drug delivery to colon

CPS,JNIST,13031S0304

PRESENTED BY

B.KAVITHA

M.PHARMACY 2nd SEM PHARMACEUTICS 13031S0304


INTRODUCTION

Colon drug delivery has gained

increased importance not only for the treatment of local diseases associated with colon but also for its

potential for the delivery of proteins and therapeutic peptides


ANATOMY OF COLON

caecum ascending

COLON

TRANSVERSE

COLON

descending

COLON

COLON

Sigmoid

colon


ANATOMY AND PHYSIOLOGY

OF COLON

Create suitable environment for colonic microorganisms.

Storage reservoir of faceal matter .

Expulsion of the contents of the colon.

Absorption of potassium & Water from the lumen

MAJOR

FUNCTIONS OF COLON


DRUG ABSORPTION FROM COLON

Colon contents—More viscous with progressive absorption of water

& delays the diffusion of drug

from the lumen to mucosa

HYDROPHILIC DRUG

LIPOPHILIC DRUG


DISEASES ASSOCIATED WITH COLON

INFLAMMATORY BOWEL DISEASES

i)CROHN’ S DISEASE

ii)ULCERATIVE COLITIS

COLORECTAL CANCERS

AMOEBIASIS

DIVERTICULOSIS

DIARRHOEA


ADVANTAGES

Increases the absorption of poorly absorbable drugs due to high retention time of colon

Minimizes first pass metabolism

Decreases the side effects in associated with the treatment of colon diseases

Provides suitable environment for the absorption peptides & proteins that are sensitive to gastric fluid


LIMITATIONS

Multiple manufacturing steps.

The resident microflora could also affect colonic

performance via metabolic degradation of the drug.

Bioavailability of drug may be low due to potentially

binding of drug in a nonspecific way to dietary

residues, intestinal secretions, mucus or faecal matter.

Viscosity of luminal contents is high which hinder he

dissolution & drug release from the formulation


PHYSIOLOGICAL

FACTORS

Transit time

pH of colon

Colonic Microflora and enzymes

PHARMACEUTICAL FACTORS

Drug candidates

Drug carriers


PHYSIOLOGICAL FACTORS

TRANSIT TIME

Transit time of dosage

form is highly variable &

depends on

Subject Fed / fasted.

Food increases transit

residence

Properties of dosage

form. (Size & Density).

Fasted state 10min

-2hrs

Fed state >2 hrs

Small

intestinal transit

3-4 hrs

Colonic

transit

20-35 hrs


PH OF COLON

Stomach

Fasted state

Fed state

1.5 – 2

2 - 6

Small intestine 6.6 – 7.5

Ascending colon

Transverse colon

Descending colon

6.4

6.6

7.0

PH Varies through out the GIT which leads to earlier

disintegration and dissolution of drug


PHARMACEUTICAL FACTORS

Should be poorly

absorbed from

stomach & small

intestine

Stable at alkaline PH

of GIT

Selection of carrier

depends on nature of

drug

Physiochemical

factors like chemical

nature, stability should

be considered while

selecting the carrier

DRUG CANDIDATE DRUG CARRIER


APPROACHES FOR COLON TARGETED DRUG

DELIVERY SYSTEM

PRIMARY APPROACHES

NEW APPROACHES


PRIMARY APPROACHES FOR

CTDDS

PRIMARY APPROACHES

PH sensitive polymer Coated DDS

Delayed release DDS

Microbiologically

triggered DDS

PRODRUG APPROACH

POLYSACCHARIDE BASED

SYSTEM


1. PH SENSITIVE POLYMER COATED

SYSTEM

This system is based on solubility of

different polymers at different PH range, as

the PH varies at different parts of GIT

Polymers are insoluble at lower PH & get

solubilised as the PH increases i.e., colon

So formulation can be protected in

stomach & to some extent in Small

intestine

Colonic pH

pH sensitive

polymer +

drug core

Release of drug in

Colon


2.TIME CONTROLLED RELEASE

DRUG DELIVERY SYSTEMS

This approach is based on the principle of delaying the release of the drug until it enters into the colon.

The strategy in designing timed-released systems is to resist the acidic environment of the stomach and to undergo a lag time of predetermined span of time, after which release of drug take place.

The lag time in this case is the time required to transit from the mouth to colon


3.MICROBIOLOGICALLY TRIGGERED

DRUG DELIVERY SYSTEMS

The microflora of the colon, mainly consists of anaerobic bacteria, e.g. bacteroides, bifidobacteria, eubacteria, clostridia, enterococci etc.

This microflora fulfills its energy needs by fermenting various types of substrates that have been left undigested in the small intestine, e.g. di- and tri-saccharides, polysaccharides etc.

For this fermentation, the microflora produces a vast number of enzymes like glucouronidase, galactosidase etc which are capable of degrading the polymers in the formulation targetted for colon


i) PRODRUG APPROACH

Prodrug is inactive form of parent drug that undergoes enzymatic transformation to release the active drug

Prodrugs are prepared by linking the active drug with hydrophobic moieties like amino acids, glucose

Most widely used prodrug approaches are

Azo prodrugs

Dextran prodrugs

Cyclodextrins prodrugs

Glycoside prodrugs


PRODRUG APPROACH


ii) POLYSACCHARIDE BASED DRUG

DELIVERY SYSTEM

Natural polysaccharides are either modified or

mixed with water insoluble polymers like

guargum,chitosan,alginates

This polysaccharides are broken by colonic

microflora to simple polysaccharides


NEW APPROACHES FOR TARGETED COLON DRUG DELIVERY SYSTEMS

PRESSURE CONTROLLED DDS

OSMOTIC CONTROLLED DDS

PULSATILE DDS

AZO HYDROGELS

MULTIPARTICULATE SYSTEM BASED DDS

PULSINCAP

PORT SYSTEM

CODES


1. PRESSURE CONTROLLED DRUG

DELIVERY SYSTEM

Relies on the relatively strong peristaltic waves

that occur in the colon which leads 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.

