Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, amebiasis ,irritable bowel syndrome, Crohn’s disease, chronic pancreatitis and colon cancer.

1. NOVEL DRUG DELIVERY SYSTEM FOR
COLON
Sunidhi Ph.D (Pharmaceutics)
1
Department of Pharmaceutical Sciences,
Guru Jambheshwer University of Science & Technology
Hisar, Haryana,India,125001

2. CONTENTS
 Introduction
 Need
 Merits
 Different Approaches
 Marketed Product Based on
CDDS
 References
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3. Abstract
Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range
of local diseases such as ulcerative colitis, amebiasis ,irritable bowel syndrome, Crohn’s
disease, chronic pancreatitis and colon cancer. In addition, the colon can be a potential
site for the systemic absorption of several drugs to treat non-colonic conditions. Colon
targeting is recognized to have several therapeutic advantages, such as the oral delivery
of drugs that are destroyed by the stomach acid and/or metabolized by pancreatic
enzymes so the delivery of drugs to the systemic circulation through colonic absorption
represents a novel mode of introducing peptides and protein drug molecules and drugs
that absorb poorly from the upper gastrointestinal tract (GIT) as the colon lacks various
digestive enzyme present in the upper GIT. In order to achieve effective therapeutic
outcomes, it is imperative that the designed delivery system specifically targets the
drugs into the colon.
Keywords: Novel Drug Delivery, CDDS, GIT

4. INTRODUCTION
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 Colonic delivery refers to targeted drug delivery into lower
GI tract primarily in the large intestine (i.e. colon)
 When delivery system taken orally drug releases when
come into colon
 Delayed mechanism improve efficiency of drug by
 Concentrating drug in the area where it needed most
 Minimizes potential side effects

5. Structure (anatomy) of gastrointestinal tract

7.  Ensures direct treatment at disease site
 Low dose
 Fewer systemic side effects
 Suitable site for absorption of peptides & protein
drugs
 Both systemic & local drug delivery is possible
 Suitable for the drugs like
 Polar
 Susceptible to chemical & enzymatic degradation
in upper GI
 Highly affected by hepatic metabolism
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8. MERITES
 Beneficial in treatment of chronic colitis e.g.
ulcerative colitis & Crohn’s disease
 Selective delivery of drug to colon requires low
dose & has less side effects
 Serious diseases of colon e.g. colorectal cancer treated
effectively.
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10. Conventional Pharmaceutical
approaches
 pH-dependent drug delivery
system.
 Time-dependent drug delivery
system.
 Bacteria-dependent drug
delivery system.
Novel pharmaceutical
approaches
 Pulsincap system.
 PORT system.
 CODES technology.
 Osmotic controlled drug
delivery.
 Pressure-dependent delivery.

11. PH DEPENDENT DELIVERY
In these systems drugs are formulated into solid dosage forms such as tablets,
capsules, and pellets and coated with pH sensitive polymers. which is insoluble
in acidic pH but soluble in slightly alkaline or neutral pH. As pH increases in
the intestine, the polymer dissolves and drug release takes place.widely used
polymers are methacrylic resins (Eudragits) which is available in two forms.
Eudragit L
Water soluble
pH is 6 or above
e.g.. Eudragit L100,L-30D
Eudragit S
Water insoluble
pH is 7 or above
e.g.. Eudragit s 100
Eg.Eudragit L 100 or Eudragit S is used to coat mesalazine which is unstable
in the stomach but well absorbed from the intestine.
Some other polymers are Cellulose acetate butyrate, Methacrylic acid copolymer
(type A & type B), Hydroxypropylmethylcellulose acetate Succinate(HPMCAS)

12. TIME DEPENDENT DELIVERY:
 Very promising drug release systems.
 Enteric coated time-release press coated (ETP) tablets, are composed of three
components,
 A drug containing core tablet (rapid release function).
 The press coated swellable hydrophobic polymer layer HPC,(time release function).
 An enteric coating layer (acid resistance function).
 The tablet does not release the drug in the stomach due to the acid resistance of the
outer enteric coating layer.
 After gastric emptying, the enteric coating layer rapidly dissolves and the intestinal
fluid begins to slowly erode the press coated polymer

13. Bacterial dependent delivery system:
The microflora produces a vast number of enzymes like glucoronidase,
xylosidase, arabinosidase, galactosidase, nitroreductase, azoreducatase,
deaminase, and urea dehydroxylase.
This system includes :
a) Coating with biodegradable azo-polymer.
b) Prodrugs.
c) Hydrogels.
d) Polysaccharides as carriers

14. A. coating with biodegradable azo polymers:
The azo polymers are having high degree of hydrophilicity were
degraded by colonic bacteria. Examples: Divinyl azobenzene and
substituted diamino benzene. Drugs used are insulin and
vasopressin.
B. Prodrug :
Covalent bond is formed between drug and carrier which upon oral
administration reaches the colon without release of drug in the upper
part of the gastrointestinal tract. Cleavage of linkage between drug
and carrier takes place in the colon via reduction or hydrolysis by
enzymes produced by bacteria present in the colon.
A well known colon specific prodrug ,sulfasalazine used in ulcerative
colitis & crohn’s disease. Sulfasalazine is chemically 5-aminosalicylic
acid coupled with sulfapyridine by azobonding.

