Download Design of colon specific drug delivery systems.

“DEVELOPMENT OF AN ORAL COLON TARGETED DRUG DELIVERY SYSTEM
CONTAINING AN ANTI INFLAMMATORY DRUG”
M.Pharm Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore – 560041
By
Mr.ANKUSH BHARDWAJ
Under the Guidance of
Prof. SATEESHA .S.B
Dept. Industrial Pharmacy
Department of Industrial Pharmacy
Acharya & B.M.Reddy College of Pharmacy
Soldevanahalli,Achit Nagar (Post)
Hesarghatta main road, Bangalore – 560 107
2012– 2013
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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1
Name and address of
candidate
Mr. Ankush Bhardwaj
S/o Gian Chand
VPO Naghiar
Teh. Jhandutta
Dist. Bilaspur
Himachal Pradesh
PIN- 174030
2
Name of institution
ACHARYA & B.M. REDDY COLLEGE OF
PHARMACY.
Soldevanahalli, Hesarghatta Main Road,
Achit Nagar Post.
Bangalore-560107
3
Course of study and
subject
M. Pharm
(Industrial Pharmacy)
4
Date of admission
15-01-2013
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Title of the project
“DEVELOPMENT OF AN ORAL COLON TARGETED
DRUG DELIVERY SYSTEM CONTAINING AN ANTI
INFLAMMATORY DRUG”
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BRIEF RESUME OF INTENDED WORK
6.1
NEED FOR THE STUDY:
The prime objective of this study is to develop oral drug delivery system
containing an anti-inflammatory drug for the treatment of inflammatory bowel
diseases. Oral route is the most preferred route for drug administration, especially
for chronic therapies where repeated administration is required. In addition,
greater convenience, less pain, higher compliance, reduced risk of cross infection
and needle stick injuries are the added advantages for oral delivery when
compared to other routes of administration1.
Despite these advantages, the oral route is not amenable to the delivery of
drug for lower gastro intestinal (GI) diseases due to their release at upper GI tract,
which leads to their limited availability at the lower GI tract. To overcome this
obstacle, there has been interest in developing site specific formulations for
targeting drug to the colon. The colon is a site where both local and systemic drug
delivery can take place2.
The new strategies of colon specific drug delivery systems have been
extensively explored during last two decades. However, the design of oral drug
delivery vehicles that effectively carry drugs to the colon site is challenging as it
requires fulfilling the following criteria: i) they need to remain intact when
traveling through the upper GI tract in order to prevent the release as well as
chemical and enzymatic degradation of the incorporated drug, ii) they should be
able to release the incorporated drugs immediately upon arriving in the colonic
region. The efficiency of these formulations is estimated by the difference
between the drug released at the colon site and the initial dosage of the drug. The
smaller in this difference, the better will be the delivery system.3
Advantages of CDDS over Conventional Drug Delivery in the treatment of
Chronic colitis, namely ulcerative colitis, and Crohn’s disease are greatly
appreciated. Administration of glucocorticoids and other anti-inflammatory
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drugsnamely dexamethasone and methyl prednisolone by oral and intravenous
routes
produce
systemic
side
effects
including
adenosuppression,
immunosuppression and bone resorption. The potent NSAIDs like Naproxen,
Sulindac, Flubiprofen, Polaprezinc and Ibuprofen are also used for reducing the
inflammation in IBD. Frequent administration of these drugs by oral route may
induce gastritis and ulceration in the upper part of the GIT. Thus selective delivery
of drugs to the colon could not only lower the required dose but also reduce the
systemic side effects caused by high doses4.
Different approaches are designed based on prodrug formulation, pH-sensitivity,
time-dependency (lag time), and osmotic pressure etc., to formulate the different
dosage forms like tablets, capsules, multiparticulates, microspheres for colon
targeting5.
pH sensitive and time dependent polymers are the right candidates for
intended drug delivery system to target the drug to colon. Literature revels that
Eudragit polymers are being used for development of colon drug delivery systems.
Particularly Eudragit S100 and Eudragit FS 30D are resistant to acidic to neutral
pH conditions but sensitive to alkaline pH conditionsand therefore will not allow
the drug to solubilize in the stomach but it will deliver the drug to the colon.
Hence, these polymers can be utilized to target the drug to colon6.
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6.2
REVIEW OF LITERATURE
1. Shivkumar et al., have prepared the pH sensitive multi-particulate system of
diltiazem hydrochloride for colon targeting. The particles were prepared
