Colon specific drug delivery system

1. Colon – Specific Drug Delivery
System
By
Dipanjoy Ghosh
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2. Colon – Specific Drug Delivery System
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3. •Introduction
•Anatomy & Physiology of Colon
•Factors governing the colon drug delivery
•Advantages
•Pharmaceutical Approaches for Targeting Drugs to Colon
•Platform Technologies for CTDDS
•Evaluation
•Conclusion
CONTENTS
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4. YANG, LIBO, JAMES S. CHU, AND JOSEPH A. FIX. "COLON-SPECIFIC DRUG DELIVERY: NEW APPROACHES AND IN VITRO/IN
VIVO EVALUATION." INTERNATIONAL JOURNAL OF PHARMACEUTICS 235.1 (2002): 1-15.
Introduction:
 Colon as a site for drug delivery.
The site specific delivery of drugs to lower parts of the GIT is advantage
for localized treatment of several colonic diseases(IDB).
The CDDS drug release and absorption should not occur in the stomach
as well as small intestine, but only released and absorbed once the system
reaches to the colon.
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5. AIEDEH K, TAHA MO. SYNTHESIS OF CHITOSAN SUCCINATE AND CHITOSAN PHTHALATE AND THEIR EVALUATION AS SUGGESTED MATRICES IN ORALLY
ADMINISTERED COLON SPECIFIC DRUG DELIVERY SYSTEM. ARCH PHARMACOL RES 1999;332:103-7
Ensure direct treatment at the disease site.
Lower dosing and less side effects.
Beneficial in the treatment of colon diseases.
Suitable absorption site for protein and peptide drugs.
Used to prolong the drug therapy.
Why is CDDS needed?
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6. TORTORA, GERARD J., AND BRYAN H. DERRICKSON. PRINCIPLES OF ANATOMY AND PHYSIOLOGY. JOHN
WILEY & SONS, 2008.
GIT:
•Stomach
•Small intestine
•Large intestine
COLON:
Colon
 Rectum
 Anal canal
Colon consists:
• Cecum
• Ascending colon
• Transverse colon
• Descending colon
• Sigmoid colon
Anatomy & Physiology of Colon
Fig.1 Anatomy of Colon 6

7. CORNES, J. S. "NUMBER, SIZE, AND DISTRIBUTION OF PEYER'S PATCHES IN THE HUMAN SMALL INTESTINE: PART I THE
DEVELOPMENT OF PEYER'S PATCHES." GUT 6.3 (1965): 225.
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8. MARTINEZ, MARILYN N., AND GORDON L. AMIDON. "A MECHANISTIC APPROACH TO UNDERSTANDING THE FACTORS AFFECTING
DRUG ABSORPTION: A REVIEW OF FUNDAMENTALS." THE JOURNAL OF CLINICAL PHARMACOLOGY 42.6 (2002): 620-643.
Gastrointestinal transit
Small intestinal transit
Colonic transit
Gastric emptying
Stomach and intestinal pH
Colonic micro flora and enzymes
Factors governing the colon drug delivery
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9. pH of GIT:
LOCATION Ph
1.STOMACH:
Fasted
Fed
1.5-2.0
3.0-5.0
5.0-6.5
2.SMALL INTESTINE:
Jejunum
Ileum
6.0-7.5
6.4
6.7-7.3
3.LARGE INTESTINE:
Right colon
Mid colon
Left colon
6.5-7.0
6.6-7.0
6.6
7.0
MASTIHOLIMATH, V. S., ET AL. "TIME AND PH DEPENDENT COLON SPECIFIC, PULSATILE DELIVERY OF THEOPHYLLINE FOR
NOCTURNALASTHMA." INTERNATIONAL JOURNAL OF PHARMACEUTICS 328.1 (2007): 49-56.
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10. YANG, LIBO, JAMES S. CHU, AND JOSEPH A. FIX. "COLON-SPECIFIC DRUG DELIVERY: NEW APPROACHES
AND IN VITRO/IN VIVO EVALUATION." INTERNATIONAL JOURNAL OF PHARMACEUTICS 235.1 (2002): 1-15.
Advantages
Drugs are directly available at the target site.
Comparatively lesser amount of required dose.
Decreased side effects.
Improved drug utilization.
