Colon – Specific Drug Delivery SystemColon – Specific Drug Delivery System

CONTENTS•IntroductionIntroduction•Anatomy & Physiology of Colon•Factors governing the colon drug delivery•Colon absorption•The major functionsThe major functions•AdvantagesAdvantages•Pharmaceutical Approaches for Targeting Drugs to Colon•Platform Technologies for CTDDS•Evaluation•Conclusion

Introduction:

Colon as a site for drug delivery.

Colon was considered as BLACK-BOX as most of the

drugs are absorbed from upper part of the GI tract.

The site specific delivery of drugs to lower parts of the GIT

is advantage for localized treatment of several colonic

diseases(IDB).

The CDDS drug release and absorption should not occur in

the stomach as well as small intestine, but only released and

absorbed once the system reaches to the colon.

Why is CDDS needed?Why is CDDS needed?

Ensure direct treatment at the disease site.

Lower dosing and less side effects.

Beneficial in the treatment of colon diseases.

Suitable absorption site for protein and peptide

drugs.

Used to prolong the drug therapy.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Anatomy & Physiology of Colon

GIT: •Stomach•Small intestine•Large intestineCOLON:

Colon Rectum

Anal canal

Colon consists:• Cecum• Ascending colon• Transverse colon• Descending colon• Sigmoid colon

B R Nahata College of Pharmacy Mandsaur (M.P.)

•Serosa

•Muscularis

externa

•Submucosa

•mucosa

Layers:

B R Nahata College of Pharmacy Mandsaur (M.P.)

B R Nahata College of Pharmacy Mandsaur (M.P.)

Factors governing the colon drug delivery

Gastrointestinal transit

Small intestinal transit

Colonic transit

Gastric emptying

Stomach and intestinal pH

Colonic micro flora and enzymes

B R Nahata College of Pharmacy Mandsaur (M.P.)

pH of GIT:pH of GIT:LOCATION Ph

1.STOMACH:

Fasted

Fed

1.5-2.0

3.0-5.0

5.0-6.5

2.SMALL INTESTINE:

Jejunum

Ileum

6.0-7.5

6.4

6.7-7.3

3.LARGE INTESTINE:

Right colon

Mid colon

Left colon

6.5-7.0

6.6-7.0

6.6

7.0B R Nahata College of Pharmacy Mandsaur (M.P.)

Drug absorption in the colonDrug absorption in the colon

Drug molecules pass from the apical to

basolateral surface of the epithelial cell by

1. Transcellular - Passing through colonocytes.

2. paracellular - Passing between adjacent

colonocytes.

B R Nahata College of Pharmacy Mandsaur (M.P.)

The major functions The major functions

The absorptive capacity is very high; each day about 2000 ml of fluid enters the colon through the ileocecal valve from which more than 90% of the fluid is absorbed.

Creation of a suitable environment for the growth of colonic microorganisms, such as Bacteroides, Eubacterium, and Enterobacteriaceae.

Expulsion of the contents of the colon at a suitable time.

Absorption of water and Na+ from the lumen, concentrating the fecal content, and secretion of K+ ions

B R Nahata College of Pharmacy Mandsaur (M.P.)

AdvantagesDrugs are directly available at the target site.

Comparatively lesser amount of required dose.

Decreased side effects.

Improved drug utilization.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Pharmaceutical Approaches for Targeting Drugs to Colon

pH sensitive systemsMicrobially triggered system

◦Prodrugs ◦Polysaccharide based systems

Timed release systemsOsmotically controlled drug

delivery systemsPressure dependent release

systemsB R Nahata College of Pharmacy Mandsaur (M.P.)

pH sensitive systems

Solid formulations for colonic delivery that are based on pH-dependent drug release mechanism are similar to conventional enteric-coated formulations.

Utilize enteric polymers that have relatively higher threshold pH for dissolution.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Polymers

B R Nahata College of Pharmacy Mandsaur (M.P.)

Mechanism of actionMechanism of action

B R Nahata College of Pharmacy Mandsaur (M.P.)

Microbially Triggered Systems

Bacterial count in the colon is much higher around 1011-1012 CFU/ml.

400 species Fundamentally anaerobic in

nature. Predominant species:

Bacteroides, Bifidobacterium and Eubacterium.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Major metabolic processes occurring in the colon are hydrolysis and reduction

Enzymes in Colon

Reducing enzymes Hydrolytic enzymesNitroreductase EsterasesAzoreductase AmidasesN-oxide reductase GlycosidasesSulphoxide reductase GlucuronidaseHydrogenase Sulfatase

Azoreductases, which reduces azo-bonds selectively andPolysaccharidases which degrades the polysaccharides

.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Azobond prodrugs

Hydrolysis of sulphasalazine (i) into 5-aminosalicylic acid (ii) andsulfapyridine (iii).

B R Nahata College of Pharmacy Mandsaur (M.P.)

Glycoside conjugates

B R Nahata College of Pharmacy Mandsaur (M.P.)

Natural Polysaccharides as Polymer

for Colon Drug Delivery

Chitoson Pectin Guar gumChondroitin sulphateDextran Almond gum Locust bean gumCyclodextrins Inulin Boswellia gumKhaya gum

B R Nahata College of Pharmacy Mandsaur (M.P.)

