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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
1.
Name of the Candidate
and Address
SOORAJ NARAYAN
a. Permanent Address
S/O E.V Narayanan
Elavumkudy[H]
Valayanchirangara p.o
Ernakulam (D)
Pin 683556
b. Postal Address
Shree Devi College of Pharmacy
Airport Road , Kenjar Village
Malavoor Panchayat,
Manglore – 574 142.
Karnataka.
2.
Name of the Institute
3.
Course of Study and Subject
4.
Date of Admission to Course
5.
Title of the Topic:
Shree Devi College of Pharmacy
Airport Road, Kenjar village
Malavoor Panchayat,
Manglore – 574 142
Karnataka.
Master of Pharmacy in Pharmaceutics
June 2010
“FORMULATION OF SOLID DISPERSION OF KETOPROFEN &
COMPARISON OF ULCER INDEX OF KETOPROFEN SOLID DISPERSION
WITH KETOPROFEN”
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6. BRIEF RESUME OF THE INTENDED WORK:
6.1.
Need of study:
The occurrence of gastrointestinal damage (bleeding, ulceration) is probably among the
most prevalent and serious of the side-effects associated with the use of non-steroid antiinflammatory (NSAI) drugs. Ketoprofen is a potent anti-inflammatory drug. Chemically,
it is propionic acid derivative provided as a recemic mixture. This non-steroidal and nonnarcotic drug is administered systemically (via oral and parenteral route) for the control
of mild to moderate pain as well as of some postoperative and cancer pain . It has similar
pharmacological actions to other drugs in this class such as ibuprofen, fenoprofen and
naproxen. It inhibits the synthesis of prostaglandin (PG) by inhibiting the enzyme
cyclooxygenase (COX). Administration of this non-selective COX inhibitor by oral
route causes many gastrointestinal side effects, like nausea, vomiting, gastric irritation,
peptic ulceration and bleeding that limit its clinical use . Prostaglandins are ubiquitous
compounds that mediate a variety of physiologic and pathologic processes. Under
normal physiologic conditions, Prostaglandins play an essential homeostatic role in
cytoprotection of gastric mucosa, hemostasis, renal function, gestation and parturition . It
is a well accepted fact that gastrointestinal lesions produced by NSAIDs are due to two
different mechanisms: (a) direct contact with gastric mucosa through oral dose and (b)
systemic effect which may be manifested by after intravenous dosing.
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The term solid dispersion refers to a group of solid products consisting of at least two
different components, generally a hydrophilic matrix and a hydrophobic drug. The matrix
can be either crystalline or amorphous. There are many types of solid dispersions which
includes Simple eutectic mixtures, Solid solutions, Glass solutions, Amorphous
precipitation in a crystalline carrier and According to the way in which the solvate
molecules are distributed in the solvendum. when the solid dispersion is exposed to
aqueous media, the carrier dissolves and the drug releases as fine colloidal particles. The
resulting enhanced surface area produces higher dissolution rate and bioavailability of
poorly water-soluble drugs. In addition, in solid dispersions, a portion of drug dissolves
immediately to saturate the gastrointestinal tract fluid, and excess drug precipitates as
fine colloidal particles or oily globules of submicron size.Solid dispersions prevent the
direct contact of drug with gastric mucosa hence the risk of developing ulcer with
ketoprofen can be minimized by formulating as a solid dispersion.
Different methods are also been used for preparation of solid dispersions such as
Melting method, Solvent method, Melting solvent method (melt evaporation), Melt
extrusion method, Lyophilisation Technique, Melt Agglomeration Process, The Use Of
Surfactant,Micro emulsion, Electrospinning and Super Critical Fluid (Scf) Technology.
The main aim of this study to compare the ulcer index of solid dispersion of
ketoprofen with ketoprofen & to investigate wether the solid dispersion minimize the risk
of developing ulcer.
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6.2
Review of literature :
1. Amal H.E Kamal,Magda S.Sokar et al16 .Prepared the ketoprofen loaded
microcaparticles & it was found to be less ulcerogenic and they protected the
stomach by preventing the intimate contact of ketoprofen with gasric mucosa.
2. Sahu Jagadish k,Banarjee Lopamudra et al15 .Evaluated the ulcerogenicity of
ketoprofen glucopyranoside derivatives.in vivo biological screening in mice &
rats indicates that glucopyranoside derivatives of ketoprofen shows reduced
ulcerogenicity.
3. K.P.R Chowdary,K.V.V Suresh et al17.Had studied dissolution,bioavailability &
ulcerogenicity
of indomethacin solid dispersion in water soluble cellulose
polymer.The solid dispersion of indomethacin in water soluble cellulose polymer
shows better bioavailabilty&dissolution rate with minimum ulcerogenicity.
4.
Appa Rao B,B.M Shivalingam et al14 .Formulated & evaluated aceclofenac solid
dispersion for dissolution rate enhancement.Solid dispersion of aceclofenac were
prepared by using lactose,urea & mannitol to increase its aqueous solubility.
5. Singh C,Jain K.A,Agarwal et al13.Performed development,characterization &
solubility study of solid dispersion of terbinafine hydrochloride.Terbinafine HCL
when prepared as solid dispersion showed improved solubility & dissolution.The
main purpose of this investigation was to increase the solubility & dissolution rate
of terbinafine HCL by the preparation of its solid dispersion with PEG 6000 using
fusion method.
6. Ambade K.W,Jadavu S.L et al12.Prepared & evaluated
flubiprofen micro
emulsion. The purpose of the present study was to investigate the microemulsion
formulations for topical delivery of Flurbiprofen (FP) in order to by pass its
gastrointestinal adverse effects. The pseudoternary phase diagrams were
developed and various microemulsion formulations were prepared using
Isopropyl Myristate (IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant
and Sorbitan Monooleate as cosurfactant..
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6.3
Objective of the present study
The objective of the proposed study to investigate wether the solid dispersion of
ketoprofen minimize the risk of developing ulcers.
Specific objective
1. Formulation & evaluation of solid dispersion of ketoprofen
2. To compare the ulcer index of ketoprofen solid dispersion with ketoprofen.
7.
7.1
PLAN OF WORK :

