Regular ArticleThe drug delivery to the colon has value not only in the colonic diseases such as ulcerative colitis, Crohn's diseases, inflammatory bowel disease, colorectal cancer but also improving oral delivery of peptides and other drugs degraded in the upper gastro-intestinal (GI) tract because of the less hostile environment prevailing in the colon compared with the stomach and small intestine. Colonic drug delivery is also useful to improve treatment of diseases depends on diurnal rhythm such as asthma and arthritis.1-3) The approaches utilized in achieving colonic delivery of drugs include use of prodrugs, 4) pH-sensitive polymer coating 5) and time-dependent formulations.6) In addition, the use of biodegradable polymers such as azo-polymer and polysaccharide (e.g. pectin and dextrin) for colon targeting are also reported in the literature. 7,8) Among the different approaches to achieve colon-selective drug delivery, the use of polymers, specifically biodegraded by colonic bacteria, holds great promise. The pH-dependent systems exploit the generally accepted view that pH of human GI tract increases progressively from the stomach (pH 2-3), small intestine (pH 6.5-7.0) to colon (7.0 to 8.0).2) Most commonly used pH-dependent coating polymers are methacrylic acid copolymer (i.e. Eudragit L100-55, Eudragit L100 and Eudragit S100), which dissolve at pH 5.5, 6.0 and 7.0, respectively. There are several polysaccharides naturally occurring in plant (e.g. pectin, guar gum, inulin), animal (e.g. chitosan, chondroitin sulfate), algae (e.g. alginates), or microbial (e.g. dextran) origin were studied for colon targeting.
9)Guar gum is a naturally occurring polysaccharide obtained from the seeds of two leguminous herbs, Cyamopsis tetragonolobus and Pasoraloides.10) It consists linear chains of (1→4)-b-D-manopyranosyl units with a-D-galactopyranosyl units attached by (1→6) linkages.11) It is hydrophilic in nature and swells in cold water forming viscous colloidal dispersions or sols.12) This gelling property retards release of the drug from the dosage form as well as it is susceptible to degradation in the colonic environment. The pH of 1% w/v aqueous dispersion varies from 5 to 7 and it is stable over wide pH range. It is non-ionic and hence the viscosity of dispersion is unaffected by pH and remain same in both acidic and alkaline medium. In the pharmaceutical formulations, guar gum is used as a binder, disintegrant, suspending agent, thickening agent and stabilizing agent.13) Guar gum was found to be a colon-specific drug carrier in the form of matrix and compression coated tablets, [13][14][15] microspheres, 9,16) and hydrogels. 17,18) The circadian timing system has a powerful influence on the regulation of sleep-wake state and recent evidence suggests that it can also affect the respiratory control system. This has led to the suggestion that the circadian timing system may influence the occurrence or severity of some types of sleep-related breathing disorders.19) The role of circadian rhythms in the pathoge...