PRESENTED BY, SUBMITTED TO,

NEETU RAJPOOT Mr. Aarun Kumar Singh

M-PHARM 2nd SEMESTER Associate Professor
Devsthali Vidyapeeth College of
Pharmacy Lalpur, Rudrapur
(U.S.Nagar)

Devsthali Vidyapeeth College of Pharmacy Lalpur, Rudrapur

Udham Singh Nagar (Uttarakhand)
INTRODUCTION
Targeted drug delivery system is the system in which the
dosage form is modified to deliver the drug at the target region
or at the disease region.
In colon targeted drug delivery system the drug is targeted to
the colon. The colon targeted drug delivery system is used for
the treatment of various diseases related to colon like
inflammatory bowel disease, crohns disease, colon cancer, etc.
Definition:-Colon drug delivery system refers to targeted
delivery of drug in to the lower parts of GI tract , mainly large
intestine.
ADVANTAGES
1. Used for the effective treatment of inflammatory bowel
diseases like ulcerative colitis, crohns disease, etc.
2. Decreases the side effects in the treatment of colon diseases.
3. Prevents gastric irritation resulting due to the administration
of NSAIDs.
4. Minimizes first pass metabolism.
5. Provides suitable environment for proteins and peptides that
are sensitive to gastric fluid and digestive enzymes.
6. Increased patient compliance.
7. Decreased frequency of administration.
8. Hence decreased cost of drugs.
9. High retention time thus increasing the bioavailability of
poorly absorbable drugs.
ANATOMY & PHYSIOLOGY OF CDDS

Longest & Most mobile

part. Diameter 6cm.
LAYERS OF COLON

External coat of large

intestine
FACTORS GOVERNING THE COLON DRUG
DELIVERY SYSTEM

1. Physiological Factors:
Gastro intestinal transit time.
pH along GIT .
Colonic Micro Flora.
GIT disease state.
2. Pharmaceutical Factors:
Drug candidate
Drug carrier
 Gastro intestinal transit time.
The arrival of oral dosage form at the colon is determined by the rate
of gastric emptying & small intestinal transit time.

Gastric emptying of dosage form is highly variable depends on.

Subject Fed / fasted.
Properties of dosage form.(Size & Density).
Food increases gastric residence, some cases with regular feeding
dosage forms residence increases 12hrs.
pH along GIT .
The pH of GIT varies between different individuals. The food intake,
diseased state, etc. influences the pH of the GIT. This change in the pH in
different parts of GIT is the basis for the development of colon targeted drug
delivery systems. Coating with different polymers is done to target the drug
to the site.
pH in different parts of Colon
Part of GIT pH
Stomach: Fasted state 1.5-2
Fed state 2-6
Small intestine 6.6- 7.5
Colon:
Ascending colon 6.4
Transverse colon 6.6
Descending colon 7.0
 Colonic Micro Flora:
The GIT contains a variety of microorganisms that produces
many enzymes need for metabolism. Growth of this microflora
is controlled by the GIT contents and peristaltic movements.
The enzymes released by different microorganisms like E. coli,
Clostridia, Lactobacilli, Eubacteria, Streptococci are
responsible for the various metabolic reactions that take place
in the GIT.
GIT disease state
IBD.
Crohns disease.
Constipation.
Diarrhea.
Gastro Enteritis.
 Colonic Micro Flora.
Microorganism Enzyme Metabolic reaction

1. E.coli, Bacteroids Nitroreductase Reduces aromatic &

heterocyclic
nitro
compounds
2. Clostridia, Lactobacilli Hydrogenase Reduces carbonyl groups
&aliphatic
double bonds
3. Clostridia, Eubacteria Glucosidase Cleavage of b-glycosidase of
alcohols
& phenols
4. Eubacteria, Clostridia, Sulfatase Cleavage of O-
sulphates &
streptococci sulfamates
 2. Pharmaceutical factors
a. Drug candidates:
Due to high retention time of colon, colon causes an increase in the
absorption of poorly absorbed agents like peptides, etc. drugs used for
treatment of inflammatory bowel diseases, etc. are suitable for colon
targeted drug delivery system.

