1. Colonic drug delivery

3. Colonic drug delivery pH Residence time Intestinal flora
Physiological variations of the GI tract: pH
High pH in colon
Residence time
High residence time in colon
Intestinal flora
High amounts of microbial flora in colon

4. Colonic drug delivery Advantages:
A colonic drug delivery system must withstand gastric and intestinal media and release drug in the colonic medium.
Advantages:
Delivery of protein and peptide drugs
Treatment of local disease of colon
Reducing the side effects of drugs
Chronopharmacotherapy
Increase the time for drug absorption
More responsiveness to absorption enhancers

5. Limitations:
Dissolution in the fluids of upper GI tract
Dependence to the physiological conditions of GI
Restricted drug absorption
Metabolic degradation of drug by colon microflora

6. Drug selection for colonic delivery
Local effect
Treatment of local diseases such as inflammatory bowel disease (IBD), Crohn’s disease, ulcerative colitis and irritatble bowel syndrome (IBS)
Examples: mesalazine, sulphasalazine, prednisolone, budesonide
Treatment of Colorectal cancer
Example: 5-fluoro uracil
Treatment of amoebiasis
Example: metronidazole

7. Drug selection for colonic delivery
Systemic effect
Peptide and protein drug delivery
Example: Insulin
Decrease in drug side effect
Example: NSAIDs
Prevent first pass metabolism of drug
Example: Hydrocortisone

8. Methods for colonic drug delivery
pH-dependent systems
Time-dependent systems
Bacterially triggered systems
Prodrugs
Polysaccharide based systems
Pressure-dependent systems
Osmotically controlled drug delivery systems
Other systems

9. pH-dependent systems gut small intestine large intestine
First part middle part terminal ileum

10. pH-dependent systems
The principal group of polymers used for this system is enteric coated polymers.
For colonic delivery, the polymers should also be able to withstand the lower pH values of the proximal part of the small intestine and to disintegrate at the neutral to slightly alkaline pH of the terminal ileum and preferably at the ileocecal junction
careful selection of enteric coat composition and thickness is needed

11. pH-dependent systems pH-dependent polymers dissolution pH
Eudragit L
Eudragit S
Eudragit FS
Polyvinyl acetate phthalate
Cellulose acetate phthalate
Cellulose acetate trimelliate
Coating of Eudragit S……………Asacol®
Coating of Eudragit L…………Salofalk® Claversal®

12. Time-dependent systems
small intestinal residence time: 3-4 h
To resist the acidic environment of the stomach and to undergo a predetermined lag time after which starts drug release
the lag time for these systems is the time requires to transit from the mouth to colon
Pentasa ® ………coating with ethyl cellulose
Pulsincap®
Time Clock®

14. Bacterially triggered systems
The slow movement of material through the colon allows a large microbial population to live there
Concentration of microorganisms in the colon is 5 orders of magnitude greater than in the stomach or small intestine (about 1011 to 1012 cfu/mL)
Predominant species of colonic bacteria include Bacteroides, Bifidobacterium, and Eubacterium
Major metabolic processes occurring in the colon are hydrolysis and reduction

15. Enzymes in colon Reducing enzymes Hydrolytic enzymes Nitroreductase
Azoreductase
N-oxide reductase
Sulphoxide reductase
Hydrogenase
Hydrolytic enzymes
Esterases
Amidases
Glycosidases
Glucuronidase
Sulfatase

16. Azo polymers Prodrugs Disadvantage: Toxicity
Balsalazide chemical structure
Disadvantage:
Toxicity

17. Prodrugs Conjugation types: Glucoronide Glycoside Dextran Cyclodextrin
Amino acid

18. Natural polysaccharides used for colonic delivery:
Advantages: - Resistant to gastric and intestinal bacteria and hydrolyze by the colonic bacteria - Non-toxic character - Inexpensive - Available
Natural polysaccharides used for colonic delivery:
Pectin
Chitosan
Guar gum
Chondroitin sulfate
Inulin
Dextran
Carageenan

19. Pressure-controlled release systems
Increase in the pressures of large intestine due to peristalsis in the colon
Ability of system to withstand the pressure in the upper GI and disruption by colonic pressure
Pressure-controlled colon delivery capsule (PCDC)

20. Osmotically controlled drug delivery systems
Based on the osmotic pressure exerted by osmogen on drug compartment with which drug get released slowly through the orifice
Rate-controlling (RC) membrane is rigid and semi-permeable and with a constant thickness, leading to a constant delivery rate.
Drug is delivered through one or more small holes which are laser-drilled or inserted through the RC membrane.

21. Other technologies
CODESTM