Procurement of drug and raw materials.

Formulation of solid dispersion

Evaluation of solid dispersion

Procurement of the experimental animals

Comparison of ulcer index of solid dispersion of ketoprofen with ketoprofen
SOURCE OF DATA :
1) Review of literature from:
a. Journals – such as

Indian Journal of Pharmaceutical Sciences

International Journal of Pharmaceutical Sciences & Drug
Research.

Asian Journal of Pharmaceutics

International Journal of Research in Ayurveda & pharmacy

Indian Drugs
b. World Wide Web
c. J-Gate@Helinet
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7.2
MATERIALS, METHODS AND EQUIPMENTS :
MATERIALS:

Drug : Ketoprofen

Chemicals : PEG 6000,PEG 400,PEG 600,Isopropyl myristate,Tween 60,Tween
80,Propeylene glycol,Glycerol.
EQUIPMENTS

Stirrer

Dissolution apparatus

Compound microscope

U.V spectrophotometer

Analytical balance

Glass beaker
METHODS:

Formulation of solid dispersion of ketoprofen using fusion method & micro
emulsion method

Evaluation of solid dispersion

Determination of ulcer index of ketoprofen solid dispersion & ketoprofen
DETERMINATION OF ULCER INDEX
Albino rats of either sex (150-200 g) were selected for study.They were divided in
to 2 groups.
1. Control group
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2. Test group
Both groups were fasted for 12 hrs.control group were administered with
ketoprofen & test group were administered with solid dispersion of ketoprofen
twice a day for 2 days.Then the rats were sacrified day after giving the final
dose.To determine the mucosal damage,rats stomach were removed,open
along the length of greater curvature and cleaned of the derbis,washed and
examined under a microscope and ulcer were scored as
0
normal coloured stomach
0.5
red coloured stomach
1
spot ulcers
1.5
hemmorrhagic streaks
2
ulcers between 3 mm-5mm
2.5
ulcers >5
The mean ulcer score for each animal is expressed as mean ulcer index.Then
the ulcer index ofcontrol group is compare with the ulcer index of test group.
CONCLUSION :