Criteria Pharmacological class

Drugs used for local action in colon Anti- inflammatory drugs
against GIT disease
Drugs used for colon cancer Antineoplastic drugs
Drugs poorly absorbed Antihypertensive, Antianginal drugs
Drugs that undergo extensive first pass Nitroglycerin & Corticosteroids
metabolism
b. Drug carriers:
The selection of carrier for CDDS depends on the nature of the
drug, disease for which the drug is used. The various
physicochemical factors of drug that effect the carrier selection
includes chemical nature, stability, partition coefficient,
functional groups of drug molecule, etc.
Approaches for colon targeted drug delivery

1. Primary approaches for colon targeted drug delivery

a. pH sensitive polymer coated drug delivery system
b. Delayed release drug delivery system
c. Microbially triggered drug delivery
2. New approaches for colon targeted drug delivery
a. Pressure controlled drug delivery system (PCDDDS)
b. CODE
c. Osmotic controlled drug delivery system (OROS-CT)
d. Pulsatile
i. Pulsincap system
ii. Port system
f. Multiparticulate system based drug delivery
a) pH sensitive polymer coated drug delivery system
The pH dependent drug delivery system is based on the solubility of different
polymers at different pH ranges. The polymers are insoluble at lower pH
values and get solubilized as the pH increases. As the polymers are insoluble
at lower pH values the polymer can protect a formulation in stomach and to
some extent in small intestine. In this way by altering the polymers used the
release of drug from the formulation can be controlled

PH
SEN
SITI
VE
LAY
ER

DRUG COLON PH
CORE
 b) Delayed or time controlled release drug delivery system
Time controlled drug delivery system includes sustained or delayed release
systems. In this system the delayed release or colon targeted drug delivery is
attained by prolonging the lag time. The transit time varies in different parts
of gastrointestinal tract. This transit time is responsible for the delayed
release of drug. The main drawbacks of this delivery system are that the
transit time varies from one person to other and amount of food intake.
 c) Microbial triggered drug delivery system
The biodegradable enzymes present in the colon are capable of degrading
the polymers used for targeting the drug delivery to colon. Different
polymers are used for preventing the release of drug in the stomach and
small intestine. When the coated formulations reach the intestine the
biodegradable polymers gets degraded by the enzymes produced by the
microbial flora and the drug gets released in the targeted region.

Prodrug is the main approach of microbial triggered drug delivery system in

which the drug release from the formulation is triggered by the microflora
present in the gut.

Prodrug is the inactive form of an active parent drug that undergoes

enzymatic transformation to release the active drug. These prodrug
molecules get hydrolysed in the presence of the enzymes released by the
microflora.
 Limitations of the prodrug approach is that it is not a very versatile
approach as its formulation depends upon the functional group available on
the drug moiety for chemical linkage. Furthermore, prodrugs are new
chemical entities, and need a lot of evaluation before being used as carriers.
 Examples of Prodrug system for CDDS

Drug Carrier Linkage hydrolysed

5-ASA Azo conjugates Azo linkage

Dexamethasone Saccharide carriers Glycosidic linkage

Prednisolone,
hydrocortisone, Glucose,galactose Glycosidic linkage
Fludrocortisone

Salicylic acid Amino acid Amide linkage

conjugates, glycine
Different polymers used for CDDS based on Microbial drug
delivery system

