Download shaik zia-ur-rahman - Rajiv Gandhi University of Health Sciences

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR M.PHARM
DISSERTATION
1.
Name of the candidate
And address.
2.
3.
4.
5
Name of Institution
Course of study and subject.
Date of admission to the Course
Title of Topic:
“Formulation Design and Invitro Evaluation of oral Colon targeted drug Delivery systems for
SHAIK ZIA-UR-RAHMAN.
S/O SHAIK SHAFIQ-UR-RAHMAN,
H.No.5-2-52, Gole khana, patal nagri,
BIDAR-585401, Karnataka-INDIA.
Karnataka College of Pharmacy, Bidar-585403.
M.PHARM (INDUSTRIAL PHARMACY).
07-07-2010
5-fluorouracil in the treatment of colon cancer”.
6.
BRIEF RESUME OF THE INTENDED WORK:
6.1.Need for the Study:1-7
Colon-specific drug delivery systems have (CDDS) attracted a great deal of interest for safe
and effective therapy for the local treatment of colonic disorders. Colonic drug delivery may be
achieved by either oral or rectal administration. Conventional oral dosage forms are ineffective in
delivering drugs to the colon due to absorption of the active ingredient in the upper part of the
gastrointestinal tract. Rectal dosage forms are not much effective due to high variability in the
distribution of drug administered by this route. Therefore, CDDS which can deliver drugs to the
lower GIT without releasing them in the upper part of GI tract can be expected to decrease the sideeffects of the drug.
Among the strategies, compression coated systems seem to be superior in preventing
premature drug release in stomach and small intestine, while beginning to release at the proximal
colon. On the other hand, the compression coated systems, usually in tablet form, is convenient to
manufacture, and no special coating solvents or coating equipments are needed for coating process.
5-fluorouracil is a pyrimidine analogue and is the drug of choice for colon cancer. Usually it
is administered parentrally because absorption after ingestion is unpredictable and incomplete.
Distribution of 5-fluorouracil to undesired sites produces severe toxic effects of the gastrointestinal.
Targeting of 5-fuorouracil to the colon for the treatment of colon cancer would not only reduce its
systemic toxicity but would also show desired action with a reduced dose.
Thus the present study was proposed to develop compression-coated tablets for delivering 5fuorouracil into the colon by using natural polysaccharide or pH dependent polymers as a carrier and
to characterize its colon site-specificity.
.
6.2 Review of Literature:
A thorough literature survey on the topic has been done and very prominent are
The references that are relevant to the current investigation have been cited appropriately
and the following abstracts of the previous reports would give an insight of the investigation that has
been undertaken:
Natural polysaccharides is now extensively used for the development of solid dosage forms
for delivery of drug to the colon. The rationale for the development of a polysaccharide based
delivery system for colon is the presence of large amounts of polysaccharidases in the human colon
as the colon is inhabited by a large variety of bacteria which secrete many enzymes e.g. β-Dglucosidase, β-D-galactosidase and amylase, etc. A large number of polysaccharides have already
been studied for their potential as colon specific drug carrier systems, such as chitosan, pectin,
chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent
efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are
discussed9 .
A novel tablet formulation using guar gum as the carrier and indomethacin as a model drug has
been investigated for colon-specific drug delivery using in vitro methods. The results illustrate the
usefulness of guar gum as a potential carrier for colon-specific drug delivery. The study also reveals
that the use of 4% w/v of rat caecal contents in PBS, obtained after 7 days of enzyme induction
provide the best conditions for in vitro evaluation of guar gum10.
pH dependent tablet for colon targeting by using copolymers of Eudragit S 100 and L 100.
The influence of core tablet composition, polymer comnbination ratios and coating level on the in
vitro release rate of drug was investigated. The results showed that less then 10% drug was released
in 0.1N Hcl within 2 hour, and about 90% of the drug was released in the pH 7.2 phosphate buffer
within 6 hour. 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 colitis11.
6.3 Objective of the study:
 To prepare fast disintegrating 5-fluorouracil core tablet by direct compression technology and
to perform various quality control tests.
 After confirming compliance with the tests. The developed 5-fluorouracil core tablets were
compression-coated with combination of polymers like guar gum, pectin, HPMC and Eudragit
RS100 and RL100 with different coat weight in various ratios.
 To perform compatibility studies by using IR and DSC spectroscopy.
 To perform Powder XRD studies for crystalline nature of the drug in tablets.
 To evaluate the prepared tablets for various physical parameters like weight variation,
friability, hardness, diameter and thickness etc.
 To study in vitro drug release in pH 1.2 (2h), pH 7.4 (3h) and continued in pH 6.8 phosphate
buffer till the completion of 24 h of dissolution study.
 To ascertain the release mechanics and kinetics of drug release from 5-fluorouracil
compression- coated tablets.
 To perform stability studies as per ICH guidelines.
7.
MATERIALS AND METHODS:
7.1.
Source of data:
 The profile of 5-fluorouracil is collected from the literatures.
 It is a laboratory-based method so in vitro release data will be collected from the in vitro
dissolution studies.