using Eudragit S-100 by extrusion spheronization method. The In-vitro
dissolution study of the pellets performed following pH progression method
showed that the drug release was depended on the coat weight applied and
pH of the dissolution media7.
2. Kabra AO et al., have used 10% (w/w) solution of polymethacrylates.
Eudragit L100 and Eudragit S100 been prepared in isopropyl alcohol: water
(9:1) mixture. The ratios of Eudragit S100: Eudragit L100 were 1:4. The
resulted suspension was coated on matrix tablet using coating pan. Coated
tablets were removed from the apparatus when the coating loads reached
20% (w/w).It shows the release of drug to the colon8.
3. Varshosaz et al., developed mesalazine chitosan microspheres for colon
specific delivery. As 5-ASA is rapidly absorbed from the small intestine
and it was necessary to develop a colon-specific delivery system for it,
coated chitosan microspheres prepared by an emulsion-solvent evaporation
technique. They reported that chitosan microspheres with good bioadhesive
properties can attach to colon tissue and release slowly in zero order mode9.
4. David RF et al., reviewed colon targeted delivery system for treatment of
inflammatory bowel disease designed to increase local tissue concentration
of anti-inflammatory drugs from lower doses as compared with systemic
administration. He investigated that colon delivery system relies on
temporal control, changes in pH along the GIT, the action of local enzyme
to trigger drug10.
5. Krunal MP et al., described insoluble hard gelatin capsule body filled with
ethyl cellulose microcapsules of terbutaline sulphate and sealed with a
hydrogel plug. The entire device was enteric coated so the variability of
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gastric time can be overcome and a colon specific release can be achieved11.
6. Mayur MP et al., developed a time and pH- dependent system for colon
specific drug delivery of mesalamine. The core tablet of mesalamine was
compression coated with a pH- independent hydrophilic polymer
(Hydropropylmethyl cellulose) which was then coated with a pHDependent methacrylic acid copolymer (Eudragit S100). The coating
thickness and grades of HPMC were optimized to set a desired lag time in
the intestine. From the in-vitro evaluation it revealed that the developed
CDDS can exhibit site-specific drug targeting to the colon12.
7. Sanket DG et al., has formulated and evaluated the colon targeted tablets of
secnidazole for the treatment of amoebiasis. The colon, as a site for drug
delivery, offers distinct advantages on an account of a near neutral pH, a
much longer transit time, relatively low proteolytic enzyme activity and a
much greater responsiveness to absorption enhancers. The formulated
tablets were evaluated for hardness, friability, weight variation, drug
content, in-vitro and stability study13.
8. Chetan CS et al., prepared pH dependent tablet for colon targeting by using
copolymers of Eudragit S 100 and L 100.The results of the study
demonstrated that the pH dependent tablet system is a promising vehicle for
preventing rapid hydrolysis in gastric environment and improved oral
bioavailability of drug for the treatment of ulcerative colitis14.
9. Naikwade SR et al., were prepared matrix systems of tinidazole (500 mg)
by using swell able and pH dependent polymers and enteric coated in order
to overcome variability in gastric emptying time and delay in the release.
This study concluded that the single enteric coated tinidazole (500 mg)
tablet per day could be used in place of 3-4 doses of 500 mg tinidazole
conventional tablet with better control of drug release for targeted drug
delivery15.
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10.Mayur MP et al., have developed tablets of indomethacin using
polysaccharides and polymers like xanthan gum, guar gum, chitosan. The
developed tablets were enteric coated with Eudragit-L 100 to give
protection in the stomach. The tablets were tested in-vitro for their
suitability as colon specific drug delivery systems. The drug release studies
were carried out in simulated stomach environment (pH 1.2) for 2h
followed by small intestinal environment at pH 6.8. The formulated tablets
are able to deliver the drug to the colon successfully16.
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6.3
OBJECTIVE OF THE STUDY
 Design of colon specific drug delivery systems.
 Evaluation of various polymers for their suitability as oral colon specific
drug delivery system.
 In-vitro drug release studies in various simulated biological fluids to ensure
delivery of drug to colon.
 Assessment of stability of the formulation.
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7.0
MATERIALS AND METHODS
7.1
SOURCE OF DATA
1) Review of literature from:
a. Journals – such as