Class Examples

Disaccharides Lactose, Maltose

Oligosaccharides Cyclodextrins, Lactulose,

Raffinose, Stachyose

Polysaccharides Alginates, Amylose,

Cellulose, Chitosan, Starch,
Chondroitin sulphate, pectin,
xanthan gum, etc.
d) Pulsatile colon targeted drug delivery
i) Pulsincap system
In this system the formulation is developed in a capsule form. The plug
placed in the capsule controls the release of the drug. Swellable hydrogels
are used to seal the drug contents. The capsule gets swelled when it comes
in contact with the dissolution fluid and after a lag time the plug gets pushed
off from the capsule and the drug will be released.
 ii) Port system
In this system the capsule body is enclosed in a semipermeable membrane.
The capsule body consists of an insoluble plug consisting of osmotically
active agent and drug formulation. When the capsule comes in contact with
the dissolution fluid the semi permeable membrane permits the fluid flow
into the capsule resulting in the development of pressure in the capsule body
which leads to release of drug due to expelling of the plug.
PORT SYSTEM
 e) Pressure controlled drug delivery system
The pressure controlled drug delivery system consists of a capsule in
which the drug is present. These gelatin capsules are coated with water
insoluble polymer like ethylcellulose on their inner side. The drug is
introduced into the capsule along with suppository base.
The thickness of ethyl cellulose coating determines the disintegration
capacity of the capsule. After administration the suppository base dissolves
at body temperature. The water from intestinal contents is absorbed
resulting in increased viscosity which leads to an increase in the pressure in
the capsule. The pressure in the capsule expels the drug into the colon.

f) CODES technology
In this system the pH sensitive polymers are used along with the
polysaccharides that are degraded only by specific bacteria present in the
intestine. This system consists of a core tablet coated with three layers of
polymer coatings.
 The outer coating is composed of the polymer Eudragit L. This coating
gets dissolved once the tablet passes though the pyloric and duodenum and
exposes the next coating. The next coating is composed of Eudragit E. This
layer allows the release of lactulose present in the inner core.
Osmotically controlled CDDs

Drug + Excipient
 In-vitro evaluation
No standardized evaluation technique is available for evaluation of CDDS
as an ideal in vitro model should possess in-vivo conditions of GIT. The in
vitro evaluation of colon targeted drug delivery systems includes the in-vitro
dissolution study & in-vitro enzymatic test.

1. In-vitro dissolution test

The dissolution testing is done using the conventional basket method. The
dissolution testing is done in different buffers to characterize the behaviour
of formulations at different pH levels. The different media that are used for
the dissolution testing of colon targeted drug delivery are pH 1.2 to simulate
gastric fluid, pH 6.8 to simulate small intestine, pH 7.4 to simulate large
intestine. The colon targeted drug delivery systems are tested for 2hr in
0.1N HCl, 3hr in pH 6.8 phosphate buffer and finally at pH 7.4 phosphate
buffer. Buffers of the above pH are prepared to evaluate the colon targeted
drug delivery systems.
 2. In-vitro enzymatic test
There are 2 tests for the in-vitro enzymatic test.
The carrier drug system is incubated in fermenter containing suitable
medium for bacteria. The amount of drug released at different time intervals
is determined.
Drug release study is performed in buffer medium containing enzymes
pectinase, dextranase or rat or guinea pig or rabbit cecal contents. The
amount of drug released in a particular time is directly proportional to rate
of degradation of polymer carrier.

In- vivo evaluation

The in-vivo evaluation of the CDDS is done in dogs, guinea pigs, rats &
pigs as they resemble the anatomic and physiological conditions, microflora
of human GIT. The distribution of various enzymes in GIT of rat and rabbit
is comparable to that in human.
DISADVANTAGES
TIME DEPENDENT SYSTEMS:
Substantial variation in the gastric retention times.
Transit through colon is more rapid in the normal than in patients with colon
disease.
pH DEPENDENT SYSTEMS:
pH level in the small intestine & colon vary b/w & with in the individuals.
MICROFLORA ACTIVATED SYSTEM:
Diet & disease can affect colonic microflora.
Limitations
1. Multiple manufacturing steps.
2. Incomplete release of drug.
3. Lowering of bioavailability due to binding of drugs to intestinal contents.