Colon-specific drug delivery systems(CDDS)

Presented by
Anup D. Ganore M. pharm. (first sem.) Dept. of pharmaceutics

Guided By
Dr. Atish. S. Mundada

SSDJ college of pharmacy, chandwad

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Introduction Advantages Anatomy and physiology of colon Disorders of colon Colonic drug absorption and factors affecting Drug candidates for CDDS Approaches to CDDS Evaluation of CDDS Marketed drug product for the treatment of IBD. Conclusion Reference

Content

INTRODUCTION
The colon drug delivery has a number of important implications in the field of pharmacotherapy. Various diseases including inflammatory bowel diseases can be effectively treated by the local delivery of drugs to the large intestine. The treatment of IBD with antiinflammatory drugs is particularly improved by their local delivery to the bowel. by this technique absorption of the drugs from the stomach and small intestine can be minimized until the drug reaches the large intestine. The colon is a site where both local and systemic delivery of drugs can take place. 3

ADVANTAGES
Drug directly available at target site. Decreased dose to be administered. Decreased side effect. Improved drug utilization The colon is believed to be a suitable absorption site for peptides and protein drugs.
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ANATOMY AND PHYSIOLOGY OF COLON

Ascending colon

Transverse colon
Descending colon Sigmoid colon
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pH sensitive systems
pH

GI tract segment
stomach Small intestine Fasted condition:1.2-2 Fed condition:3.0-5.0 Jejunum:5.0-6.5 Ileum:6.0-7.5

Large intestine Rectum

Right colon:6.4 Mid and left colon:6.0-7.0 7.8-8.0

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THE TRANSIT TIME OF DOSAGE FORMS IN GI TRACT

Organ Transit time (hr)

Stomach

<1(fasting) >3(fed) 3-4

20-30
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Small intestine
Large intestine

DIS-ORDETS OF COLON

ULCERATIVE COLITIS INFLAMMATORY BOWEL DESEASES

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CROHS DESEASE

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METHOD FOR STUDYING COLONIC DRUG ABSORPTION

In vitro approaches, using isolated colonic epithelial cells or colonic tissue, have been used to study the role of physical and enzymatic barriers in colonic drug absorption. In vivo method for the assessment of colonic drug absorption have been set up in a variety of animal models including the 11 rat, the dog, and the pig.

FACTORS GOVERNING THE COLON DRUG DELIVERY

Physiological factors
Gastrointestinal transit Small intestinal transit Colon transit Gastric emptying Stomach and intestinal pH Colon microflora and enzymes Colonic absorption Gastrointestinal disease state

Pharmaceuticals factor
Drug candidates Drug carriers

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DRUG CANDIDAES FOR COLONIC DRUG DELIVERY

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APPROACHES TO COLON SPECIFIC DRUG DELIVERY

Coating with pH dependent polymers.
Covalent linkage of a drug with carrier. Azo conjugates Cyclodextrin conjugates Glycoside conjugates

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 Delivery system based on the metabolic activity of colonic bacteria. Coating with bio-degradable polymer Polymeric prodrug Hydrogel Polysaccharides as carriers Time released dosage form

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1.) COATING WITH pH DEPENDENT POLYMERS

In these systems, drugs are formulated into solid dosage forms such as tablets, capsules and pallets and coated with pH sensitive polymers as in enteric coating. Polymers are methacrylic resins (Eudragits). Eudragit available in two form Eudragit L and S
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2.) Covalent linkage of drug with carriers

AZO CONJUGATES (Azad khan,1982)

Hydrolysis of sulfasalazine(i) in to 5- amino salicylic acid(ii 17 and sulfapyridine(iii)

CYCLODEXTRIN CONJUGATES Cyclodextrine are cyclic oligosaccharides having 6-8dextrose units linked through 1-4 bond
.

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GLYCOSIDE CONJUGATES(Friend,1992)

Dexomethasone-21-B-D-glucoside ( arrow show site of action of glycosidase)

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3.) DELIVERY SYSTEM BASED ON THE METABOLIC ACTIVITY OF COLONIC BACTERIA

Coating with bio-degradable polymers.
Colonic drug delivery systems based on biodegradable poly (ether-ester) azopolymers were developed by Kalalal in 1996. The azopolymers had poor film forming properties a pH Independent Eudragit polymers was mixed azopolymer to coat 20 ibuprofen capsules.

Polymeric prodrug

A well known colonspecific prodrug, sulfasalazine is used in the treatment of ulcerative colitis and crohns disease. Chemically, sulfasalazine is 5aminosalicylic acid(5-ASA) coupled with sulphapyridine by Polymeric prodrug containing 5-ASA conjugate covalently linked to poly(methyl vinyl ether) 21 azo-bonding.

and poly(1-vinyl-2-pyrrolidone co-maleic anhydride)

Hydrogels

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Polysaccharides as carriers

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4) TIMED-RELEASE DOSAGE FORMS

The basic principle involved in the systems is the release of drug from dosage form should be after a pre-determined lag time to deliver the drug at the right site of action at right time and in right amount (shweta, et.al,2006) Colon drug delivery systems of diclofenac sodium (DS) was developed using time dependent approach. In this diclofenac sodium tablets were coated with ethyl cellulose in ethanol solution cooling diethyl phthalate as a plasticizer an PEG 400 24 as channeling agent.

EVALUATION OF COLON SPECIFIC DRUG DELIVERY SYSTEMS

Colon targeted drug are evaluated by two method are as follows: Invitro models In vivo animal models
String technique Endoscope technique Gamma scintigraphy
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MARKETED DRUG PRODUCT FOR THE TREATMENT OF IBD

Drug Mesalamine Mesalamine Trade name Asacol Salofac Formulation Eudragit-S coated tab.(pH-7) Eudragit-L coated tab.(pH-6) Eudragit-L coated tablets Eudragit-L coated beads Dose 0.8-2.4 g/day 1.0-4.0 g/day 1.0-2.0 g/day 9 mg/day
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Mesalamine

Claversal Meszal Calitoflak Entocort

Budesonide

CONCLUSION
Investigation on colon-specific drug delivery systems revealed that some peptidal drugs could be effectively delivered to colon in order to improve their systemic absorption. Localized release and uptake of drugs in colon can be utilized for the effective treatment of IBD. The use of prodrugs based on azobond and gycosides conjugation.
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REFERENCE
Pharmaceutical approaches to colon targeted drug delivery systems. M.K. chourasia, S.K. jain,. S.P. Vyas, R.K. Khar, Controlled Drug Delivery, Concepts and Advances, Vallabh Prakashan, P.No.218-253 N.K. Jain, Advances in Controlled and Novel Drug Delivery, CBS publication and distributors, 2001. P.No.89-110 Y.P. Reddy, J.R. Sowmya C. , Sree Lekha M. and Krishnaveni Y., Polymers in Colon Drug Targeting indian drug 47(3),2010,5-13

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