Purpose. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides. To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper gastrointestinal tract (GIT) and then be abruptly released into the proximal colon, which is considered the optimum site for colon-tar- geted delivery of drugs. Colon targeting is naturally of value for the topical treatment of diseases of colon such as Chron's diseases, ulcerative colitis, colorectal cancer and amebiasis. Peptides, proteins, oligonucleotides and vac- cines pose potential candidature for colon targeted drug delivery. Methods. The various strategies for targeting orally administered drugs to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymers, formulation of timed released systems, exploita- tion of carriers that are degraded specifically by colonic bacteria, bioadhesive systems and osmotic controlled drug delivery systems. Various prodrugs (sulfasalazine, ipsala- zine, balsalazine and olsalazine) have been developed that are aimed to deliver 5-amino salicylic acid (5-ASA) for localized chemotherapy of inflammatory bowl disease (IBD). Microbially degradable polymers especially azo crosslinked polymers have been investigated for use in tar- geting of drugs to colon. Certain plant polysaccharides such as amylose, inulin, pectin and guar gum remains unaf- fected in the presence of gastrointestinal enzymes and pave the way for the formulation of colon targeted drug delivery systems. The concept of using pH as a rigger to release a drug in the colon is based on the pH conditions that vary continuously down the gastrointestinal tract. Times dependent drug delivery systems have been devel- oped that are based on the principle to prevent release of drug until 3-4 h after leaving the stomach. Redox sensitive polymers and bioadhesive systems have also been exploited to deliver the drugs into the colon. Results. The approach that is based on the formation of prodrug involves covalent linkage between drug and carrier. The type of linkage that is formed between drug and carrier would decide the triggering mechanism for the release of drug in colon. The presence of azo reductase enzymes play pivotal role in the release of drug from azo bond prodrugs while glycosidase activity of the colonic microflora is responsible for liberation of drugs from glycosidic pro- drugs. Release of drugs from azo polymer coated dosage forms is supposed to take place after reduction and thus cleavage of the azo bonds by the azoreductase enzymes present in the colonic microflora. Natural polysaccharides have been used as tools to deliver the drugs specifically to the colon. These polysaccharides remain intact in the phys- iological environment of stomach and small intestine but once the dosage form enters into colon, it is acted upon by polysaccharidases, which degrades the polysaccharide and releases the drug into the vicinity of bioenvironment of colon. However, they should be protected while gaining entry into stomach and small intestine due to enormous swelling and hydrophilic properties of polysaccharides. This has been achieved either by chemical crosslinking or by addition of a protective coat. Formulation coated with enteric polymers releases drug when pH move towards alkaline range while as the multicoated formulation passes the stomach, the drug is released after a lag time of 3-5 h that is equivalent to small intestinal transit time. Drug coated with a bioadhesive polymer that selectively provides adhesion to the colonic mucosa may release drug in the colon. Conclusions. Improved drug delivery systems are required for drugs currently in use to treat localized dis- eases of the colon. The advantages of targeting drugs spe- cifically to the diseased colon are reduced incidence of systemic side effects, lower dose of drug, supply of the drug to the biophase only when it is required and mainte- nance of the drug in its intact form as close as possible to the target site.

/pdf/pharmaceutical-approaches-to-colon-targeted-drug-delivery-12fbefipbo.pdf

Pharmaceutical approaches to colon targeted drug delivery systems.

Pharmaceutical applications of various natural gums, mucilages and their modified forms

Guar gum as a promising starting material for diverse applications: A review.

Modified gums: Approaches and applications in drug delivery

New oral delivery systems for treatment of inflammatory bowel disease.

Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis.

PURPOSE: The present investigation is to study the influence of metronidazole and tinidazole on the usefulness of guar gum, a colon-specific drug car- rier based on the metabolic activity of colonic bacteria, using matrix tablets of albendazole (containing 20% of guar gum) as a model formulation. METHODS: The matrix tablets of albendazole were subjected to in vitro drug release studies in simulated colonic fluids (4%w/v of rat caecal contents) obtained after oral treatment of rats for 7 days either with varying doses of metronida- zole/ tinidazole and 1 mL of 2%w/v of guar gum or with 1 mL of 2%w/v of guar gum alone (control study) after completing the dissolution study in 0.1 M HCl (2 h) and pH 7.4 Sorensen's phosphate buffer (3 h). RESULTS: The guar gum matrix tablets of albenda- zole were found degraded by colonic bacteria of rat caecal contents and released about 44% of albendazole in simulated colonic fluids (control study) at the end of 24 h indicating the susceptibility of the guar gum for- mulations to the rat caecal contents. However, the release of albendazole decreased when the drug release studies were carried out in caecal contents of rats treated for 7 days with either metronidazole (10-50 mg/ kg once daily) or tinidazole (10-30 mg/ kg once daily), and the release of albendazole from the matrix tablets was found to be dose dependent. The release of the drug from guar gum formulations was found to increase with a decrease in the dose of metronidazole/ tinidazole administered. The antimicrobial activity of metronidazole/ tinidazole against the anaerobic bacte- ria of the rat's GI flora might have been inhibited to a varying degree depending on the dose of metronida- zole/tinidazole administered. CONCLUSIONS: The results of the study showed that concomitant adminis- tration of either metronidazole or tinidazole with guar gum based colon-specific drug delivery systems may interfere with the targeting of drugs to colon.

https://sites.ualberta.ca/~csps/JPPS4(3)/Y.Krishnaiah/guargum.pdf

Guar gum as a carrier for colon specific delivery; influence of metronidazole and tinidazole on in vitro release of albendazole from guar gum matrix tablets.

P.R. Bhaskar Reddy

Papers

Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis.

Guar gum as a carrier for colon specific delivery; influence of metronidazole and tinidazole on in vitro release of albendazole from guar gum matrix tablets.