Anup Ganore

7/30/2019 Anup Ganore

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Colon-specific drugdelivery systems(CDDS)

Presented byAnup D. Ganore

M. pharm. (first sem.)

Dept. of pharmaceutics

Guided ByDr. Atish. S. Mundada

SSDJ college of pharmacy,

chandwad


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ContentIntroduction

AdvantagesAnatomy and physiology of colon

Disorders of colon

Colonic drug absorption and factors

affectingDrug candidates for CDDS

Approaches to CDDS

Evaluation of CDDSMarketed drug product for the treatmentof IBD.

Conclusion

Reference


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INTRODUCTION

The colon drug delivery has a number of

important implications in the field ofpharmacotherapy. Various diseasesincluding inflammatory bowel diseases canbe effectively treated by the local deliveryof drugs to the large intestine.

The treatment of IBD with anti-inflammatory drugs is particularlyimproved by their local delivery to thebowel. by this technique absorption of the

drugs from the stomach and smallintestine can be minimized until the drugreaches the large intestine.

The colon is a site where both local and

systemic delivery of drugs can take place.


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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 suitableabsorption site for peptides and proteindrugs.


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Ascending colon

Transverse colon

Descending colon

Sigmoid colon

ANATOMY AND PHYSIOLOGY

OF COLON


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pH sensitive systems

GI tract segment

pH

stomach Fasted condition:1.2-2Fed condition:3.0-5.0

Small intestine Jejunum:5.0-6.5

Ileum:6.0-7.5

Large intestine Right colon:6.4

Mid and left colon:6.0-7.0

Rectum 7.8-8.0


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THE TRANSIT TIME OFDOSAGE FORMS IN GI

TRACT

Organ

Stomach

Small intestine

Large intestine

Transit time (hr)

3(fed)

3-4

20-30


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DIS-ORDETS OF COLON

INFLAMMATORY

BOWEL DESEASES

ULCERATIVE COLITIS


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CROHS DESEASE


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METHOD FOR STUDYINGCOLONIC DRUG

ABSORPTION

In vitro approaches, using isolated colonicepithelial cells or colonic tissue, have beenused to study the role of physical andenzymatic barriers in colonic drug

absorption.In vivo method for the assessment of

colonic drug absorption have been set upin a variety of animal models including the

rat, the dog, and the pig.


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FACTORS GOVERNING THECOLON DRUG DELIVERY

Physiologicalfactors Gastrointestinal

transit

Small intestinal transit Colon transit

Gastric emptying

Stomach andintestinal pH

Colon microflora andenzymes

Colonic absorption

Gastrointestinal

disease state

Pharmaceuticalsfactor

Drug candidates

Drug carriers


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DRUG CANDIDAES FORCOLONIC DRUG DELIVERY


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APPROACHES TO COLONSPECIFIC DRUG DELIVERY

Coating with pH dependent polymers.

Covalent linkage of a drug with carrier.

Azo conjugatesCyclodextrin conjugates

Glycoside conjugates


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Delivery system based on the metabolicactivity of colonic bacteria.

Coating with bio-degradable polymer

Polymeric prodrugHydrogel

Polysaccharides as carriers

Time released dosage form


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1.) COATING WITH pHDEPENDENT POLYMERS

In these systems, drugs are formulatedinto solid dosage forms such as tablets,capsules and pallets and coated with pHsensitive polymers as in enteric coating.

Polymers are methacrylic resins(Eudragits). Eudragit available in two formEudragit L and S


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2.) Covalent linkage ofdrug with carriers

AZO CONJUGATES (Azad khan,1982)

Hydrolysis of sulfasalazine(i) in to 5- amino salicylic acid(i

and sulfapyridine(iii)


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CYCLODEXTRIN CONJUGATESCyclodextrine are cyclic

oligosaccharides having 6-8-dextrose units linked through 1-4bond

.


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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 ONTHE METABOLIC ACTIVITY OF

COLONIC BACTERIA Coating with bio-degradable

polymers.

Colonic drug delivery systems based onbiodegradable poly (ether-ester)azopolymers were developed by Kalalal in

1996.The azopolymers had poor film forming

properties a pH Independent Eudragitpolymers was mixed azopolymer to coat

ibuprofen capsules.


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Polymeric prodrug

A well known colon-specific prodrug,sulfasalazine isused in thetreatment ofulcerative colitisand crohns

disease.Chemically,

sulfasalazine is 5-aminosalicylicacid(5-ASA)coupled withsulphapyridine by

azo-bonding.

Polymeric prodrug containing 5-ASA conjugate

covalently linked to poly(methyl vinyl ether)and poly(1-vinyl-2-pyrrolidone co-maleic anhydride)


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Hydrogels


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Polysaccharides as carriers


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4) TIMED-RELEASE DOSAGEFORMS

The basic principle involved in the systemsis the release of drug from dosage formshould be after a pre-determined lag timeto 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 diclofenacsodium (DS) was developed using time

dependent approach. In this diclofenacsodium tablets were coated with ethylcellulose in ethanol solution cooling di-ethyl phthalate as a plasticizer an PEG 400

as channeling agent.


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EVALUATION OF COLON

SPECIFIC DRUG DELIVERYSYSTEMS

Colon targeted drug are evaluated by twomethod are as follows:

Invitro modelsIn vivo animal models

String technique

Endoscope technique

Gamma scintigraphy


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MARKETED DRUG PRODUCTFOR THE TREATMENT OF IBD

Drug Tradename

Formulation Dose

Mesalamine Asacol Eudragit-S coated

tab.(pH-7)

0.8-2.4

g/dayMesalamine Salofac Eudragit-L coated

tab.(pH-6)1.0-4.0g/day

Mesalamine Claversal

Meszal

Calitoflak

Eudragit-L coated

tablets

1.0-2.0

g/day

Budesonide Entocort Eudragit-L coatedbeads

9 mg/day


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CONCLUSION

Investigation on colon-specific drugdelivery systems revealed that somepeptidal drugs could be effectively

delivered to colon in order to improvetheir systemic absorption. Localizedrelease and uptake of drugs in colon canbe utilized for the effective treatment of

IBD. The use of prodrugs based onazobond and gycosides conjugation.


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REFERENCE

Pharmaceutical approaches to colon targeteddrug 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 DrugDelivery, 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 Targetingindian drug 47(3),2010,5-13


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