Colon Specific Drug Delivery System: Basics and Approaches

1. COLON DRUG DELIVERY &
APPROACHES
SWAPNIL N. JAIN
(Assistant Professor, JES’s COP, Nandurbar)
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2. Contents
 Introduction
 Rational for the development of CDDS
 Drugs suitable for colon targeting
 Approaches for The colon targeting
 Evaluation parameters
 Conclusion
 References
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3. 3
Fig. Anatomy of GI Tract:

4. 4
The role of digestive system is to break down complex
molecules, derived from ingested food, into simple ones for
absorption into the blood or the lymph.
This process occurs in five main phases, within defined
regions of the gastrointestinal system-
• ingestion (mouth);
• fragmentation (mouth and stomach);
• digestion (stomach and small intestine);
• absorption (small and large intestine);
• elimination of waste products (large intestine).

5. Anatomy of colon
It is the lowermost part of
gastrointestinal
tract.
It is divided into four parts
 Ascending colon
 Transverse colon
 Descending colon
 Sigmoid colon
The human large intestine
is about 1.5m (5ft) in length.
Introduction
Fig 1. Anatomy of colon
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6. 6
Fig. Structure of colon wall

7. 7
Location pH
Oral cavity 6.2-7.4
Oesophagus 5.0-6.0
Stomach 1.5-2.0 (Fasted condition)
3.0-5.0 (Fed Condition)
Small
intestine
5.0-6.5 (Jejunum)
6.0-7.5 (Ileum)
Large
intestine
6.4 (Ascending colon)
6.6-6.8 (Transverse colon)
6.8-7.6 (Descending colon)
Table pH values in the GI
tract

8. 8
Table: Transit time of various parts of GIT

9. 9
Functions of colon
1)Creation of a suitable environment for the growth of
colonic microorganisms.
2) Storage reservoir of fecal contents.
3) Expulsion of the contents of the colon at a suitable
time and
4) Absorption of water and Na+
from the lumen,
concentrating the fecal content, and secretion of K+
and HCO3
-
.

10. 10
Objectives
(a) To reduce dosing frequency.
(b) To delay delivery to the colon to achieve high local
concentrations in the treatment of diseases of the
distal gut.
(c) To delay delivery to a time appropriate to treat
acute phases of disease (chronotherapy).
(d) To deliver to a region that is metabolically less
hostile, e.g., to facilitate absorption of acid and
enzymatically labile materials, especially peptides.

11. 11
Factors affecting drug absorption from the colon:
1)Physical characteristics of drug (pKa, degree of
ionization, etc.)
2)Colonic residence time as dictated by
gastrointestinal tract motility
3)Degradation by bacterial enzymes and byproducts
4)Selective and non-selective binding to mucus
5)Use of chemical absorption enhancers, enzyme
inhibitors, or bioadhesives

12. Rational for the development of colon targeted
drug delivery systems
 Drugs are available directly at the target site
 Less enzymatic activity
 Lesser amount of dose is required
 Bypass initial first pass metabolism
 Local and systemic treatment
 Proteins and peptides delivery
 Reduced gastric irritation (e.g. NSAIDS)
Limitations
 Establishment of an appropriate dissolution testing system
 Bioavailability of drug may be low
 Rate limiting step for poor soluble drugs
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13. Drugs suitable for colon targeting
1. In the treatment of Inflammatory Bowel Disease (IBD)
e.g., Sulphasalazine, Osalazine, Mesalazine
2. In the treatment of colonic cancer
e.g., 5- fluorouracil, Doxorubicin, Methotrexate
3. Proteins and peptides drug delivery
e.g., Calcitonin, Insulin, Erythropoietin
4. To treat infectious diseases like Ameobiasis
e.g., Metronidazole, Albendazole
5. To treat Rheumatoid arthritis, Nocturnal asthma, Angina,
Crohn’s disease, Ulcerative colitis, etc.
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14. 14
Strategies
1.Variable pH conditions throughout the GIT
2.Colonic microflora produce a variety of enzymes
that are not present in the stomach or the small
intestine
3.The relatively constant transit time in the small
intestine of approximately 3–4 h
4.Another strategy relies on the strong peristaltic
waves in the colon that lead to a temporarily
increased luminal pressure.

15. Approaches For The Colon targeting
1.Primary approaches for colon targeting
I. pH sensitive polymer coating
II. Time controlled system
III. Microbially triggered drug delivery
 Polysaccharide based approach
 Prodrug approach
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16. 2. Novel approaches for colon targeting
I. Pressure controlled drug delivery system
II. Osmotic controlled drug delivery to colon
III. Pulsincap system
IV. Port system
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17. l. pH sensitive polymer coating
Region pH
Ascending colon 6.4
Transverse colon 6.6
Descending colon 7.0
at colon pH
pH sensitive polymer
Drug core
Drug release
Important parameters
- Selection of the appropriate polymers
- Solubility at different pH environments
Primary approaches for colon targeting
17Fig 2. Drug release