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11. CHOURASIA, M. K., AND S. K. JAIN. "PHARMACEUTICAL APPROACHES TO COLON TARGETED DRUG
DELIVERY SYSTEMS." J PHARM PHARM SCI 6.1 (2003): 33-66.
pH sensitive systems
Microbially triggered system
 Prodrugs
 Polysaccharide based systems
Timed release systems
Osmotically controlled drug delivery systems
Pressure dependent release systems
PharmaceuticalApproaches for Targeting Drugs to Colon
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12. MAKHLOF, ABDALLAH, YUICHI TOZUKA, AND HIROFUMI TAKEUCHI. "PH-SENSITIVE NANOSPHERES FOR COLON-SPECIFIC DRUG
DELIVERY IN EXPERIMENTALLY INDUCED COLITIS RAT MODEL." EUROPEAN JOURNAL OF PHARMACEUTICS AND
BIOPHARMACEUTICS 72.1 (2009): 1-8.
Solid formulations for colonic delivery that are based on
pH-dependent drug release mechanism are similar to
conventional enteric-coated formulations.
Utilize enteric polymers that have relatively higher
threshold pH for dissolution.
pH sensitive systems
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13. Mechanism of action
MAKHLOF, ABDALLAH, YUICHI TOZUKA, AND HIROFUMI TAKEUCHI. "PH-SENSITIVE NANOSPHERES FOR COLON-SPECIFIC DRUG
DELIVERY IN EXPERIMENTALLY INDUCED COLITIS RAT MODEL." EUROPEAN JOURNAL OF PHARMACEUTICS AND
BIOPHARMACEUTICS 72.1 (2009): 1-8.
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14. SINHA, V. R., AND RACHNA KUMRIA. "MICROBIALLY TRIGGERED DRUG DELIVERY TO THE
COLON." EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 18.1 (2003): 3-18.
Microbially Triggered Systems
Bacterial count in the colon is much higher
around 1011-1012 CFU/ml.
 400 species
 Fundamentally anaerobic in nature.
 Predominant species: Bacteroides,
Bifidobacterium and Eubacterium.
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15. ANDROUTSOPOULOS, VASILIS P., ET AL. "EXPRESSION PROFILE OF CYP1A1 AND CYP1B1 ENZYMES IN
COLON AND BLADDER TUMORS." PLOS ONE 8.12 (2013): E82487.
Major metabolic processes occurring in the colon are hydrolysis and
reduction
Enzymes in Colon
Reducing enzymes Hydrolytic enzymes
 Nitroreductase Esterases
 Azoreductase Amidases
 N-oxide reductase Glycosidases
 Sulphoxide reductase Glucuronidase
 Hydrogenase Sulfatase
 Azoreductases, which reduces azo-bonds selectively and
 Polysaccharidases which degrades the polysaccharides
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16. MOOTER, G., ET AL. "USE OF AZO POLYMERS FOR COLON‐SPECIFIC DRUG DELIVERY." JOURNAL OF
PHARMACEUTICAL SCIENCES 86.12 (1997): 1321-1327.
Azobond prodrugs
Hydrolysis of sulphasalazine (i) into 5-aminosalicylic acid (ii) and
sulfapyridine (iii).
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17. SETCHELL, KENNETH DR. "ABSORPTION AND METABOLISM OF SOY ISOFLAVONES—FROM FOOD TO DIETARY
SUPPLEMENTS AND ADULTS TO INFANTS." THE JOURNAL OF NUTRITION130.3 (2000): 654S-655S.
Glycoside conjugates
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18. SINHA, V. R., AND RACHNA KUMRIA. "POLYSACCHARIDES IN COLON-SPECIFIC DRUG
DELIVERY." INTERNATIONAL JOURNAL OF PHARMACEUTICS 224.1 (2001): 19-38.
Enteric-coated polysaccharide matrix
Fig.3. Steps of Enteric-coated polysaccharide matrix
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19. Compression Coated Tablets
SINHA, V. R., AND RACHNA KUMRIA. "POLYSACCHARIDES IN COLON-SPECIFIC DRUG
DELIVERY." INTERNATIONAL JOURNAL OF PHARMACEUTICS 224.1 (2001): 19-38.
Fig.4. Steps in Enteric-coated polysaccharide matrix
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20. Mixed Film Coated Tablets
SINHA, V. R., AND RACHNA KUMRIA. "POLYSACCHARIDES IN COLON-SPECIFIC DRUG
DELIVERY." INTERNATIONAL JOURNAL OF PHARMACEUTICS 224.1 (2001): 19-38.
Fig.5. Enteric-coated polysaccharide matrix
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21. 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
SINHA, V. R., AND RACHNA KUMRIA. "POLYSACCHARIDES IN COLON-SPECIFIC DRUG
DELIVERY." INTERNATIONAL JOURNAL OF PHARMACEUTICS 224.1 (2001): 19-38.
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22. EVANS, D. F., ET AL. "MEASUREMENT OF GASTROINTESTINAL PH PROFILES IN NORMAL AMBULANT
HUMAN SUBJECTS." GUT 29.8 (1988): 1035-1041.
