colon specific drug delivery system


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colon specific drug delivery system

  1. 1. Project seminar presentation For Partial Fulfillment of the requirements for the award of “Degree of Bachelor of Pharmacy” By Mainak Das B.Pharm. (7th Semester) Regd. No.: 1003254038 Under the guidance of Dr. Prasanta Kumar Choudhury M.Pharm., Ph.D. Assistant Professor Royal College of Pharmacy & Health Sciences, Berhampur , Affiliated to Biju patnaik University of Technology, Rourkela, Odisha 2013-14
  2. 2. CONTENTS  Introduction  Literature review  Aim and objectives  Plan of work  References
  3. 3. INTRODUCTION Targeted drug delivery systems:  The major goal of any drug delivery system is to supply a therapeutic amount of drug to a target site in a body.  Targeted drug delivery implies selective and effective localization of drug into the target at therapeutic concentrations with limited access to non target sites.  A targeted drug delivery system is preferred in drugs having instability, low solubility and short half life,
  4. 4. WHY COLON TARGETED DRUG DELIVERY IS NEEDED?  Rational for the Development of Oral Colon Targeted Drug Delivery: • Treatment of local pathologies • Greater responsiveness to the absorption enhancers • Site for delivery delicate drugs (Proteins and Peptides)
  5. 5. ADVANTAGES:  Targeted drug delivery to the colon.  Decrease in dose administration.  Decrease side effects.  Improved drug utilization.
  6. 6. DISADVANTAGES:  There are variations among individuals with respect to the pH level in the small intestine and colon which may allow drug release at undesired site.  The pH level in the small intestine and caecum are similar which reduces site specificity of formulation.  Diet and diseases can affect drug targeting to colon
  7. 7. ANATOMY OF COLON:  Ascending colon  Transverse colon  Descending colon  Sigmoid colon
  8. 8. •Serosa •Muscularis externa •Submucosa •Mucosa Layers:
  9. 9. COLON ABSORPTION : Factors affecting colon absorption :  pH level  Colonic residence time.  Degradation by bacterial enzymes.  Local physiological actions of drug.  Disease state.  Use of chemical absorption enhancers. (eg:ethylacetoacetate.)
  10. 10. 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
  11. 11. DISORDERS OF COLON Crohn’s disease: •Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract •It is characterized by a granulomatous inflammation affecting any part of the tract, normally form fistulae. Ulcerative colitis:- •It is a chronic inflammatory disorder of colon limited to the large intestine as against the case with Crohn's Disease where any part of the alimentary tract may be involved.
  12. 12. The various pharmaceutical approaches which have been used for targeting drugs to the colon are mainly based on:  pH dependent  Time-dependent  Bacteria-dependent  Pressure dependent delivery system DIFFERENT APPROACHES
  15. 15. TIME DEPENDENT: Organ Transit time Stomach <1(Fasting) , >3(Fed) Small intestine 3-4 Large Intestine 20-30
  16. 16. BACTERIA DEPENDENT: 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 .
  17. 17. AZO BOND CONJUGATES:  SAS on colon in presence of diazoreductase cleaves the azo bond to form 5 ASA and Sulfapyridine. Hydrolysis of sulphasalazine: (i) 5-aminosalicylic acid . (ii) And sulfapyridine.
  18. 18. MATRIX TABLETS:  Introduction of matrix tablet excludes complex production procedures such as coating and pelletization  Drug release rate from the dosage form is controlled mainly by the type and proportion of polymer used in the preparations  Advantages offered by matrix tablets:  Reduction in toxicity by slowing drug absorption.  Minimize the local and systemic side effects.  Improved patient compliance.
