A delayed release system may be aimed for colon drug targeting. The colon targeted delivery of pharmaceutical drugs is important to achieve localized effect for the treatment of colonic diseases and/or systemic drug delivery for drugs absorbed from colon, for e.g. peptides and proteins.

This system is based on the degradation of the polymeric compression-coat by specific enzymes produced by entero-bacteria in the colon. Importance of microbial polysaccharidases in colon specific drug delivery of formulations containing polysaccharide excipients is beyond doubt. Present review presents a compilation of the important polysaccharide excipients, along with their metabolism in human colon, the mechanism of action of the degrading enzymes and genetic aspects of polysaccharide degrading colonic microflora shall help in the improvement in the field of colon targeting.


POLYSACCHARIDE EXCIPIENTS 

The microbial enzymes, β-D-glucosidase, β-D-galactosidase, amylase, pectinase, xylanase, β-D-xylosidase, dextranase and others ferment the coatings of drug core, embedding of the drug in biodegradable matrix and drug-sachharide conjugates (prodrugs). The polysaccharides used for the purpose include chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylase and locust bean gum. The compounds have to pass to the lower part of the gastrointestinal tract without being degraded in the upper parts as stomach, upper part of small intestine.

Microbially degradable polysaccharides containing glycosidic bonds that can be used as a coat are :
  • Alginates
  • Amylase
  • Arabinogalactan
  • Arabinoxylan
  • Cellulose
  • Chitosan
  • chondroitin sulfate
  • dextran
  • galactomannan (guar gum, locust bean gum)
  • inulin
  • karaya gum
  • laminarin
  • pectins
  • starch
  • tragacanth gum
  • xanthan gum
  • xylan
These polymers are characteristic in having large numbers of derivatizable groups, wide range of molecular weights, varying chemical compositions, low toxicity, biodegradability and high stability. They are also approved as pharmaceutical excipients.

The importance of gums and mucilages as pharmaceutical excipients, widely used natural materials, for conventional and novel dosage forms has been reviewed. These natural materials have advantages over synthetic ones since they are chemically inert, nontoxic, less expensive, biodegradable and widely available. The gums can be modified in different ways to obtain tailor-made materials for drug delivery systems and thus can compete with the available synthetic excipients.

Pectin can be extracted from low value agricultural wastes as pulp of sugar beets and citrus fruits. It was attempted to shift the focus of pectin application from food industry to one of the excipients of pharmaceutical industry. It was suggested that since pectin is efficiently degraded by colonic microflora, pectin derived matrix can be utilized for controlled as well as colon specific drug delivery.

The amide prodrug, chitosan-5-ASA did not release ASA in the cecal and colonic simulated fluids. The ester prodrugs, hydroxypropyl cellulose-5-ASA did not release the drug in any of the gastrointestinal contents of rats. Release of 5-ASA from cyclodextrins was higher in cecal and colonic contents as compared to stomach and small intestine. Thus, ester prodrugs with certain solubility could release 5-ASA in the cecal and colonic contents of rat.

The suitability of gaur gum is due to its high viscosity resulting from its high molecular weight (1,000,000) and long polysachharide chain. Each 100 gm gaurgum contains galactomanan 80, water 12, protein 5, acid soluble ash 2 and fat 0.7 g. It consists of high molecular weight hydrocolloidal polysaccharide, composed of galactan and mannan units, combined through glycosidic linkages and is degraded in the large intestine due the presence of microbial enzymes.

These excipients, directly or indirectly influence the extent and/or rate of drug release and absorption. Polysaccharides can be extracted from plants at relatively low cost and can be chemically modified to suit specific needs and are of variable physicochemical properties. Modified release dosage forms can be prepared in which many polysaccharide-rich plant materials are successfully used as matrix formers. Control drug release can be achieved with the help of some natural polysaccharides that show environmental-responsive gelation.

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