18. Table. Polymers
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19. ll. Time controlled system
In these systems the release of the drug is decided by the transit time.
This system is useful for synchronous delivery of a drug either at preselected time
or at a preselected site.
Fig3. Time controlled system
The formulation is comprised of 3
parts:-
1) a central core containing drug
and swelling excipients.
2) an inner semi-permeable
polymer membrane.
3) an outer enteric-coating which
dissolves at or above pH 5.5
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20. lll. Microbially triggered drug delivery
The colonic bacteria are predominately anaerobic in nature and secrete
enzymes that are capable of metabolizing substrates that escape the
digestion in the upper GI tract.
On reaching the colon, their is degradation of the polymer backbone by
enzyme resulting in drug release.
Table: Enzymes in colon
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21. The hydrogels contain acidic co-monomers and enzymatically degradable
azo-aromatic cross-links.
In the acidic pH of stomach, the gels have a low degree of swelling.
In colon, the gels reach a degree of swelling making the cross-links
accessible to enzymes.
Azo hydrogels
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22. Polysaccharide based approach
The polysaccharides are assessed to remain intact in physiological
environment of stomach and small intestine.
As they reach colon they are acted upon bacterial polysaccharidases
and results in degradation of the matrices.
e.g., Amylose, Pectin, Chitosan, Dextran, Guar gum, etc.
These are broken down by the colonic microflora to simple saccharides,
so these fall into the category of “generally regarded as safe” (GRAS).
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23. Prodrug approach
A prodrug is a pharmacologically inactive derivative of a parent molecule
that requires some form of transformation in vivo to release the active drug
at the target site.
Generally, a prodrug is successful as a colon drug carrier if it is
hydrophilic and bulky to minimize absorption from the upper GIT, and is
converted into more lipophilic in colon for absorption.
Limitation- It is not a very versatile approach as its formulation depends
upon the functional group available on the drug moiety for chemical
linkage.
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24. l. Pressure controlled drug delivery system
 As a result of peristalsis, higher pressures are encountered in the
colon, and which forms the basis for this system.
 Drug release occurs due to the disintegration of a water-insoluble
polymer capsule because of pressure in the lumen of the colon.
 The thickness of the polymer membrane is the critical factor for the
disintegration of the formulation.
Novel approaches for colon targeting
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25. ll. Osmotic controlled drug delivery to colon
It can be single osmotic unit or may incorporate as many as 5-6 units, each
4mm in diameter.
It can maintain a constant release rate for up to 24 h in the colon.
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Fig 4. OROS- CT

26. lll. Pulsincap system
It consists of non disintegrating half capsule body filled with drug content
sealed at the opened end with the hydrogel plug, which is covered by water
soluble cap.
Polymers used for hydrogel plug are HPMC, PVA etc.
Fig. Pulsincap system
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27. 27Fig. Mechanism of drug release

28. lV. Port system
28Fig. Drug release

29. Evaluation
1. In vitro
a) Dissolution testing
b) Enzymatic degradation testing
2. In vivo
a) Drug delivery index
= Relative colonic tissue exposure to drug
Relative amount of drug in blood
b) Animal studies
c) γ-Scintigraphy – to investigate GI performance of a formulation
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30. Marketed Formulations
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Drug Trade
name
Company
name
Therapeutic use
Mesalamine Mesacol Sun Pharma Ulcerative colitis
Osalazine Dipentum UCB Pharma Ulcerative colitis
Sulphasalazine Sazo Wallace Ulcerative colitis
Balsalazide Intazide Intas Ulcerative colitis
Diphenoxylate
HCl+ Atropine
sulphate
Lomotil RPG Life Mild ulcerative colitis
Mebeverine Colospa Solvay Irritable bowelsyndrome
Hydrocortisone
acetate
Entofoam Cipla Ulcerative colitis

31. Conclusion
This system is of prime importance in the treatment of diseases and
disorders related to colonic region.
This drug delivery requires establishment of appropriate evaluation
parameters.
The discontinuity in physiological parameters along the GI tract governs
few mechanisms to be incorporated to produce colon specific drug release.
There is a need to identify appropriate approach, which will be safe,
effective, less expensive with minimum fluctuation in drug release.
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32. References
1) Chourasia M. K., Jain S. K., (2003), Pharmaceutical Approaches to Colon Targeted
Drug Delivery System, In: Journal of Pharmaceutical Sciences, 33-66.
2) Krishnaiah Y. S. R., Styanarayana S., (2000), Colon specific drug delivery systems.
In: Jain N. K., ed. Advances in Controlled and Novel Drug Delivery. New Delhi, India:
CBS Publishers and Distributors, 89-119.
3) Kothawade P. D., Gangurde H. H., Surawase R.K., Wagh M.A., Tamizharasi S.,
Conventional and Novel Approaches for Colon Specific Drug Delivery: A Review. In : e-
Journal of Science and Technology, 33-56.
4) Patel A., Bhatt N., (2011), Colon Targeted Drug Delivery System: A Review System,
In: Journal of Pharmaceutical Sciences and Bioscientific Research, 37- 49.
5) Singh B.N., Kim K.H., In: Swarbrick J, Boylan JC., ed. (2002), Encyclopedia of
Pharmaceutical Technology, New York, Marcel Dekker, Inc, 886-909.
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33. 6) Kumar K. V., Sivakumar T., Mani T., (2011), Colon Targeting Drug Delivery System:
A review on recent approaches, In: International Journal of Biomedical Sciences, 11-
19.
7) Mehta T. J., Patel A.D., (2011), Need of Colon Specific Drug Delivery System:
Review on Primary and Novel Approaches, In: International Journal of Pharmaceutical
Research and Development, 134-153.
8) Patel N., Patel J., (2008), Novel Pharmaceutical Approaches For Colon-Specific
Drug Delivery: An Overview. In: Journal of Pharmacy Research, 2-10.
9) Prasanth V.V., Jayaprakash. R., Colon Specific Drug Delivery Systems: A Review
on Various Pharmaceutical Approaches. In: Journal of Applied Pharmaceutical
Science, 163-169.
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34. THANK YOU
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