The document discusses colon targeted drug delivery. It begins with an introduction describing the desirability of targeted colon delivery. It then discusses the anatomy of the colon, criteria for drug selection, and various approaches for colon targeting including pH sensitive polymers, delayed release systems, microbially triggered delivery, and innovative devices. It also covers evaluation methods and concludes that developing an effective oral colon delivery system remains a challenge that requires consideration of the entire gastrointestinal tract environment.

1. COLON TARGETED DRUG
DELIVERY
PRACHI JOSHI
M. S. (Pharm.)
PHARMACEUTICS 2 nd SEM

2. 
 Introduction
 Anatomy of colon
 Criteria of drug selection
 Approaches of colon targeting
 EVALUATION
 INNOVATIVE DEVICES
 Conclusion
 Reference
CONTENTs
2

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.
INTRODUCTION
3

4. Table 1. 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
4

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 5

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
6

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.
Criteria of drug selection
7

8. 
Approaches of colon targeting
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)
8

9. 
 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.
pH Sensitive Polymer CoatedDrug Delivery to the
Colon
9

10. 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.
10

11. 
 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.
DelayedRelease Drug Delivery to Colon
Figure 2. Design of ETP 11

12. 
 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.
Microbially Triggered Drug Delivery to Colon
12

13. 
 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.
PRODRUG
13

14. 
Of the multitude of bacterial enzymes that are produced in colon, 2
main classes are:-
 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).
AZOREDUCTASES POLYSACCHARIDASES
14

15. 
Mechanism of prodrug
Figure 3. Linkage of drug with azo and glycoside to form prodrug
15

16.  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:-
COATING AND MATRICES
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.
16

17. 
 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.
Pressure Controlled Drug-Delivery Systems
17

18. 
 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.
Novel Colon Targeted Delivery System
(CODESTM)
18

19. 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
19

20.  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.
Osmotic Controlled Drug Delivery (ORDS-CT)
20

21. Figure 5. Osmotically controlled system (OROS-CT)
21

22. 
 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.
22
EVALUATION

23. 
 In-vitro dissolution test.
 In-vitro enzymatic test.
 In-vivo evaluation.
 Drug Delivery Index (DDI) and Clinical Evaluation of Colon-
Specific Drug Delivery Systems
23
Different methods of evaluating colon drug delivery:-

24. 
 PulsincapTM technology: R.R. Scherer International Corporation
(Michigan)
 Orbexa® Technology: Aptalis Pharmaceutical Technologies
 DIFFUCAPS® Technology
 DIFFUTAB® Technology
 SODAS® Technology
 PRODAS® Technology
 CONTIN® Technology: Purdue Pharma
 Codas® (chronotherapeutic oral drug absorption system): Elan
Corporation, USA
24
Innovative Devices

25.  Egalet®Technology: Egalet Ltd, Denmark
 IPDAS® (Intestinal protective drug absorption system):
Elan Drug Technologies
 GEOCLOCK® Technology: SkyePharma
 Geomatrix® Technology: SkyePharma
 Pulsys TM : Middle Brook Pharmaceuticals
 Minitabs®
 ACCU-T CR Tri Layer Tablets
 Banner’s Versetrol Technology
 The CeformTM technology
 Timerx® Technology
25
CONT.

26. 
 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.
CONCLUSION
26

27. 
 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.
REFERENCE
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