IN-VITRO AND IN-VIVO RELEASE STUDIES FROM ENTERIC COATED DRUG DELIVERY SYSTEMS UTILIZING MICROBIAL TRIGGERED BIODEGRADABLE GUAR GUM POLYSACCHARIDES FOR COLON SPECIFIC TARGETING

Abstract

The present study extensively investigated the colon as an effective drug delivery site for local colorectal cancer treatment using 5-Fluorouracil (5-FU) as model drug based on oral pulsatile release technology. Formulations coated with enteric Eudragit-S100 (EdâS-100) and swellable hydroxyl propyl methyl cellulose (HPMC) to a varying coat thickness of 2:4, 4:2, 3:4 and 4:3, were tested for in-vitro drug dissolution with various simulated fluids of stomach (pH 1.2), small intestine (pH 7.2) and colon (pH 6.8). Guar gum was used as matrix vehicle aimed to delay drug dissolutions and localize in the distal portions of small bowl or colon. The formulation was capable in delaying onset of drug dissolution for a programmed lag time period of 3-5 h in the hostile environment of upper gastrointestinal tract. The optimized enteric coated formulations containing 30% guar gum released only 5-12% approximately of 5-FU during 5 h dissolution studies in hostile physiological environment of stomach (pH 1.2) and small intestine (pH 7.2). The guar gum was found susceptible and encountered by colonic microfloras and released significant amount of 5-FU in simulated colonic fluids containing rat caecal contents (2 and 4% w/v) at the end of 24 h drug dissolution studies under anaerobic atmosphere. Furthermore, in -vivo studies were performed in order to examine the fate/ transit of formulations in gastrointestinal tract of albino rats, to validate the in-vitro methodology. However, these findings confirmed its applicability as a promising device for targeting of 5-FU at desirable site of colon.