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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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