In vitro

PURPOSE: The objective of the present study is to develop colon targeted drug delivery systems for sennosides using guar gum as a carrier. METHODS: Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for content uniformity and in vitro drug release study as per BP method. T50 % value from the dissolution studies was taken for selecting the best formulation. RESULTS: Guar gum matrix tablets released 4-18% sennosides in the physiological environment of gastrointestinal tract depending on the proportion of the guar gum used in the formulation. The matrix tablets containing 50% of guar gum were found to be suitable for targeting of sennosides for local action in the colon. Compared to tablets having 30% and 40% of guar gum, those with 50% guar gum gave better T50% (11.7 h) le and fewer amounts (5-8%) of drug release in upper GIT. These tablets with 50% guar gum released 43% and 96% sennosides with and without rat caecal fluids. This suggests the susceptibility of matrix to the colonic micro flora. The similarity factor (f2 value) for drug release with and without rat caecal fluids was found to be less than 30. When hydroxy propyl methylcellulose phthalate (10%) was used as a coat material on the matrix tablets, the initial loss of 58% sennosides in stomach could be completely averted. These tablets showed no change in physical appearance, content and dissolution profile upon storage at 45°C / 75% relative humidity for 3 months. CONCLUSION: The results of our study indicates that matrix tablets containing 50% guar gum and coated with 10% hydroxy propyl methylcellulose phthalate are most suitable for drugs like sennosides which are mainly active in the lower GIT. INTRODUCTION Several polysaccharides like, pectin and its salts, chondroitin sulphate, amylose and guar gum are being investigated as carriers for colon specific drug delivery. In pharmaceutical formulations, guar gum is used as a binder, disintegrant, suspending agent, thickening agent and stabilizing agent. (1,2) Guar gum and pectin are reported to be potential carriers for colon specific drug delivery. Colon specific drug delivery systems for 5-ASA and mebendazol have been developed using guar gum as a carrier (3,4). Guar gum in the form either of a matrix tablet or as a compression coat over a core tablet of drug is reported to target the drug to colon (5-9). The guar gum matrix tablets of albendazole 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 formulations to the rat caecal contents. Compression coated tablets of 5-ASA and matrix tablets of mebendazole have been prepared using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for drug content uniformity, and were subjected to in vitro drug release studies. The results of the study revealed that matrix tablets containing either 20% or 30% of guar gum are most likely to provide targeting of mebendazole for local action in the colon. A novel colonspecific drug delivery system based on guar gum matrix tablets was evaluated by conducting gamma scintigraphy studies using technitium-99m-DTPA as a tracer, in six healthy male human volunteers. Scintigraphs taken at regular intervals showed that some amount of tracer present on the surface of the tablets was released in stomach and small intestine and the bulk of the tracer present in the tablet mass delivered to the colon. These studies have shown the drug release retarding property of guar gum in the upper GIT and its degradation by the anaerobic bacteria in the colon (10-11).