Indian Journal of Pharmaceutical Sciences.

Oman Medical Journal.

Research Journal of Pharmaceutical, Biological and Chemical
Sciences.

Journal of Microencapsulation.

Indian Journal of Pharmaceutical Sciences.

Journal of Chemical and Research.

European Journal of Pharmaceutical Sciences.

International Journal of Pharmaceutical Sciences.

Protocol for life Balance etc.
b .Reference books- such as
 Essentials of Medical Pharmacology, 6th edition- KD Tripathi.
a. World Wide Web
b. J-Gate@Helinet, etc.,
c. www. Drugbank.com
2) College library.
7.2
MATERIALS:
DRUG: Anti inflammatory agents such as polaprezinc, Noproxen, Ibuprofen etc
POLYMERS: Eudragit S100, Eudragit FS 30D Eudragit L100, etc.
EXCIPIENTS: Excipients as required etc.,
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METHODS
 Preformulation studies of drug & selected polymer
a. Formulation design using various polymers.
b. Physico-chemical characterisation of Drug and Excipients.
c. Compatibility studies between the formulation ingredients by
FTIR/DSC.
1. Evaluation of powders and granular properties.
2. Evaluation of tablets for following parameters
 Hardness, Friability, Thickness, Tensile Strength, Drug Content
Uniformity, etc.,
a) In-vitro dissolution studies using simulated gastric fluid, simulated
intestinal fluid and simulated colonic fluid.
b) Drug release characterization by fitting into various kinetic models.
c) Design of Enteric Coating Solution, Assessment and optimization of
coating process parameters.
d) Short term stability studies for the best formulation.
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7.3
DOES THE STUDY REQUIRE ANY INVESTIGATION TO BE CONDUCTED ON
PATIENT OR OTHER HUMANS OR ANIMALS?
“ NO”
7.4
HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN
CASE OF 7.3?
“NOT APPLICABLE”
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REFERENCES:-
1. Chen H, Langer R. Oral particulate delivery: Status and future trends. Adv
Drug Deliv Rev 1998;34(3):339-50.
2. Philip AK, Philip B.Colon Targeted Drug Delivery Systems: A review on
primary and novel approaches. Oman Med J 2010;25(2):1-9.
3. Gangurde HH, Chordiya MA, Tamizharasi S, Sivakumar T. Diseases,
approaches and evaluation parameterrs for colon specific drug delivery: a
review. Int J Drug Res Tech 2012;2(3):239-62.
4. Bussemer T, Otto I, Bodmeier R. Pulsatile drug-delivery systems. Crit Rev
Ther Drug 2001;18:433-58.
5. Aggarwal S, Sharma S, Lal S, Choudhary N. Recent trends in Colon
targeted drug delivery system. Res J Pharm Biol Chem Sci 2011;2(4):40615.
6. Vyas SP, Khar KR. Controlled Drug Delivery Concepts and Advances.1 st
Edition. Vallabh Prakashan: New Delhi 2002:232-3.
7. Shivkumar HN, Sarsija S, Desai BG. Design and evaluation of pH-sensitive
multi-particulate systems for chronotherapeutic delivery of diltiazem
hydrochloride. Ind J Pharm Sci 2006;68:781-7.
8. Kabra AO, Zavare SS, Wanare RS. Hydrophilic polymers in formulation of
sustained-release coated matrix tablets of 5-amino salicylic acid for
targeting colon. Int J Res Pharm Biomed Sci 2011;2(1):1-7.
9. Varshosaz J, Dehkordi AJ, Golafshan S. Colon specific delivery of
mesalazine chitosan microspheres. J Microencapsulation 2006;23(3):32939.
10.David RF. New oral delivery systems for treatment of inflammatory bowel
disease. Advan Drug Del Rev 2005;57:247-65.
11.Sinha VR, Kumria R. Microbially triggered drug delivery to the colon. Eur J
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Pharm Sci 2003;18(3):115-29.
12.Mayur MP, Santnu LP, Manish NB, Tejal JS, Avani FA. A Synchronous
colon – specific drug delivery system for orally administered mesalamine.
Acta Pharm Sci 2009;51:251-60.
13.Sanket DG, Priyanka RP, Girish KJ, Nishant NU, Upendra N. Formulation
development and evaluation of colon targeted tablets of secnidazole for the
treatment of amoebiasis. Int J Pharm Sci Rev Res 2010;5(3):64-71.
14.Chetan SC, Pushpendra SS. Naruka, Rajendrapal SR, Viral KB. Formulation
and evaluation of prednisolone tablet for colon targeted drug delivery
sytems. J Chem Pharm Res 2010;2(4):993-8.
15.Naikwade SR, Kulkarni PP, Jathar SR, Bajaj AN. Development of time and
pH dependent controlled release colon specific delivery of tinidazole. J
Pharm Sci 2008;16(3):119-27.
16.Sinha VR, Kumria R. Binders for colon specific drug delivery: an in-vitro
evaluation. Int J Pharm 2002;29:23-30.
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Signature of the candidate:
10
Remarks of the Guide:
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Name and Designation of:
11.1 Institutional Guide:
Mr. Sateesha S.B
Asst. Professor
Dept. of Industrial Pharmacy
Acharya & B.M. Reddy College of Pharmacy,
Bangalore-560 107
11.2 Signature:
11.3 Head of the Department:
Dr. Roopa Karki
Professor & HOD
Dept. of Industrial Pharmacy
Acharya & B.M. Reddy College of Pharmacy,
Bangalore-560 107
11.4 Remarks of the HOD:
11.5 Signature
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12.1 Remarks of the Principal
12.2 Signature
Dr. Goli Divakar
Principal
Acharya & B.M.Reddy College of Pharmacy,
Soldevanahalli,
Hesaraghatta main road,
Bangalore-560107
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