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23. Osmotically Controlled Drug Delivery Systems
Depend up on the osmotic pressure exerted by Depend
osmogen on drug compartment with which though drug get released
slowly though the orifice
Rigid semi permeable membrane
Osmotic agent layer
Delivery port
Fluid to be pumped
BINDSCHAEDLER, C., R. GURNY, AND E. DOELKER. "OSMOTICALLY CONTROLLED DRUG DELIVERY SYSTEMS PRODUCED
FROM ORGANIC SOLUTIONS AND AQUEOUS DISPERSIONS OF CELLULOSE ACETATE." JOURNAL OF CONTROLLED
RELEASE 4.3 (1986): 203-212.
Fig.6. Osmotically Controlled Drug Delivery Systems
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24. Platform Technologies for CTDDS
•PULSINCAP
•OROS-CT
•CODESTM
•CHRONOTROPIC® SYSTEM
ANKUSH, SHARMA, KANWAR KAPIL, AND SINGH AMRITPAL. "A REVIEW ON NOVEL APPROACHES FOR COLON TARGETED DRUG
DELIVERY SYSTEM." INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL & BIOLOGICAL SCIENCES 4.2 (2014).
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25. SAEGER, H., AND VIRLEY P. PULSINCAP. "MAC226: PULSED-RELEASE DOSAGE FORM." SCHERER DDS,
LTD (2004).
PULSINCAP
Fig.7 PULSINCAP 25

26. OROS-CT
PHILIP, ANIL K., AND BETTY PHILIP. "COLON TARGETED DRUG DELIVERY SYSTEMS: A REVIEW ON
PRIMARYAND NOVEL APPROACHES." OMAN MEDICAL JOURNAL 25.2 (2010): 79.
Fig. 8. OROS-CT
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27. CODESTM
DEY, SOMDIP. "SD-EQR: A NEW TECHNIQUE TO USE QR CODESTM IN CRYPTOGRAPHY." ARXIV PREPRINT
ARXIV:1205.4829 (2012).
Fig. 9. CODESTM 27

28. CHRONOTROPIC® SYSTEM
Drug containing core
HPMC Coat
Enteric coat
SINHA, V. R., AND RACHNA KUMRIA. "POLYSACCHARIDES IN COLON-SPECIFIC DRUG
DELIVERY." INTERNATIONAL JOURNAL OF PHARMACEUTICS 224.1 (2001): 19-38.
Fig. 10 CHRONOTROPIC®
SYSTEM
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29. Evaluation
Invitro models
Invitro test for intactness of coating and carriers in simulated conditions of
stomach and intestine
step1
Drug release study in 0.1N HCL for 2 hours (mean gastric emptying)
step 2
Drug release study in phosphate buffer for 3 hours (mean small intestine
transit time)
YANG, LIBO, JAMES S. CHU, AND JOSEPH A. FIX. "COLON-SPECIFIC DRUG DELIVERY: NEW APPROACHES
AND IN VITRO/IN VIVO EVALUATION." INTERNATIONAL JOURNAL OF PHARMACEUTICS 235.1 (2002): 1-15.
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30. In vitro enzymatic degradation test
Method 1:
Drug release in buffer medium containing enzymes(e.g.pectinase,
dextranase) or rat or guinea pig or rabbit decal contents
Amount of drug release in particular time directly proportional to the rate of
degradation of polymer carrier.
Method 2:
Incubating carrier drug system in fermenter
Suitable medium containing colonic bacteria (streptococcus faecium or B.ovatus)
Amount of drug released at different time intervels determined.
YANG, LIBO, JAMES S. CHU, AND JOSEPH A. FIX. "COLON-SPECIFIC DRUG DELIVERY: NEW APPROACHES
AND IN VITRO/IN VIVO EVALUATION." INTERNATIONAL JOURNAL OF PHARMACEUTICS 235.1 (2002): 1-15.
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31. Conclusion
The colonic region of the GIT has become an increasingly important
site for drug delivery and absorption.
CDDS offers therapeutic benefits to patients in both local and systemic
treatment.
Systems utilize natural materials that are degraded by colonic bacterial
enzymes.
Colon provides favorable factors and conditions for designing of
delivery systems.
High commercial viability. Increasing number of international patents
and research work in this particular mode of drug delivery itself shows
its potential for pharmaceutical market.
YANG, LIBO, JAMES S. CHU, AND JOSEPH A. FIX. "COLON-SPECIFIC DRUG DELIVERY: NEW APPROACHES
AND IN VITRO/IN VIVO EVALUATION." INTERNATIONAL JOURNAL OF PHARMACEUTICS 235.1 (2002): 1-15.
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32. THANKYOU
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