FORMULATION DESIGN AND DEVELOPMENT OF COLON SPECIFIC MATRIX TABLETS OF 5-

AMINO SALICYLIC ACIDProject seminar presentation

ForPartial Fulfillment of the requirements for the award of

“Degree of Bachelor of Pharmacy”By

Mainak DasB.Pharm. (7th Semester)Regd. No.: 1003254038

Under the guidance of

Dr. Prasanta Kumar Choudhury M.Pharm., Ph.D.

Assistant ProfessorRoyal College of Pharmacy & Health Sciences, Berhampur , Affiliated to Biju patnaik University of Technology, Rourkela,

Odisha2013-14

CONTENTS

Introduction

Literature review

Aim and objectives

Plan of work

References

INTRODUCTIONTargeted 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,

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)

ADVANTAGES:

Targeted drug delivery to the colon. Decrease in dose administration. Decrease side effects. Improved drug utilization.

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

ANATOMY OF COLON:

Ascending colon Transverse colon Descending colon Sigmoid colon

•Serosa

•Muscularis externa

•Submucosa

•Mucosa

Layers:

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.)

HUMAN DIGESTIVE TRACT PH RANGE

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

DISORDERS OF COLON INFLAMMATORY BOWEL

DISEASE 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.

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

PH DEPENDENT POLYMERS:

MECHANISM OF ACTION:

pH sensitive polymer

TIME DEPENDENT:

Organ Transit time

Stomach <1(Fasting) , >3(Fed)

Small intestine 3-4

Large Intestine 20-30

BACTERIA DEPENDENT:Major metabolic processes occurring in the colon are hydrolysis and reduction

Enzymes in Colon:

Reducing enzymes Hydrolytic enzymesNitroreductase EsterasesAzoreductase AmidasesN-oxide reductase GlycosidasesSulphoxide reductase GlucuronidaseHydrogenase Sulfatase

Azoreductases, which reduces azo-bonds selectively and

Polysaccharidases which degrades the polysaccharides

.

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.

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.

 

ENTERIC-COATED POLYSACCHARIDE MATRIX

COMPRESSION COATED TABLETS :

NATURAL POLYSACCHARIDES AS POLYMER FOR COLON DRUG DELIVERY

Chitoson Pectin Guar gumChondroitin sulphateDextran Almond gum Locust bean gumCyclodextrins Inulin Boswellia gumKhaya gum

LITERATURE REVIEW

SL NO.

AUTHOR/YEAR

DRUG AND EXCIPIENT

METHOD/APPROACH

CONCLUSION

1. Cheng G.et al., (2004)

Diclofenac Sodium,5 Amino Salicylic Acid,Ethyl Cellulose,Eudragit L100,Eudragit S100

Time Dependent Approach

Eudragit® L100 and S100 pH- sensitive copolymersare 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

SL NO.

AUTHOR/YEAR

DRUG AND EXCIPIENT

METHOD/APPROACH

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 gumlocust bean gumHPMC

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.

SL NO. AUTHOR/YEAR

DRUG AND EXCIPIENT

METHOD/APPROACH

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

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

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]

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.

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.

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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