Original Article MULTIPARTICULATE DRUG DELIVERY SYSTEM FOR COLON TARGETING SANGEETA MOHANTY* 1 , AMIT KUMAR PANIGRAHI 2 1 Department of pharmaceutics, School of Pharmaceutical Sciences, Siksha ′ O′ Anusandhan University, Khandagiri Square, Bhubaneswar. Odisha 751003, 2 Received: 24 Jun 2014 Revised and Accepted: 20 Sep 2014 ABSTRACT Objective: The objective of the present investigation was to design a multi particulate delivery system for site-specific delivery of 5-aminosalicylic acid (ASA) using natural polysaccharides (pectin) and pH-sensitive polymer (Eudragit S100) for the treatment of ulcerative colitis. This system is anticipated to protect the drug loss in the upper GI tract, which results from the inherent property of Eudragit S100 (ES), and deliver ASA in the colon only. Methods: The use of enteric polymers (ES) as the protective coating on the microspheres makes them able to release the drug at the particular pH of colonic fluid. A combined mechanism of release is used, which combines specific biodegradability of polymer and pH-dependent drug release from the coated microspheres. The effects of polymer concentration, stirring rate, and concentration of emulsifier on particle size and drug loading were studied. Pectin microspheres were prepared by emulsion dehydration method using different ratios of drug and polymer (1:2 to 1:4), stirring speeds (1000-3000 rpm) and emulsifier concentrations (1%-3% wt/vol). Eudragit -coating of pectin microspheres was prepared by oil-in-oil solvent evaporation method. Both the pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, swell ability and In vitro drug release in pH progression media. Result: The release profile of 5-ASA from Eudragit-coated pectin microspheres was pH dependent. Hence, the drug released quickly at pH 7.5 but the release rate was much slower in acidic medium. Conclusion: The designed drug delivery system can be used as a tool for colon targeting of drugs. CPC India Pvt. Ltd, Ahmadabad. India Email: sangeetamohanty12@gmail.com Keywords: 5-Aminosalicylic acid, Colon targeting, Microspheres, Pectin. INTRODUCTION Biodegradable pectin microspheres offer a novel approach for developing sustained release drug delivery systems that have potential for colonic drug delivery. In the controlled release area, biodegradable microspheres are one of the most useful devices to deliver materials in an effective, prolonged and safe manner. Pectin, a hetero saccharide derived from the cell wall of plants used as a gelling agent for scanning purpose. The degradation of pectin occurs mainly in the colon by pectinolytic enzymes secreted by microorganisms. As a result pectin has increasingly gained acceptance as the carrier polymer for sustained release and site specific delivery dosage forms, such as beads, pellets, tablets, and films. [1,2]. For colonic delivery of drugs, different approaches include the use of prodrugs, [3,4] pH-sensitive polymer coating, [5,6]and time-dependent formulations [7,8]. In addition, the use of biodegradable polymers such as azopolymer and polysaccharide (e. g., Pectin and Dextran) for colon targeting are also reported in the literature.[9,10]. Among the different approaches to achieve colon- target drug delivery, the use of polymers, specifically biodegraded by colonic bacteria, proves better results. The pH-dependent systems exploit the generally accepted view that pH of the human GI tract increases progressively from the stomach (pH 2-3) to the small intestine (pH 6.5-7.0) to the colon (7.0-8.0),[11]. Most commonly used pH-dependent coating polymers are meth acrylic acid copolymer (i. e., Eudragit L100-55, Eudragit L100, and Eudragit S100), which dissolve at pH 5.5, 6.0, and 7.0, respectively. Pectin is a predominately linear polymer of mainly α-(1-4)-linked D- galacturonic acid residues interrupted by 1, 2-linkedL-rhamnase residues. Pectin has a few hundred to about 1000building blocks per molecule. As pectin is soluble in water, it is not able to shield its drug load effectively during its passage through the stomach and small intestine. Hydrophilic polymer matrix systems are widely used in oral controlled drug delivery because of their flexibility to obtain a desirable drug release profile, cost-effectiveness, and broad regulatory acceptance,[12,13]. The ability of the hydrophilic polymer matrices to release an entrapped drug in aqueous medium and to regulate the release of such drug by control of swelling and cross- linking makes them particularly suitable for controlled-release applications,[14]. These matrices can be applied for the release of both hydrophilic and hydrophobic drugs and charged solutes. 5-ASA is a drug used for treating ulcerative colitis. The exact mechanism of 5-ASA is not known but is believed to reduce inflammation in the The 5-ASA was a gift from S. A. Pharma (Saga r, India), pectin (Sigma-Aldrich) and Eudragit S-100 (Rohm, GmbH, Germany) were obtained from Alembic Ltd (Gujarat, India). Glutaraldehyde, castor oil and Magnesium Chloride were procured from Hi- media, India. Hydrochloric Acid procured from Qualigens Fine chemicals, India. Isopropyl alcohol, HPLC grade methanol and water was obtained colon. Ulcerative colitis and other inflammatory diseases cause excessive production of chemicals, for example, prostaglandins, that produce inflammation in the colon. Prostaglandins are produced by the enzymes, cyclooxygenase and lipoxygenase. These enzymes are over-active in individuals with ulcerative colitis. 5-ASA may work by blocking the activity of cyclooxygenase and lipoxygenase, thereby, reducing the production of prostaglandins. Reduced production of prostaglandins decreases inflammation in the colon and the symptoms associated with ulcerative colitis. Site-specific delivery of 5-ASA may reduce the systemic side effects and provide effective and safe therapy that may reduce the dose and duration of therapy when compared with the conventional treatment. Microspheres of Eudragit S100 were developed for delivery of 5- Aminosalicylic acid specifically into the colon. This type of advanced pharmaceutical dosage forms (Multi particulate systems) is of great practical importance for instance, for the treatment of ulcerative colitis. The present investigation reveals that Eudragit-coated pectin microspheres are promising controlled release carriers for colon- targeted delivery of 5-ASA. MATERIALS AND METHODS International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 3, 2015 Innovare Academic Sciences