  21. 21. NATURAL POLYSACCHARIDES AS POLYMER FOR COLON DRUG DELIVERY  Chitoson  Pectin  Guar gum  Chondroitin sulphate  Dextran  Almond gum  Locust bean gum  Cyclodextrins  Inulin  Boswellia gum  Khaya gum
  22. 22. SL NO. AUTHOR/ YEAR DRUG AND EXCIPIENT METHOD/ APPROAC H CONCLUSION 1. Cheng al., (2004) Diclofenac Sodium,5 Amino Salicylic Acid, Ethyl Cellulose,Eudragit L100,Eudragit S100 Time Dependent Approach Eudragit® L100 and S100 pH- sensitive copolymers are able to achieve site-specific drug delivery targeting at colon following oral administration 2. Patil M.M. et al., (2009) Mesalamine, Eudragit L100,Eudragit S100 Compression Coating, PH Dependent Approach Compression coating layer was adopted to delay the drug release for about 2-3 hours and to allow the tablet to pass intact through the small intestine to the colon. 3. Aswar P.B. et al., (2009) Diclofenac sodium, Guar Gum,Ethyl Cellulose Matrix tablets preparation Matrix tablets containing guar gum as a carrier and ethyl cellulose as a binder was found to be suitable for targeting Diclofenac sodium for local action in the colon
  23. 23. SL NO. AUTHOR/ YEAR DRUG AND EXCIPIENT METHOD/ APPROAC H CONCLUSION 4. Shendge R.S. et al., (2010) Aceclofenac, Ethyl Cellulose,sodium CMC,Sucrose Wet Granulation Technique The matrix tablet containing binder system of ethyl cellulose and dextrin as a carrier was found to be suitable for targeting the colon 5 Neekhra M. et al., (2010) Ketorolac tromethamine ,Guar Gum,CAP Capsule Formation That cellulose acetate phthalate coated capsules with 50% guar gum may be useful for drug targeted to the colon successfully. 6. Chickpetty S.M. et al., (2010) Diclofenac Sodium guar gum locust bean gum HPMC Compression Coated Tablets Ratio 6:4 released only 2.24% of drug in physiological environment of stomach and small intestine and released more than 90% of drug in colon.
  24. 24. SL NO. AUTHOR/ YEAR DRUG AND EXCIPIENT METHOD/APPR OACH CONCLUSION 7. Naikwade S. et al., (2010) Ornidazole, HPMC,Eudragit Matrix Tablets Preparation The formulation was found to be working as colon targeted drug delivery system. 8. Badmapriya D. et al., (2011) Guar Gum, Matrix Tablets Preparation Guar Gum colon targeting coated with two different polymeric layers resulted in the drug release in range of 57.8 to 68.38%, due to the microbial enzymatic activity
  25. 25. 3.0 DRUG PROFILE (Sulfasalazine) Sulfasalazine was developed in the 1950s specifically to treat rheumatoid arthritis.  Sulfasalazine is a sulfa drug, (a derivative of mesalazine)  It is formed by combining sulfapyridine and salicylate with an azo bond. It may be abbreviated SSZ. Structure: Chemical name: (2-hydroxy-5-[(E)-2-{4-[(pyridin-2-yl) sulfamoyl] phenyl} diazen-1-yl] benzoic acid
  26. 26.  Molecular formula: C18H14N4O5S  Molecular weight: 398.394 g/mol  Volume of distribution: 7.5 1.6 L  Half life: 5-10 hours  Clearance: 1 L/h [IV administration]
  27. 27.  Mechanism of action:  5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation.  It may be related to the anti-inflammatory and/or immuno modulatory.  Clinical studies utilizing rectal administration of Sulfasalazine, SP and 5-ASA have indicated that the major therapeutic action may reside in the 5-ASA moiety.  Route of elimination:  The majority of 5-ASA stays within the colonic lumen and is excreted as 5-ASA and acetyl-5-ASA with the feces.
  28. 28. AIM AND OBJECTIVES  Present aim of the research work is based on Formulation Design and Development of Colon Specific Matrix Tablets of 5-Amino Salicylic Acid. Here the work is emphasized on formulation of matrix tablets intended for colonic delivery.  The results are to be compared with marketed formulation to see that whether any deviation occurred between the marketed formulation and the prepared formulation.
  29. 29. PLAN OF WORK: Experimental protocol:  Selection of model drug and analytical studies.  Characterization of the drug:  Physical properties  Solubility study  UV spectral analysis  FTIR analysis  Preparation calibration curve of model drug  Preformulation Drug-Excipients compatibility study  Formulation of matrix tablets for colonic delivery.  Selection of final formulation and evaluation for potentiality to deliver the drug to colonic region.  Comparison of the drug release data and fitting to different kinetic models.  Stability studies of the optimized formulations
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