Targeted drug delivery into the colon is highly desirable for local treatment of a variety of bowel diseases such as ulcerative colitis, Crohn’s disease, amoebiasis, colonic cancer, local treatment of colonic pathologies, and systemic delivery of protein and peptide drugs, NSAIDs, steroids. The colon is believed to be a suitable absorption site for peptides and protein drugs for the following reasons; (i) less diversity, and intensity of digestive enzymes, (ii) less proteolytic activity of colon mucosa than that of small intestine. CRITERIA: Drugs used for local effects in colon against GIT diseases. Drugs poorly absorbed from upper GIT. Drugs for colon cancer. Drugs that degrade in stomach and small intestine. Drugs that undergo extensive first pass metabolism. Drugs for targeting.

1. K.UMAMAHESWARA RAO
13DM1R0085 (B.Pharm)
PHARMACEUTICS

2.  Introduction
 Anatomy of colon
 Criteria of drug selection
 Approaches of colon targeting
 EVALUATION
 INNOVATIVE DEVICES
 Conclusion
 Reference
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3.  Targeted drug delivery into the colon is highly
desirable for local treatment of a variety of bowel
diseases such as ulcerative colitis, Crohn’s disease,
amoebiasis, colonic cancer, local treatment of
colonic pathologies, and systemic delivery of
protein and peptide drugs, NSAIDs, steroids.
 The colon is believed to be a suitable absorption site
for peptides and protein drugs for the following
reasons; (i) less diversity, and intensity of digestive
enzymes, (ii) less proteolytic activity of colon
mucosa than that of small intestine.
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4. Colon targeting diseases, drugs and sites
Targetsites Disease conditions Drugand activeagents
Topical action Inflammatory Bowel
Diseases, Irritable bowel
disease and Crohn’s disease.
Chronic pancreatitis
Hydrocortisone,
Budenoside,
Prednisolone, Sulfaselazine,
Olsalazine, Mesalazine,
Balsalazide
Local action Pancreatactomy and cystic
fibrosis, Colorectal cancer
Digestive enzyme
supplements
5-Flourouracil
Systemic action To prevent gastric irritation
To prevent first pass
metabolism of orally ingested
drugs
Oral delivery of peptides
Oral delivery of vaccines
NSAIDS
Steroids
Insulin
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5. ANATOMY OF COLON
The GI tract is divided into the stomach and
the small and large intestine. The large
intestine extending from the ileocecal
junction to the anus, is divided into three
main parts. These are the colon, the rectum
and the anal canal.
For the purpose of colonic drug delivery,
there are two important physiological
factors to be considered these are pH and
GI transit time.
The mid and left colon have pH values of
approximately 6.6 and 7.0. Interspecies
variability in pH is a major concern when
developing and testing colon-specific
delivery systems
Figure 1. Anatomy of large intestine
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6. Table 2. pH in the GI tract
Location pH
Oral cavity 6.2-7.4
Oesophagus 5.0-6.0
Stomach Fasted condition: 1.5-2.0
Fed condition: 3.0-5.0
Small intestine Jejunum: 5.0-6.5
Ileum: 6.0-7.5
Large intestine Right colon: 6.4
Mid colon and left colon:
6.0-7.6
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7.  Drugs used for local effects in colon against GIT
diseases.
 Drugs poorly absorbed from upper GIT.
 Drugs for colon cancer.
 Drugs that degrade in stomach and small intestine.
 Drugs that undergo extensive first pass metabolism.
 Drugs for targeting.
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Covalent linkage of drug with carriers
pH sensitive systems
Microbial triggered systems
Timed release systems
Osmotic controlled systems
Bioadhesive systems
Pressure dependent release systems

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PRIMARYAPPROACHES NEWAPPROACHES
pH Sensitive Polymer
Coated Drug Delivery to the
Colon
Delayed Release Drug
Delivery to Colon
Microbially Triggered
Drug Delivery to Colon
Pressure Controlled
Drug-Delivery Systems
Novel Colon Targeted
Delivery System
(CODESTM)
Osmotic Controlled
Drug Delivery (ORDS-
CT)

10.  The pH in the transverse colon is 6.6 and 7.0 in the
descending colon. Use of pH dependent polymers is
based on these differences in pH levels.
 The polymers described as pH dependent in colon
specific drug delivery are insoluble at low pH levels
but become increasingly soluble as pH rises.
 These processes distribute the drug throughout the
large intestine and improve the potential of colon
targeted delivery systems.
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11. Entericpolymers OptimumpHfordissolution
Polyvinyl acetate phthalate
(PVAP)
5.0
Cellulose acetate trimelitate
(CAT)
5.5
Hydroxypropyl methyl
cellulose phthalate
(HPMCP)
>5.5
Methacrylic acid
copolymer, Type C
(Eudragit L100-55)
>6.0
Cellulose acetate phthalate
(CAP) (Aquateric)
6.0
Shellac 7.0
Table 3. pH of commonly used enteric polymers.
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12.  Time controlled release system (TCRS) such as sustained or
delayed release dosage forms are also very promising drug
release systems.
 The dosage forms may also be applicable as colon targeting
dosage forms by prolonging the lag time of about 5 to 6 h.
 Enteric coated time-release press coated (ETP) tablets, are
composed of three components, a drug containing core tablet, the
press coated swellable hydrophobic polymer layer, and an enteric
coating layer.
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12Figure 2. Design of ETP

