (Noda T et al. 1988)
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Mr. Rajendra Kotadiya
Lecturer, Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar, Gujarat, India.
Email: firstname.lastname@example.org, Mob. +919427529509
A. R. College of Pharmacy, New Vallabh Vidyanagar, Gujarat, India
Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar, Gujarat, India