NOVEL APPROACHES FOR COLON SPECIFIC DRUG DELIVERY The colon is advisable site where both local or systemic drug delivery can be achieved. The topical treatment of inflammatory bowel disease includes ulcerative colitis or Crohn's disease, Intestinal bowel syndrome (IBD) etc.Colon specific drug delivery is having capability to protect the drug from the acidic environment and the release of drug is only possible at the colonic environment. The use of hydrophilic gums which degrade in the colon helps in release of drug from the formulation. The colon is believed to bean absorption site for proteins and peptide drugs and protects them from the enzymatic degradation in duodenum and jejunum. Among all the routes being used, Oral route is preferable route for colon specific drug delivery. The colon has a long retention time and appears highly responsive to agents that enhance the absorption of poorly absorbed drugs. To achieve the successful colon drug delivery a drug need to be protected from the environment of upper GIT. Colon drug delivery requires longer release periods and slower release rates, which can be achieved by the application of conventional enteric coating and by use of slow release matrices1
. Approaches for CDDS1: 1. PH sensitive polymer coated drug delivery to colon 2. Delayed drug release drug delivery to colon 3. Microbially triggered drug delivery to colon 4. Prodrug approach for drug delivery to colon Novel Approaches2; 1. Pressure controlled drug delivery systems 2. Osmotic controlled drug delivery 3. Novel colon targeted delivery system (CODESTM) 4. Multiparticulate systems Pressure controlled drug delivery systems3Takya et.al, developed pressure controlled drug delivery, where the release of drug takes place as a result of peristalsis.It is the pressure difference makes the release of the drug only at the site of colon, as low pressure existing in the small intestine prevents the drug release. Here the drug is placed in the form of liquid into the ethyl cellulose capsules, whose thickness is the major factor for the disintegration. Osmotic controlled drug delivery4this technology developed by Alza Corporationis one of the approaches for achieving local and systemic absorption comprising enteric coating (prevent the release of drug in acidic media), a semi permeable membrane, a layer to delay drug release and core contains two compartments. The first compartment contains the active drug in any layer adjacent to exit passageway and the other is an osmopolymer composition to provide the osmotic push in the system.Semi permeable membranes are non-erodible in nature, but allow the passage of body fluids. Cellulose acylate and cellulose acetates forms the good semi permeable membranes. Delayed layer is made up of polyoxyethylene, present below the semipermeable membrane, delays the release of drug for about 2-4 hours. Osmopolymers including poly vinyl alcohol, poly vinyl pyrrolidine swells to push composition containing drug from the system. This system is utilized in the delivery of drugs for the treatment of colitis
, Crohn's disease and other conditions affecting the colon. Drug release begins when the unit reaches the colon. OROS-CT units can maintain a constant release rate for up to 24 h in the colon. Multiparticulate systems5 includes formulations in the form of pellets, granules, micro particles and nanoparticles4.Hardy and co-workers developed multiparticulate systems enabling the drug to reach the colon quickly and were retained in the ascending colon for a relatively long period of time. The system can pass easily through GIT, because of smaller size. The multiparticulate systems perform better in vivo performancethan single unit systems, as they spread throughout the length of the intestine causing less irritation, develop a slower transit through the colon and give a more reproducible drug release. a) PH- and time- dependent systems: A multiparticulate dosage from was prepared to deliver active molecules to colonic region, which combines pH dependent and controlled drug release properties. Enteric coating has traditionally been used to prevent drug release in the upper GI tract. Enteric coating polymers are reported to have been used as both binders and as coating materials for granules. Most commonly used pH-dependent coating polymers for pre oral delivery are methacrylic acid copolymers, Eudragit L100 and Eudragit S100, which dissolve at pH 6.0 and 7.0 respectively. b) Microbially controlled systems6: Natural hydrophilic polymers includes chondroitin sulphate, guar gum, pectin and dextran are commonly useful in this system, which all under goes microbial degradation at colonic environment where the site is rich of microbial load. The microbeads were prepared using gums bycross linking with the various divalent and trivalent cationic solutions. This makes the reduction of enormous swelling and prolongs the release of drug from the formulation. The conventional technique of ionotropic gelation was used to obtain drug loaded beads. c) Nano particulate systems Nano size colloidal carriers, are prepared with the natural and synthetic polymers, are get accumulated at the site of colon, and are responsible for providing the local activity (IBD, Colitis).
This accumulation at the site provides long residence time at the desirable area5. During inflammation at colon a strong immune response takes place by release of neutrophils and macrophages.Nano particulates are taken up by these macrophages and provide the response. Drug loaded nano carriers can be entrapped in to the PH sensitive microspheres which prevents the leakage of drug at upper parts of GIT. Novel colon targeted delivery system (CODESTM): CODESTMis a unique CDDS technology was designed to avoid the inherent problems associated with pH or time dependent systems. CODESTM is a combined approach of both pH dependent and microbial triggered CDDS. It has been developed by utilizing a unique mechanism involving lactulose, which acts as a trigger for site specific drug release in the colon.The system consists of a traditional tablet core containing lactulose, which is over coated with an acid soluble material, Eudragit E, and then subsequently over coated with an enteric material, Eudragit L. The premise of the technology is that the enteric coating protects the tablet in the gastric environment and dissolves quickly following gastric emptying. The acid soluble material coating protects the preparation as it passes through the alkaline pH of the small intestine.Once the tablet arrives in the colon, the bacteria enzymatically degrade the polysaccharide (lactulose) into organic acid8. Thus lowering the pH in the surrounding system is sufficient to affect the dissolution of the acid soluble coating and subsequent drug release. REFERENCES: 1. M.K. Chourasia, S.K.Jain "Pharmaceutical approaches to colon targeted drug delivery systems" J Pharm pharmaceutical Sci 6(1): 33-66, 2003. 2. Yang, L., Chu, J.S., Fix, J.A., Colon-specific drugdelivery: new approaches and in vitro/in vivoevaluation. Int J Pharm, 235:1-15, 2002. 3. Chien YW.Oral drug delivery and delivery systems In: Chein YW, editor. Novel drug delivery systems. Newyork: Marcel Decker Inc:1992:139-196 4. Anil K.Philip, Betty Philip "Colon targeted drug delivery systems: A Review on Primary and Novel Approaches" Oman medical journal 2010 , volume 25,Issue 2,April 2010. 5. Laila Fatima Ali Asghar and Sajeev Chandran "Multiparticulate Formulation .Approach to Colon Specific DrugDelivery: Current Perspectives"J Pharm Pharmaceut Sci (3): 327-338, 2006. 6. V.R. Sinha , Rachna kumria " Polysachrides in colon-specific drug delivery " international journal of Pharmaceutics 224(2001) 19-38. 7. Vyas SP,Khar RK. Gastroretentive systems .In : Vyas SP, Khar RK, editors.Controlled drug delivery: concepts and advances: New Delhi: Vallabh Prakashan,2005:218-253. 8. Sateesh kumar vemula" Different approaches to design and evaluation of colonspecific drug delivery systems" intjournal of pharmacy technology2009.