13.  The microflora of the colon is in the range of 1011 -1012 CFU/ mL,
consisting mainly of anaerobic bacteria, e.g. bacteroides,
bifidobacteria, eubacteria, clostridia, enterococci, enterobacteria and
ruminococcus etc.
 Microflora produces a vast number of enzymes like glucoronidase,
xylosidase, arabinosidase, galactosidase, nitroreductase,
azareducatase, deaminase, and urea dehydroxylase.
 Presence of the biodegradable enzymes only in the colon, the use of
biodegradable polymers for colon-specific drug delivery.
 These polymers shield the drug from the environments of stomach
and small intestine, and are able to deliver the drug to the colon.
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14.  A Prodrug is a pharmacologically inactive derivative of a
parent molecule that require some form of transformation in
vivo to release the active drug at the target site.
 This approach involves covalent linkage between the drug and
its carrier.
 Biotransformation is carried out by a variety of enzymes,
mainly of bacterial origin, present in the colon. The enzymes
that are mainly targeted for colon drug delivery include
azoreducatase-galactosidase, β- xylosidase, nitroreductase,
glycosidase deaminase, etc.
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15.  The azo linkage exhibits a
wide range of thermal,
chemical, photochemical and
pharmaceutical properties.
 The azo compounds are
extensively metabolized by
the intestinal bacteria.
 Sulphasalazine, which was
used for the treatment of
rheumatoid arthritis. This
compound has an azo bond
between 5-ASA and
sulphapyridine.
 Include naturally occurring
polysaccharides obtained
from plant (guar gum, inulin),
animal (chitosan, chondrotin
sulphate), algal (alginates) or
microbial (dextran) origin.
 The polysaccrides can be
broken down by the colonic
microflora to simple
saccharides. Therefore, they
fall into the category of
“generally regarded as safe”
(GRAS).
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AZOREDUCTASES POLYSACCHARIDASES

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Figure 3. Linkage of drug with azo and glycoside to form prodrug

17.  Like prodrug, a number of naturally occuring polysaccharides are stable
in the upper intestine but susceptible to hydrolytic degradation in the
colon.
 Most polysaccharides can be chemically modified to optimize specific
properties, such as the ability to form impermeable films. Some of them
are:-
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POLYSACCHARIDE APPLICATIONS
Pectin & its salt form Matrices, enteric coated matrix
tablet
Chitosan & its derivative Coated capsule, microsphere
Cross linked dextran Hydrogels
Table 4. Polysaccharide based materials used to deliver drug to colon.

18.  Due to peristalsis, higher pressures are encountered in the colon
than in the small intestine.
 Takaya et al. developed pressure controlled colon-delivery
capsules prepared using ethylcellulose, which is insoluble in
water.
 In such systems, drug release occurs following the disintegration
of a water insoluble polymer capsule because of pressure in the
lumen of the colon.
 The thickness of the ethylcellulose membrane is the most
important factor for the disintegration of the formulation.
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19.  CODESTM is a combined approach of pH dependent and
microbially triggered CDDS.
 CODESTM is an unique CDDS technology that was designed to
avoid the inherent problems associated with pH or time dependent
systems
 It has been developed by utilizing a unique mechanism involving
lactulose, which acts as a trigger for site specific drug release in
the colon.
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20. Lactulose
Organic acid
Microflora
In colon
In small
intestine
In stomach Enteric coating
Acid soluble
polymer (only
slightly permeable)
Figure 4. Schematic design of CODESTM
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21.  The OROS-CT (Alza corporation) can be used to target the
drug locally to the colon for the treatment of disease or to
achieve systemic absorption.
 The OROS-CT system can be a single osmotic unit or may
incorporate as many as 5-6 push-pull units, each 4 mm in
diameter, encapsulated within a hard gelatin capsule.
 For treating ulcerative colitis, each push pull unit is designed
with a 3-4 h post gastric delay to prevent drug delivery in the
small intestine. Drug release begins when the unit reaches the
colon.
 OROS-CT units can maintain a constant release rate for up to
24 hours in the colon or can deliver drug over a period as
short as four hours.
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22. Figure 5. Osmotically controlled system (OROS-CT)22-May-17 RESN
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23.  For evaluation, not any standardized evaluation
technique is available for evaluation of CDDS
because an ideal in vitro model should posses the in-
vivo conditions of GIT such as pH, volume, stirring,
bacteria, enzymes, enzyme activity, and other
components of food.
 These conditions are influenced by the diet, physical
stress, and these factors make it difficult to design a
standard in-vitro model.
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24.  In-vitro dissolution test.
 In-vitro enzymatic test.
 In-vivo evaluation.
 Drug Delivery Index (DDI) and Clinical Evaluation of Colon-
Specific Drug Delivery Systems
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25.  The development of an oral, universally applicable, colonic drug
delivery system represents a considerable challenge to the
pharmaceutical scientist.
 Consideration must not only be given to ways in which drug
release in the colon can be achieved, but also to the behaviour and
environmental conditions experienced by the dosage form prior to
reaching the colon.
 A major problem in comparing different delivery systems is the
fact that degradation studies are performed under different
conditions.
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26.  Philip AK, Philip B. Colon Targeted Drug Delivery Systems: A
Review on Primary and Novel Approaches. Oman Medical Journal
2010; 25(2): 1-3,6-7.
 Kinget R, Kalala W, Vervoort L and Mooter GVD. Journal of Drug
Targeting 1998; 6(2): 130-131.
 Vinaykumar KV, Sivakumar T, Tamizhmani T, Sundar TR, Sarath
IC. Colon targeting drug delivery system: A review on recent
approaches. Int J Pharm Biomed Sci 2011; 2(1): 14.
 Ashford M and Fell JT. Targeting Drugs to the Colon: Delivery
Systems for Oral Administration. Journal of Drug Targeting, 1994;
2: 241,254.
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27. T H A N K Y O U
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Presentation :
k.umamaheswara rao