From the above cited parameters solid dispersion of ketoprofen will be
formulated,evaluated & ulcer index of solid dispersion will be compared with
ketoprofen.
7.3
DOSE THE STUDY REQUIRES ANY INVESTIGATION OR INVESTIGATIONS
TO
BE CONDUCTED ON PATIENT OR OTHER HUMANS OR ANIMALS?IF
SO PLEASE DESCRIBE BRIEFLY:
“YES”
In-vivo animal studies using Albino rats.
7.4
HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION
IN CASE OF 7.3?
“YES”
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8.
LIST OF REFERENCE :
1.
Laurence L. Brunton,John S. Lazo,Kieth L. Parker.Goodman & Gilmans The
Pharmacological Basis of Therapeutics.2010;11thedition:678-79
2. K.D Tripathi.Essentials of Medical Pharmacology.2003;5thedition:169-71
3. David E. Golan,Ehrin J. Armstrong.Principles of Pharmacology :The
Pathophysiologic Basis of Drug Therapy.2008;2ndedition:760-65
4. R.S Sathoskar,S.D Bhandarkar,Nirmala N.Rege.Pharmacology
&Pharmacotherapeutics.2009;2nd edition:172-74.
5. P.N Bennet,M.J Brown.Clinical pharmacology.2003;9thedition:282-310
6. P.L Madan.Biopharmaceutics&Pharmacokinetics.2005;1stedition:105-20
7. D.M Brahmankar,Sunil B. Jaiswal.2009;2ndedition:345-47
8. Alfred Martin.Physical Pharmacy.2005:4thedition:486-88
9. Carsten EH Rhord,Kwang-Jin Kim.Drug Absorption Studies,in situ,in vivo & in
silico models.2010:90-106
10. The Merk Index.2001;13th edition:5322
11. CIMS.july –oct 2008:222
12. Ambade K.W,Jadhavu S.L,Gambhire, M.N,Kurmi S.Preparation & evaluation of
flubiprofen microemulsion.Current Drug Delivery 2008;5(1):32-41
13. Singh C,Jain K.A,Agarwal k,Nema R.K,Kumar
S,Kumar,Development,characterization & solubility study of solid dispersion of
terbinafine hydrochloride .Asian Journal of Pharmaceutics 2008;1(4):227-29
14. Appa Rao,B.M Shivalingam,Y.K Kishore Reddy.Formulation & evaluation of
aceclofenac solid dispersion.International Journal of Pharmaceutical Science &
Research 2010;2(2):146-150
15. Sahu Jagadish K,Banarjee Lopamudra.Evaluation of ulcerogenecity of ketoprofen
glucopyranoside derivatives.International Journal of Research in Ayurveda &
Pharmacy 2010;1(1):186-191
16. Amal H.E Kamal, Magda S. Sokar,Saffa S AL Gamal.Evaluation of stomach
protective activity of ketoprofen floating microparticles.Indian Journal of
Pharmaceutical Sciences 2003;5(2):399-401.
17. K.P.R Chowdary,K.V.V Suresh.Dissolution,bioavailability & ulcerogenecity on
indomethacin solid dispersion in water soluble cellulose polymer.Indian Journal
of Pharmaceutics 2005;4(2):112-115
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9.
Signature of the Candidate
10.
Remarks of the Guide
“FORMULATION OF SOLID DISPERSION OF KETOPROFEN & COMPARISON
OF ULCER INDEX OF KETOPROFEN SOLID DISPERSION WITH KETOPROFEN”
to be carried out by Mr.Sooraj Narayan of M. Pharm has been discussed and worked out
under my directions and supervision as an official guide. The project work envisaged is
of great importance in the field of Pharmaceutical Formulation. The work can be carried
out in Pharmaceutics &Pharmacology laboratory of Shree Devi College of Pharmacy for
which facilities are available. Hence the project is viable and is recommended for
clearance and approval.
11.
Name and Designation of
11.1 Guide
Mr.Ubaidulla
Assistant professor
Department of pharamaceutics
Shree Devi college of pharmacy
Mangalore.
11.2 Signature
11.3 Head of the Department
Dr.E.P Ezhil Muthu
Professor
Department of pharamaceutics
Shree Devi college of pharmacy
Mangalore.
11.4 Signature
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12.
12.1 Remarks of the Principal
The Programme and the Research work that is undertaking by Mr Sooraj Narayan have
potential implication in the field of Pharmaceutics. The work can be carried in the
Research Laboratories of Pharmaceutics & Pharmacology Department at Shree Devi
college of Pharmacy. Hence the Project is recommended and requested for clearance and
approval.
12.2 Signature
Prof. Dr. Jagadish V Kamath
Principal
Shree Devi college of pharmacy
Mangalore.
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