The document discusses colon targeting for drug delivery. It begins with the anatomy and physiology of the colon, noting its segments. It then discusses the rationale for colon targeting, including local treatment of diseases and delivery of unstable drugs. Several approaches for colon targeting are described, including pH-sensitive coatings, microbially-triggered systems, and prodrugs. Natural polysaccharides, time release systems, and osmotically controlled systems are also summarized as approaches for colon targeting. In conclusion, colon targeting provides advantages for local therapy and improved drug delivery but remains challenging.

1. COLON TARGETING
SUBMITTED TO, SUBMITTED BY,
Mr.Santosh Kumar Singh Archana Vajpayee

2. INTRODUCTION
ANATOMYAND PHYSIOLOGY OF COLON
 The colon comprises several segments:
 the cecum
 the ascending colon
 the transverse colon
 the descending colon
 the sigmoid colon
 the rectum

3. Anatomy of Colon
Mucosa
Submucosa
Muscularis
externa
Serosa

4. Rationale for the Development of Colon
Targeted Specific Drug Delivery
Targeting of drugs to colon is done for various reasons.
 Local treatment of inflammatory diseases e.g. crohn’s
disease.
 Oral delivery of peptide and protein drugs, which normally
become inactivated in upper parts of the gastrointestinal
tract.
 Oral delivery of drugs/therapeutic substances that have
undesirable side effects in the stomach and small intestine.
 Colonic diseases can be treated (e.g. colorectal cancer and
amoebiasis. ulcerative colitis, irritable bowel disease and
infections) whereby high concentration can be achieved
locally used to minimize side effects.

5. » Treatment of local pathologies
» Chronotherapy (asthma, hypertension, cardiac arrhythmias, arthritis or
inflammation )
» Greater responsiveness to the absorption enhancers.
» Less enzymatic activity
» Site for delivery of delicate drugs (Proteins and Peptides)

6. 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.
• Promising site for drug delivery
» Local disorders
» Systemic absorption
» Drugs unstable in upper GIT
» Drugs poorly absorbed from GIT
» Drugs that necessitate targeting at site

7. Advantages
» Drug directly available at the target site
» Decreased dose to be administered
» Decreased side effect
» Improved drug utilization

8. Pharmaceutical Approaches for Targeting
Drugs to Colon
» pH sensitive system
» Microbially triggered systems
» Prodrugs
Polysaccharide based systems
Time release systems
» Osmotically controlled drug delivery systems
» Pressure dependent release systems

9. pH sensitive systems
GITRACT SEGMENT PH
STOMACH 1-3
SMALL INTESTINE 5-7.5
LARGE INTESTINE 6.8-7.8
RECTUM 7.8-8

10. Mechanism of action of a pH dependent system
for targeted drug delivery to the colon
pH sensitive polymer
+
drug core
DRUG CORE
Colonic pH
Release of drug in
Colon

11. Sr. No. Polymer Threshold pH
1 Eudragit® L 100 6.0
2 Eudragit® S 100 7.0
3 Eudragit® L –30D 5.6
4 Eudragit® FS 30D 6.8
5 Eudragit® FS 30D 5.5
6 Polyvinyl acetate phthalate 5.0
7 Hydroxy propyl methyl cellulose phthalate 4.5-4.8
8 Cellulose acetate trimelliate 4.8
9 Cellulose acetate phthalate 5.0
Polymer of
methacrylic
acid are
mostly used

12. Drug Trade Name Coating Polymer / Formulation
Budesonide Entrocort®
Budenofalk®
Targit®
Eudragit® L 100-55, ethylcellulose
Eudragit® S (Dissolution pH-7)
Coated Starch Capsule
Mesalazine Claversal®
Asacolitin®
Salofalk®
Pentasa®
Mesazal®
Calitofalk®
Asacol ®
Eudragit® L100 (Dissolution pH-6)
Eudragit® S (Dissolution pH-7)
Eudragit® S (Dissolution pH-6)
Ethyl cellulose coated pellets
Eudragit® L100 (Dissolution pH-6)
Eudragit® L100 (Dissolution pH-6)
Eudragit® S (Dissolution pH-7)
Sulfasalazine Azulfidine®
Colo-Pleon®
Cellulose acetate phthalate (Dissolution pH-
6.2-6.5)
Eudragit ® L100-55 (Dissolution pH-5.5)

13. Microbially Triggered Systems
» Bacterial count in the colon is much higher around 1010-
1011 CFU/ml.
» 400 species
» Facultative anaerobic in nature.
» Predominant species: Bacteroides, Bifidobacterium and
Eubacterium.
» Major metabolic processes occurring in the colon are
hydrolysis and reduction.

14. Colonic Microflora
Human intestinal microflora distribution in
number (Log 10 scale) per gram faeces.

15. Reducing enzymes
» Nitroreductase
» Azoreductase
» N-oxide reductase
» Sulphoxide reductase
» Hydrogenase
Hydrolytic enzymes
» Esterases
» Amidases
» Glycosidases
» Glucuronidase
» Sulfatase
» Azoreductases, which reduces azo-bonds selectively
and
» Polysaccharidases which degrades the polysaccharides.
Enzymes in Colon

16. Prodrugs
Drug Carrier Molecule
Enzymatic stimuli in the biological
environment of the GIT breaks the bond
Concept
of
prodrugs

17. Bacteria in
colon
Hydrolysis of sulphasalazine (A) into 5-aminosalicylic acid (B) and
sulfapyridine (C).
(
A
)
(
B
)
(
C
)

19. Natural Polysaccharides as Polymer for
Colon Drug Delivery
» Inulin
» Guar gum
» Pectin
» Almond gum
» Locust bean gum
» Khaya gum
» Boswellia gum
» Chitosan
» Chondroitin sulphate
» Dextran
» Cyclodextrins

20. Enteric coated matrix tablet Enteric coated matrix
tablet in upper GI
Solublization of enteric
coat and swelling of
inner matrix followed
by degradation by
colonic bacteria
Degradation of swelled
matrix tablet and drug
release
Behavior of Enteric-coated Polysaccharide
Matrix
Colonic
bacteria

21. Intact compression coated
tablet
Swelling of coat in upper GI
Environment
Swelled coat Degraded by
colonic bacterial enzymes Degradation of coat and drug
release
Compression Coated Tablets
Colonic
bacteria

22. Mixed film coated tablet Intact tablet in upper GI tract
Swelled coat Degraded by
colonic bacterial enzymes Degradation of coat and drug
release
Mixed Film Coated Tablets
Colonic
bacteria

23. 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

24. Lag Phase of
5 hrs.
obeserved

25. Osmotically Controlled Drug
Delivery Systems
Depend upon the osmotic pressure exerted by
osmogen on drug compartment with which
drug get released slowly though the orifice
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

26. Platform Technologies for CTDDS
» PULSINCAP
» OROS-CT
» CODESTM
» PORT® SYSTEM
» TIME CLOCK® SYSTEM
» CHRONOTROPIC® SYSTEM
» COLAL-PRED™
» TARGIT™ TECHNOLOGY
» ENTERIONTM CAPSULE
» TICKING CAPSULE

27. PULSINCAP

28. O
R
O
S
-
C
T

29. Conclusions
» Colonic drug delivery is one of the major challenge.
» Management of local pathologies requires efforts in decreasing or eliminating side effects .
» Drug delivery to specific site i.e. colon is a potential alternative for improvement in therapy.
» Colon provides favourable factors and conditions for designing of delivery systems.
» High commercial viability. Increasing number of drug and research work in this particular
mode of drug delivery itself shows its potential for pharmaceutical market