Enteric-coated polysaccharide matrix

B R Nahata College of Pharmacy Mandsaur (M.P.)

Compression Coated Tablets

B R Nahata College of Pharmacy Mandsaur (M.P.)

Mixed Film Coated Tablets

B R Nahata College of Pharmacy Mandsaur (M.P.)

Timed Release Systems

Releases the drug after a predetermined lag time

The lag time usually starts after gastric emptying because most of the time- controlled formulations are enteric coated

Drug release from these systems is not pH dependent

B R Nahata College of Pharmacy Mandsaur (M.P.)

B R Nahata College of Pharmacy Mandsaur (M.P.)

Osmotically Controlled Drug Delivery Systems

Depend up on the osmotic pressure exerted by Dependosmogen on drug compartment with which though drug get released slowly though the orifice

Rigid semi permeable membraneOsmotic agent layer

Delivery port

Fluid to be pumped

B R Nahata College of Pharmacy Mandsaur (M.P.)

Pressure Dependent Release Systems

Relies on the relatively strong peristaltic waves

in the colon that lead to an increased luminal

pressure, in response to raised pressure of the

colon the dosage form get ruptured and release

the drug at desired site

B R Nahata College of Pharmacy Mandsaur (M.P.)

Platform Technologies for CTDDS

• PULSINCAP

• OROS-CT

• CODESTM

• CHRONOTROPIC® SYSTEM

B R Nahata College of Pharmacy Mandsaur (M.P.)

PULSINCAP

B R Nahata College of Pharmacy Mandsaur (M.P.)

OROS-CT

B R Nahata College of Pharmacy Mandsaur (M.P.)

CODESTM

B R Nahata College of Pharmacy Mandsaur (M.P.)

CHRONOTROPIC® SYSTEM

Drug containing core

HPMC Coat

Enteric coat

B R Nahata College of Pharmacy Mandsaur (M.P.)

EvaluationInvitro modelsInvitro test for intactness of coating and carriers in simulated

conditions of stomach and intestine

step1

Drug release study in 0.1N HCL for 2 hours (mean gastric emptying)

step 2

Drug release study in phosphate buffer for 3 hours (mean small intestine transit time)

B R Nahata College of Pharmacy Mandsaur (M.P.)

In vitro enzymatic degradation test

Method 1:

Drug release in buffer medium containing enzymes(e.g.pectinase, dextranase) or rat or guinea pig or rabbit decal contents

Amount of drug release in particular time directly proportional to the rate of degradation of polymer carrier.

Method 2:

Incubating carrier drug system in fermenter

Suitable medium containing colonic bacteria (streptococcus faecium or B.ovatus)

Amount of drug released at different time intervels determined.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Clinical evaluation of colon-specific drug delivery system

• Gamma Scintigraphy

• High-frequency capsule

B R Nahata College of Pharmacy Mandsaur (M.P.)

Gamma Scintigraphy showing the spread of the tracer allalong the ascending, transverse, descending and sigmoidcolon

B R Nahata College of Pharmacy Mandsaur (M.P.)

High-frequency capsule High-frequency capsule method:method:The relative BA of CDDS can be evaluated by high

frequency capsules smoth plastic capsule containing

small latex bollon, drug and radiotracer taken orally

Triggering system (high frequency generator)

Release of drug and radiotracerTriggered by an impules, the release is monitered

In different parts of GIT byRadiological localization

B R Nahata College of Pharmacy Mandsaur (M.P.)

Conclusion

The colonic region of the GIT has become an increasingly important site for drug delivery and absorption.

CDDS offers therapeutic benefits to patients in both local and systemic treatment.

Systems utilize natural materials that are degraded by colonic bacterial enzymes.

Colon provides favorable factors and conditions for designing of delivery systems.

High commercial viability. Increasing number of international patents and research work in this particular mode of drug delivery itself shows its potential for pharmaceutical market.

B R Nahata College of Pharmacy Mandsaur (M.P.)

S.P. Vyas, R.K. Khar ; controlled Drug DeliveryN.K.JAIN; Progress in controlled and novel drug

delivery systems.Vincent H.L. Lee and Suman k. Mukherjee ;

Encyclopedia of pharmaceutical Technology. Edi 2007Van den Mooter G. V., Kinget R, (1995) Oral colon-

specific drug delivery: a review DrugDeliv, 2: 81-93.Sarasija S, Hota A. (2002) Colon-specific drug delivery

systems. Ind J Pharm Sci. 62(1):1-8.Colon targeted drug delivery system: A Review on

primary and novel approaches.Oman Medical J,volume 25, issue 2, april2010.

B R Nahata College of Pharmacy Mandsaur (M.P.)

Colon-specific drug delivery system: IJPS,2000,62,1-8.

Oral colon targeted delivery systems for treatment of IBD: synthesis,in vitro and invivo assessment-IJPharm 358(2008)248-255.

Novel Pharmaceutical Approaches for Colon Drug Delivery: An overview- Journal of Pharmacy Research, july-sep 2008

B R Nahata College of Pharmacy Mandsaur (M.P.)

THANK YOU

B R Nahata College of Pharmacy Mandsaur (M.P.)