this is my b pharm 7th sem project work.

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. CONTENTS
 Introduction
 Literature review
 Aim and objectives
 Plan of work
 References

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

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. ANATOMY OF COLON:
 Ascending colon
 Transverse colon
 Descending colon
 Sigmoid colon

8. •Serosa
•Muscularis externa
•Submucosa
•Mucosa
Layers:

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. 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. 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. 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

13. PH DEPENDENT POLYMERS:

14. MECHANISM OF ACTION:

15. TIME DEPENDENT:
Organ Transit time
Stomach <1(Fasting) , >3(Fed)
Small intestine 3-4
Large Intestine 20-30

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. 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. 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.

19. ENTERIC-COATED POLYSACCHARIDE MATRIX

20. COMPRESSION COATED TABLETS :

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

23. SL
NO.
AUTHOR/
YEAR
DRUG AND
EXCIPIENT
METHOD/
APPROAC
H
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 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

24. 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.

25. 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

26. 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

27.  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]

28.  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.

29. 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.

30. 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

31. 1) Chourasia M.K., Jain S.K.,Pharmaceutical approaches to colon specific drug delivery system,J
Pharm PharmaceutSci,2003; 6(1):33-66
2) Madhu E.N., Panaganti S., L. Prabakaran, and Jayveera K. N., Novel Colon Specific Drug
Delivery System: A Review, , IJPSR, 2011; 2(10): 2545-2561
3) Tapaswi R.D., Verma P., Matrix Tablets: An Approach towards Oral Extended, Release Drug
Delivery, International Journal of Pharma Research & Review, Feb 2013; 2(2):12-24
4) Kshirsagar S.J.,Bhalekar M.R,Umap R.R. In vitro in vivo comparison of two pH
Sensitive Eudragit polymers for colon specific drug delivery. J. Pharm. Sci.,
2009;1(4):61-70.
5) Shendge R.S., Fatima J., Sayyad, Kishor S., Salunkhe and Bhalke` R.D.,. Development of
specific delivery of aceclofenac by using effective binder system of ethyl cellulose. Int. J.
Pharm. Bio. Sci., 2010;1(3):1-5.
6) Patel B.P. and Avinash S. Dhake.,Multiparticulate approach: an emerging trend in colon specific
drug delivery for Chronotherapy, Journal of Applied Pharmaceutical Science, 2011, 01 (05): 59-
63
7) Gang C.F., An, Mei-Juan Zou, Jin Sun, Xiu-HuaHao, Yun-Xia He, Time- and pH-dependent
colon-specific drug delivery for orallyadministereddiclofenac sodium and 5-aminosalicylic
acid, World J Gastroenterol World, 2004, 10(12): 1769-1774

32. 8) Badmapriya D, Rajalakshmi A.N,Guar Gum Based Colon Targeted Drug Delivery System: In-
Vitro Release Investigation, 2011, RJPBCS, 2(3):899-907
9) Mei-Juan Z, Gang C., Hirokazu Okamoto, Xiu-HuaHao, Feng An, Fu-De Cui, Kazumi Danjo
,Colon-specific drug delivery systems based on cyclodextrin-prodrugs: In vivo evaluation of 5-
aminosalicylic acid from its cyclodextrin conjugates, World
JoranalGastroenterol, 2005, 11(47):7457-7460
10) Naikwade S., Kulkarni P., Jathar S R, Bajaj A N.,Development of new dissolution test and
HPLC-RP method for anti-parasitic ornidazole coated tablets, International Journal of
pharmaceutical Research,2010, 16(3): 478-481
11) Chauhan C.S., Singh P., Naruka, Rathore R.S., Badadwal V., Formulation and evaluation of
prednisolone tablets for colon targeted drug delivery system. J. Chem. Pharm. Res., 2(4):993-98.
12) Patel M.M., Santnu L. Patel, Manish N. Bhadani, Tejal J. Shah and Avani F. Amin, A
synchronous colon-specific drug delivery system for orally administered
mesalamine,ActaPharmaceuticaSciencia, 2009,51: 251- 260
13) Jose S, Dhanya K, Cinu TA, Aleykutty NA. Multi particulate system for colon targeted Delivery
of ondonsetrone. Ind. J. Pharm. Sci.,2010;72(1):58-64.
14) Purushothaman M., VijayaRatna J., Formulation optimization and release kinetics of tinidazole
matrix, compression and spray coated tablets: effect of organic acid on colon targeted drug
delivery system. JITPS.,2010;2(1):18-32.
15) Kushwaha P., SheebaFareed and Sanju Nanda. Promising Approaches to target drug delivery to
colon. Int. J. Ph. Sci., 2010:2(3):669-79.

