Tamarind Seed Polysaccharides : A Novel Carrier For Drug Delivery Systems

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Rajendra Kotadiya

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)

image

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-(14) 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-(16) linkage. One D-galactopyranosyl unit is attached to one of the xylopyranosyl unit through a ί-D-(12) 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.

Table 1

Dosage form

Applications

Comments

References

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

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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)

6. References:

  1. Burgalassi S et al. (1996) Development and in vitro/ in vivo testing of mucoadhesive buccal patches releasing benzydamine and lidocaine. Int J Pharm 133: 1-7.
  2. D’Amico M (1999) Effects of Timolol and of Timolol with Tamarind Seed Polysaccharide on Intraocular Pressure in Rabbits, Pharmacy and Pharmacology Communications 5(5): 361-364. doi: 10.1186/1471-2415-7-5.
  3. Gerard T, (1980) Tamarind Gum in Hand book of water soluble gums and resins. (Ed) R.L. Davidson, McGraw-Hill Book Co. USA 23. 12; 1-23.
  4. Ghelardi et al. (2000) Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits. Journal of Antimicrobial Chemotherapy 46: 831-834.
  5. Gidley MJ et al. (1991) Structural and solution properties of TSP. Carbohydrate Research 214: 299-314.
  6. Gilles Pauly (1999) Use of extract of Tamarind seeds rich in xyloglucan and cosmetic or Pharmaceutical product containing such extracts. US patent, 5,876,729
  7. Glicksman, M (1996) Tamarind seed gum, In: M. Glicksman (Ed.), Food Hydrocolloids, Volume III, CRC Press Inc., Boca Raton, Florida, USA, 191-202.
  8. Hilkens J et al. (1992) Cell membrane-associated mucins and their adhesion modulating property. Trends in Biochemical Sciences 17: 359–63.[ISI][Medline]
  9. Hulse, J (1996) Flavours, spices and edible gums: opportunities for integrated agroforestry systems, R.R.B. Leakey, A.B. Temu, M.Melnyk & P. Vantomme (eds.), Domestication and Commercialization of Non-timber Forest Products in Agroforestry Systems, Non-Wood Forest Products No. 9, FAO, Rome, Italy, 86-96.
  10. Khanna M et al. (1987) Standardisation of Tamarind seed polyose for Pharmaceutical use. Indian Drugs 24: 268-269.
  11. Khanna M et al. (1997) Polyose from seeds of Tamarindus indica of unique property and immense pharmaceutical use, in Trends in Carbohydrates Chemistry, vol-4; Surya internationalpublications, Dehra dun, India: 79-81.
  12. Kulkarni D et al. (1997) Tamarind seed polyose: A potential polysaccharide for sustained release of verapamil hydrochloride as a model drug. Indian J Pharm Sci, 59(1): 1-7.
  13. Kulkarni D et al. (1997) Tamarind seed polyose: A potential polysaccharide for sustained release of verapamil hydrochloride as a model drug. Indian J Pharm Sci 59(1): 1-7.
  14. Kulkarni D et al. (1998) Performance evaluation of tamarind seed polyose as a binder and in sustained release formulations of low drug loading 1: 50-53.
  15. Kulkarni G et al. (2005) Development of Controlled Release Spheriods using Natural Polysaccharide as Release Modifier. Drug Delivery 12(4): 201 – 206.
  16. Lang P et al. (1993) Investigations on the Solution Architecture of Carboxylated Tamarind Seed Polysaccharide by Static and Dynamic Light Scattering. Macromolecules 26: 3992-3998.
  17. Leakey RRB (1999) Potential for novel food products from agroforestry trees: A review. Food Chemistry 66: 1-14
  18. Meier H and Reid JSG (1982) Reserve Polysaccharides other than Starch in higher plants in Encyclopedia of Plant Phisiology, N.S.: Plant Carbohydtrates I: Intracellular Carbohydtrates, (Eds) FA Loewns and W. Tanner, Spriner-Verlag 134: 418-471.
  19. Mishra MU and Khandare JN. (2007) Tamarind Seed Polysaccharides: Biodegradable Polymer for Colonic Drug Delivery. Second International Conference and Indo-Canadian Satellite Symposium on Pharmaceutical Science, Technology, Practice and Natural Products, Conference Chronicle, DDS-35, pp206.
  20. Nandi RC et al. (1975) A Process for preparation of polyose from the seeds of Tamarindus indica, Ind. Pat. 142092.
  21. Noda T et al. (1988) Acute toxicity studies have been published, e.g., by in Seikatsu Eisei 32(3): 110-15.
  22. Rao PS and Srivastav HC (1973) Tamarind. In Indusrtial Gums, (Ed.) R.L. Whistler, Academic Press, 2nd Ed, New York, p. 369-411.
  23. Rao PS et al. (1946) Extraction and purification of tamarind seed polysaccharide. J Sci Ind Research (India) 4:705.
  24. Reid JSG & Edwards ME (1995) Food Polysaccharides and their Applications, Marcel Dekker Inc., New York, USA, 155-186
  25. Rolando M and Valente C (2007) Establishing the tolerability and performance of tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of a clinical study, BMC Ophthalmol 7: 5.
  26. Saettone MF et al. (1997) Ophthalmic solutions viscosified with tamarind seed polysaccharide. International patent application PCT/IT97/00026.
  27. Saettone MF et al. (1997) Ophthalmic solutions viscosified with tamarind seed polysaccharide, PCT Int. Appl. WO 97 28,787.
  28. Sano M et al. (1996) Lack of carcinogenicity of tamarind seed polysaccharide in B6C3F mice, Food and Chem Toxicol 34: 463-467.
  29. Shirakawa M. and Yamatoya K (2003) Xyloglucan: Its Structure and Function, Foods Food Ingredients J. Jpn. 208; 11.
  30. Sumathi S and Ray AR (2002) Release behavior of drugs from tamarind seed polysaccharides tablets, J Pharm Pharm Sci. 5(1): 12-18.
  31. Sumathi S and Ray AR (2003) Role of Modulating Factors on Release of Caffeine from Tamarind Seed Polysaccharides tablets. Trends Biomater. Artif. Organs. 17(1): 41-46.

About Authors:

Rajendra Kotadiya

Mr. Rajendra Kotadiya

Lecturer, Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar, Gujarat, India.
Email: rajlec_qa@yahoo.com, Mob. +919427529509

Vishnu Patel

A. R. College of Pharmacy, New Vallabh Vidyanagar, Gujarat, India

Harsha Patel

Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar, Gujarat, India

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