The intestinal pressure developed varies with

circadian rhythms, state of the body


1. PRESSURE CONTROLLED DRUG

DELIVERY SYSTEM

PCDDS consists of drug in a capsule coated with water insoluble polymer like Ethyl cellulose

Drug is introduced in to the capsule along with suppository base. After administration suppository base dissolves & water is absorbed in to the capsule resulting in increased pressure in the capsule

System can be developed in such a way that withstands the pressure in intestine and ruptures in response to raised pressure in colon due to peristaltic movement


2.CODESTM

This System consists of a core tablet

coated with 3 layers of polymer coating

Outer coating : Enteric coating which

protects the tablet in stomach

Middle coating : Acid soluble coating which

protects the tablet in intestine

Inner coating : polysaccharide layer, which

gets degraded by microbes upon reaching

the colon.

ENTERIC COATING

ACID SOLUBLE COATING

POLYSACCHARIDE COATING


CODESTM


3.OSMOTICALLY CONTROLLED

DRUG DELIVERY SYSTEM The OROS-CT system can be single osmotic

unit or may incorporate as many as 5-6 push-pull units, each 4mm in diameter, encapsulated with in a hard gelatin capsule

Each bilayer push pull unit contains an osmotic push layer and a drug layer, both surrounded by a semi permeable membrane.

An orifice is drilled through the membrane next to the drug layer.


OSMOTICALLY CONTROLLED

DRUG DELIVERY SYSTEM


OSMOTICALLY CONTROLLED DRUG DELIVERY

SYSTEM

Immediately after the OROS-CT is swallowed, the gelatin capsule containing the push-pull units dissolves. Because of its drug-impermeable enteric coating, each push-pull unit is prevented from absorbing water in the acidic aqueous environment of the stomach and hence no drug is delivered.

As the unit enter the small intestine, the coating dissolve in this higher pH environment (pH >7), water enters the unit, causing the osmotic unit to swell and forces drug gel out of orifice at a controlled rate.


4.PULSATILE COLON TARGETED DRUG DELIVERY

SYSTEMS

i) PULSNICAP SYSTEM

It consists of enteric coated capsule containing

water soluble cap and water insoluble body.

The body is loaded with Hydrogel plug and drug

layer

Enteric coat dissolves in small intestine and the

water soluble cap also dissolves.

The Hydrogel plug absorbs water and swell and

release drug at a predetermined lag time of 4 hours

i) PULSINCAP SYSTEM


PULSINCAP SYSTEM


ii) PORT SYSTEM

In this system capsule body with

osmotically active agent and drug

formulation is enclosed in semi permeable

membrane

When capsule comes in contact with the

dissolution media, semi permeable

membrane permits the fluid flow in to the

capsule resulting in development of

pressure in the capsule which leads to drug

release


PORT SYSTEM


5.MULTI PARTICULATE SYSTEM BASED DRUG

DELIVERY

Multi particulate system includes

pellets,Microparticles,granules,nano

particles

Multi particular system is more preferred over single dosage forms as this system enables the drug to reach

the colon quickly and retain for a longer period of time


MULTI PARTICULATE SYSTEM

BASED DRUG DELIVERY


EVALUATION PARAMETERS

EVALUATION PARAMETERS

INVITRO EVALUATION

INVIVO EVALUATION

CLINICAL EVALUATION


INVITRO EVALUATION

Invitro evaluation includes

i)in vitro dissolution study

ii)in vitro enzymatic test

Dissolution is done using conventional

basket method in different buffers to

characterize the behavior of formulations at

different PH levels

In vitro dissolution study


INVITRO EVALUATION

Includes two tests

I) Drug system is incubated in fermenter containing suitable media for bacteria, amount of drug released at time intervals is determined

ii)Drug release study is performed in different buffer medium containing enzymes or cecal contents

The amount of drug released in a particular time is directly proportional to the rate of degradation of polymer

INVITRO ENZYMATIC TEST


IN-VIVO EVALUATION AND

CLINICAL EVALUATION

It is done in rats, dogs as they resemble

anatomical &physiological conditions and

microflora of human GIT

Absortion of drugs from colon can be

monitored by colonoscopy and intubations

INVIVO EVALUATION

CLINICAL EVALUATION


REFERENCES

1. Advances in Novel and Controlled Drug Delivery System,

KrishnaiahY.S.R, Satyanarayana S. Colon-specific drug delivery

systems. 1997; 89-110

2. Chaurasia M.K., Jain S.K. Pharmaceutical approaches to colon

targeted drug delivery system. Dr. Hari Singh Gour University, J

Pharm Pharmaceut Sci. 2003; 6(1):33-66.

3. N. K. Jain, Progress in controlled & novel drug delivery system, CBS

publishers & distributers 2010; 405-433.

4. Chien YW. Oral drug delivery and delivery systems. In: Chien YW

(Eds). Novel drug delivery systems. Marcel Dekker Inc. New York

1992, pp.139-196.

5. http://www.thepharmajournal.com/vol1Issue2/Issue_April_2012/5.

drug delivery to colon

Education

13031s0304 drug absorption

physiology of colon

dissolution of drug

13031s0304 approaches

13031s0304 diseases

hrs cps

treatment of colon diseases

system cps