15. C. Hydrogels:
 The hydrogels contain acidic co-monomers and enzymatically
degradable azo-aromatic cross-links.
 In acidic pH gel has low degree of swelling which protects
degradation of drug from stomach enzyme.
 On entering colon, gels reach the degree of swelling which makes
crosslinks accessible to enzyme.
 Crosslinks are degraded and drug is released from disintegrating
gels.

16.  Polysaccharides are used due to their large number of derivatizable
groups, wide range of molecular weights, ease of chemical
modification, and low toxicity profile.
 In the colon, natural polysaccharides are degraded by enzymes
produced by anaerobic bacteria.
 The polysaccharides that are stable in the upper part of the GIT are
preferred for targeted delivery of drug to the colon.
Polysaccharides From:
 Plant sources e.g., pectin, amylose, guar gum;
 Microbial origin e.g., dextran, xanthan gum;
 Animal origin e.g., chitosan, chondroitin sulfate;
 Algal origin e.g., sodium alginate.
D. Polysaccharides as carriers

17. l. Pulsincap
 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.
Novel pharmaceutical approaches

18.  The formulation is developed in capsule form.
 Plug is placed in the capsule.
 Hydrogel are used to seal content.
 The plug is pushed off from the capsule and drug release.
 The polymer used HPMC, Polyvinyl acetate for hydrogel.

19.  Capsule body enclosed in semipermeable membrane.
 Capsule body consist of insoluble plug.
PORT SYSTEM

20. CODES Technology
To overcome the problems associated with pH and time dependent
CTDDS, CODES Technology is developed.
It combined the properties of polysaccharides that are:
 pH sensitive and degraded by colonic microflora.
The system consists of :
 a core tablet which is coated with acid soluble material(Eudragit E)
 subsequently overcoated with an enteric material(HPMC.)
 During passage through theGIT, the enteric coating protects the tablet
while it is present in the stomach but the enteric coating dissolves in the
small intestine where pH > 6.
Once the tablet reaches the colon, the polysaccharide present inside the
tablet core will dissolve and diffuse through the coating. The bacteria
enzymatically degrades the polysaccharide into organic acid. This lowers the
pH of the surrounding system to dissolve the acid soluble coating and
subsequently drug is released.

21. Schematic representation of the principle of CODES technology.

22. OSMOTICALLY CONTROLLED COLON TARGETED
 Consists of osmotic unit.
 Encapsulated in gelatin capsule.
 Push layer are bilayered.
 Central part- drug content .
OSMOTICALLY CONTROLLED DRUG DELIVERY SYSTEM

23. Colon targeted pressure controlled drug delivery systems are developed
in such a way that they can:
 Withstand the pressure of the upper GIT
 But release their contents in the colon due to raised pressure in the
colonic region.
 Colon has higher luminal pressure
 Ethyl cellulose capsules have been used for this purpose.
Pressure-controlled drug-delivery
system

24. Marketed Product Based
on CDDS
Products
Asacol®
Drug Moiety
5-amino salicylic acid
Budenofalk® Budenoside
Approach
pH dependent coating
(Eudragit-S coated)
pH dependent coating
(Eudragit-L coated)
PulsincapTM
COLAL-PREDTM
Mesazal
Salbutamol sulphate
Prednisolone
metasulphobenzoate
Mesalamine
Time dependent system
Polysaccharide based
system utilizing amylose
pH dependent coating
(Eudragit-L coated)

25. CONCLUSION
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 The colonic region of GIT is important site for drug
delivery & absorption.
 It offers considerable therapeutic benefits to patients in
terms of both local & systemic treatment.
 For CDDS certain primary & novel approaches were
proposed.
 Identifying appropriate approach is necessary to deliver
drug in safe, effective & less expensive manner.

26. REFERENCES
 Advances in Controlled and Novel Drug Delivery. Edited by N.K.
JAIN (page no.89-119).
 Glibert S Banker (ed.), Modern Pharmaceutics (4th edn),
Marcel Dekker, New York, 2002, 527-584.
 Abdul B, John B. Perspectives on Colonic Drug Delivery,
Business Briefing, Pharmatech, 2003, 185–190.
 Bajpai S K, Bajpai M, Dengree R. Chemically treated gelatin
capsules for colon-targeted drug delivery: a novel approach, J.
Appl. Polym.Sci., 2003, 89, 2277–2282.
 Edith mathiowitz (ed.).Encyclopedia of controlled drug delivery,
John wiley and sons, Inc. Newyork, 2003, 698-726.
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27. Thank you
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