 The information about formulation and evaluation parameters will be collected by referring
to journals like Indian journal of pharmaceutical sciences, Indian drugs, AAPS
pharmascitech, Journal of research in medical sciences, Scientia Pharmaceutica, The Indian
Pharmacist, Iranian journal of pharmaceutical research etc.
 Recent information in the area will be updated by literature survey through e-publishing,
Internet and current periodicals.
 Compatibility studies between drug and polymers will be done by IR spectroscopy available
in our college laboratory.
 All the basic facilities like dissolution test apparatus USPXXIV, minipress punching
machine, hardness tester, Roche’s Friabilator etc. are required to carry out the work are
available in our college laboratory.
7.2 METHOD OF COLLECTION OF DATA:
Phase 1:
 Preformulation studies like angle of repose, bulk density & compressibility are performed for
core powder formulation and coat formulation.
 Compatibility studies between drug and polymers or excipients will be carried out by IR and
DSC spectral data.
 Drug content uniformity will be known by performing assay of the prepared formulations in
simulated fluid by UV spectrophotometer at 266nm.
Phase 2
 The developed 5-fluorouracil core tablets were compression-coated with combination of
polymers like guar gum, pectin, HPMC and Eudragit S100 and L100 with different coat
weight in various ratios and were evaluated for physico-chemical characteristics.
 In vitro drug release profile by using USP-XXIV tablet dissolution tester. Samples will be
with drawn at regular time intervals up to 24 hours and analyzed by UV-visible
spectrophotometry at 266nm to determine the amount of drug released with respect to time.
Phase 3
 Statistical analysis of data obtained from the results.
Phase 4
 Stability studies are performed for optimized formulations as per ICH guidelines.
7.3
Does the study require any investigation or intervention to be conducted on
patients or other humans or animals? (If so please describe briefly).
----------------- Not under the plan of the work------------
7.4
Has ethical clearance been obtained from your institution in case of 7.3?
--------------- Not applicable---------------
8.
LIST OF REFERENCES:
1) Samia Omar, Basmah Aldosari, Hanan Refai, Omaimah al Gohary. Colon-specific drug delivery
for mebeverine hydrochloride. Journal of drug targeting., 2007, 15 (10), pp 691-700.
2) Mayur M. Patel., Tejal, J. Shah, Avani, F. Amin. Design, Development and Optimization of a
Novel Time and pH-Dependent Colon Targeted Drug Delivery Systems. Pharmaceutical
Development and Technology., 2009, 14, 62-69.
3) Sinha V.R., Mittal, B.R.,Bhuttani, K.K.,Racing Kumaria. Colonic drug delivery of 5Fluorouracil: an in vitro evaluation. Int.Journal of Pharmaceutics., 2004, 269, 101-108,
4) Baojain, Wu. Ningyun Shun., Xiuli Wei., Wei Wu. Characterization of 5-Fluorouracil Release
from Hydroxy propyl methyl cellulose Compression-Coated Tablets. Pharmaceutical
Development and Technology. 2007, 12, 203-210.
5) Potter, J.D. Colorectal cancer: molecules and population. J.Natl. Cancer Inst., 1999, 91, 916932.
6) Calabresi, P., Chabner, B. A. Chemotherapy of neoplastic diseases. In Goodman and Gilman’s,
the pharmacological basics of Therapeutics, 9th Ed.; McGraw-Hill: New Delhi, 1996; 12251232.
7) Hahn, R.G., Moertel, C.G., Schutt, A.J. A double blind comparison of intensive course of 5fluorouracil by oral versus intravenous route in the treatment of colorectal carcinoma. Cancer.,
1975, 35, 1031-1035.
8) Diasio R.B. Harris, B.E. Clinical pharmacology of 5-floropuracil. Clin. Pharmacokinetic. 1989,
16, 215-237.
9) Sinha VR, Rachna K. Polysaccharides in colon-specific drug delivery. International
Journal of Pharmaceutics. 2001; 224: 19-38.
10)
Rama Prasad Y.V., Krishnaiah Y.S.R., Satyanarayana S. In vitro evaluation of guar gum as a
carrier for colon-specific drug delivery. Journal of Controlled Release. 1998; 51: 281-287.
11) Chetan singh chauhan, Pushpendra singh S. Naruka., Rajendrapal singh Rathod and Viral Kumar
Badadwal. Formulation and Evaluation of prednisolone tablet for colon targeted drug delivery
sytems. Journal of chemical and pharmaceutical research.2010,2(4):993-998.
9.
Signature of the candidate
(SHAIK ZIA-UR-RAHMAN)
10.
Remarks of the Guide
11.
Name and Designation of
(in block letters)
12.
11.1
Guide
11.2
Signature
Forms the basis for designing novel oral colon
targeted drug delivery systems.
SIDRAMAPPA CHICKPETTY
Assistant Professor
Department of Industrial Pharmacy,
Karnataka College of Pharmacy,
Bidar-585403.
Name and Designation
(In block letters)
12.1
Co – Guide
12.2
Signature
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-----------13.
13.1
Remarks of the Chairman and
Principal.
13.2
Signature