Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery
The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed , prolonged absorption time, decreased , and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. 1. Introduction In the recent times, colon-specific technologies have utilized single or combination of the following primary approaches, with varying degrees of success: (1) pH-dependent systems, (2) time-dependent systems, (3) prodrugs, and (4) colonic microflora-activated systems [1, 2]. Among the different approaches to achieve colon specific drug delivery system, the use of polymers specifically degraded by colonic bacterial enzymes (such as β-glucoronidase, β-xylosidase, β-galactosidase, and azoreductase) holds promise. Microbially activated delivery systems for colon targeting are being developed to exploit the potential of the specific nature of diverse and luxuriant microbiota associated with the colon compared to other parts of the gastrointestinal (GI) tract. These colonic microbiotas produce a large number of hydrolytic and reductive enzymes which can potentially be utilized for colonic delivery [1, 2]. Most of these systems are based on the fact that anaerobic bacteria in the colon are able to recognize the various substrates and degrade them with their enzymes. Natural gums are often preferred to synthetic materials due to their low-toxicity, low-cost, and easy availability. A number of colon-targeted delivery systems based both on combination of pH, polysaccharides
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