33. 16) Thiruganesh R., Uma Devi SK, Suresh S. Preparation and characterization of pectin pellets of
Aceclofenac for colon targeted drug delivery. J. Chem. Pharm. Res. 2010;2(1):361-74.
17) Neekhra M., Shrivastav S., Sharma S., Molvi K.I., Kumar V., Development and evaluation of oral
colon targeted Ketorolac tromethamine capsule International Journal of PharmacueticalSciences
and Research. 2010;1(5):61-7.
18) Aswar P.B., Khadabadi S.S., Kuchekar B.S., Wane T.P., Matake N., Development and in-vitro
evaluation of colon-specific formulations for orally administered Diclofenac sodium. Arch Pharm
Sci and Res. 2009;1(1):48-53.
19) Chickpetty S.M., Baswaraj R., Studies on design and in-vitro evaluation of compression coated
delivery systems for colon targeting of Diclofenac sodium. International Journal of PharmaTech
Research CODEN(USA):IJPRIF. 2010;2(3):1714-22.
20) Ghuleprashant J., Karle Ganesh D., Das S.,. Formulation and In-vitro evaluation of colon targeted
drug delivery of Aceclofenac. Journal of Pharmacy Research,2010;3(5):1082-86.
21) Bhalke R.D., Raosaheb S., Shendge, Fatima J Sayyad, Kishore S Salunkhe. Development of colon
specific drug delivery of Aceclofenac by using effective binder system of ethyl cellulose.
International Journal of Pharma and Biosciences. 2010;1(3):1-5.
22) Davis S.S., Hardy J.G., Taylor M.J., Stockwell A., Whalley D.R., Willson C.G., The in vivo
evaluation of an osmotic device (Osmet) using gamma scintigraphy. J Pharm Pharmacol 1984; 36:
740-42

34. 21) Tripathy K.D., Essentials of Medical Pharmacology,6th edition,2009;517-519
22) Drug Bank Encyclopedia,Open Data Drug and Data Target Database
23) Wikipedia The Free Encycloprdia,sulfasalazine
24) Marvola M., Aitoh, Ponto P., Kanniksoki A., Nykanen S., Kokkonen P., Gastrointestinal
transit and Concomitant absorption of verapamil from a single unit sustained release tablet.
Drug DevIndPhram 1987; 13: 1539-09.
25) Sinha V.R. and Kumaria R., Polysaccharides for colon specific drug delivery. Int
J Pharm 2000; 224:19-38.
26) Jain S.K., Jain A., and Gupta Y., Perspectives of biodegradable natural polysaccharides for
site Specific drug delivery to the colon. J Pharm PharmaceutSci 2007; 10 (1):86-128.
29) Remington, the science and practice of pharmacy, 20th edition, pp- 1043-1044
30) Sapkal N.P., Kilor V.A., Bhusari K.P., and Daud A.S., Trop J Pharm Res. 2007;6(4):833-840.
31) Shirse P., Rao K.S., and Mohammed M., Formulation and Evaluation of Cyclodextrin
Inclusion Complex Tablets of Water Insoluble Drug-Glimipiride, IJRPC 2012, 2(1): 222-230
32) Pozzi F., Furlani P., GazzanigaA., Davis S. S. and Wilding I. R., The Time-Clock® system: a
new oral dosage form for fast and complete release of drug after a predetermined lag time. J.
Control. Release, 1994; 31: 99–108.
33) Lieon Lachman, Heart A. Lieberman, Joseph L. Kanig, The theory and practice of industrial
pharmacy, 3rd Edition, Varghese publishing house, Bombay, 1990, pp 298-303.