RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF Subjects FOR DISSERTATION

1. / Name of the Candidate and
Address (in block letters) / ABDUL FAHEEM,
5-993/20/56, OMER COLONY, AZADPUR ROAD GULBARGA-585104 (KARNATAKA)
2. / Name of the Institution / H.K.E.S’S College of Pharmacy, Sedam Road, GULBARGA-585105 (Karnataka)
3. / Course of Study and Subject / M. Pharm. (Pharmaceutical Analysis)
4. / Date of Admission to Course / 24.06.2008
5. / Title of the Topic / “DEVELOPMENT OF NEW ANALYTICAL METHODS FOR ESTIMATION OF SOME OPIOID ANTAGONIST”
6. / BRIEF RESUME OF THE INTENDED WORK
6.1 Need for the Study
Naltrexone is an orally available opioid receptor antagonist that blocks the effect of exogenous and presumably, endogenous opioids. It is official in United State Pharmacopoeia (USP) and British Pharmacopoeia. Investigations of some new instrumental methods are in need for the quantitative estimation of naltrexone in bulk drug and pharmaceutical dosage forms with high sensitivity, accuracy, precision and economical too.

6.2 Review of Literature

Naltrexone1-4 is chemically (5α)-17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-one.The molecular formula for naltrexone is C20H23NO4, its molecular weight is 341.40. Its melting point is 168-170°C. It is soluble in water.
As Naltrexone is used in the treatment of alcoholism and as narcotic antagonist. Naltrexone is metabolized mainly to 6β- naltrexone by liver dihydrodiol dehydrogenase 5.
There are few methods of determination of naltrexone, A LC electrospray Tandem MS method for the analysis of naltrexone in canine plasma employing a molecular model to demonstrate the absence of internal standard deuterium isotope effects6. Nano level detection of naltrexone hydrochloride in its pharmaceutical preparation at Au microelectrode in flowing solutions by fast fourier transforms continuous cyclic voltammetry as a novel detector7.

Naltrexone
6.3 Objectives of the Study
Since no analytical methods have been reported for the quantitative estimation of naltrexone, there is a necessity for investigation of new instrumental methods for quantitative estimation of naltrexone in bulk drug and pharmaceutical dosage forms (tablets). In view of the above facts, the following instrumental methods are planned to develop.
i) Since the drug naltrexone is sufficiently soluble in methanol, ethanol, water and dilute alkalis, a number of UV-spectrophotometric methods can be developed for its quantitative estimation in bulk drug and pharmaceutical dosage forms.
ii) Since the drug is having phenolic group, it can form colored chromogens with phosphomolybdo tungstic acid, well known as Folin-Ciocalteu reagent
(FC reagent) in alkaline pH by redox reaction which can be used for quantitative estimation of naltrexone in bulk drug and pharmaceutical dosage forms by visible spectrophotometry.
iii) Presence of phenolic group in naltrexone allows the oxidative coupling reaction with 3-methyl-2-benzothiazolinone hydrazone (MBTH) (II) in presence of ceric ammonium sulphate and forms colored chromogen (III) by which drug can be estimated quantitatively by visible spectrophotometry.

Colored chromogen
iv) The phenolic hydroxy group in drug molecules reacts with ferric salt (ferric chloride) in aqueous, alcoholic or chloroform media to give intense coloration characteristic of the drug. The color is due to the strongly ionised complex, phenolate of trivalent iron. The colored chromogen (IV) formed can be utilised for quantitative estimation of drug by visible spectrophotometry.

. / FeCl3 + 6 ROH 6H+ + 3Cl- + [ Fe(OR)6]3-
(I) (IV)
Colored chromogen

v) Since the drug is having phenolic group, it form colored complex (VII, VIII) with 1,10-phenanthroline and 2,2’-bipyridine in presence of Fe(III) which can be utilized for quantitative estimation of naltrexone in bulk drug and pharmaceutical dosage from colorimetrically.

vi) Since drug is having phenolic group, it forms coloured chromogen (VI) with Gibb’s reagent (2,6-dichloroquinone chlorimide (V) in alkaline pH which can be utilised for quantitative estimation of drug by visible spectrophotometry in bulk drug and pharmaceutical dosage forms.

vii) Reversed phase high performance liquid chromatographic techniques can be developed using a gradient HPLC (Shimadzu HPLC Class VP series 6.01) with two LC-10 AT VP Pumps, variable wave length programmable UV/visible detector for quantitative estimation of naltrexone in bulk drug and pharmaceutical dosage forms with high sensitivity, accuracy, precision and which are economical too.
7. / MATERIALS AND METHODS
In the present investigation of the new instrumental methods for quantitative estimation of Naltrexone, we are in need and using Shimadzu 1700 double beam UV/visible spectrophotometer, HPLC (Shimadzu, Class VP series 6.01), chromatographic instruments and volumetric glass apparatus. Drug sample will be provided by Intas Pharmaceutical, Ahmedabad.
7.1 Source of Data
a. Internet, Library
b. Gulbarga University, Gulbarga
c. I.I.Sc. Library, Bangalore
d. I.I.C.T. Library, Hyderabad
e. R.G.U.H.S. Library, Bangalore.
7.2 Methods of collection of data (including sampling procedures, if any)
Data Collected From
i) Internet: H.K.E.S’s College of Pharmacy, Gulbarga.
ii) Analytical Abstracts and Chemical Abstracts – Gulbarga University, I.I.Sc. and I.I.C.T. Libraries.
iii) Journals like – Indian J. Pharmaceutical Sciences, Indian Drugs and Indian J. Analytical Chemistry.
iv) e-Journals.
v) Drug sample of naltrexone will be collected from Intas Pharmaceutical, Ahmedabad.
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
---- No ----
7.4 Has ethical clearance been obtained from your institution in case of 7.3.
---- Not Applicable ----
8. / Referances:
1. O’ Neil MJ, editor, The Merck Index: An Encyclopedia of Chemicals, Drug, Biologicals, 14th edn. Merck & Co. Inc.: 2006: p. 1101.
2. Sweetman SC, editor, Martindale: The Complete Drug Reference, 35th edn. Pharmaceutical Press, London: 2007: p. 1310.
3. The United State Pharmacopeial Convection, editor, United State Pharmacopeia. NF, asian edn. 2007; 03: p. 2703-4.
4. British Pharmacopoeia, Medicines and Health care products regulatory agency (MHRA), London, 2008; 2: 1512-13.
5. Bertam G Katzung, editor, Basic and Clinical Pharmacology, 9th edn. Mc. Graw Hill, singapore, 2007: p. 375-7,512-4.
6. Iyer, Sunil S, Kellogg, Glen E, Karnes, Thomas H. A LC electrospray Tandem MS method for the analysis of naltrexone in canine plasma employing a molecular model to demonstrate the absence of internal standard deuterium isotope effects, J Chromatographic Sci, 2007;45: 694-700.
7. Norouzi P., Ganjali MR, Zare M, Mohammadi A. Nano level detection of naltrexone hydrochloride in its pharmaceutical preparation at Au microelectrode in flowing solutions by fast fourier transforms continuous cyclic voltammetry as a novel detector. American Pharmacists Association J pharm Sci. 2007:96:2009-17.
9. / Signature of Candidate / ABDUL FAHEEM
10. / Remarks of the Guide / The work undertaken will be Novel & Industrial oriented. The work will be new Resrech findings. All facilities are available to undertake the work.
11. / Name & Designation of (in block letters)
11.1 Guide
11.2 Signature / Mr. PRAKASH S. SARSAMBI, M.Pharm
Assistant Professor
DEPT. OF PHARMACEUTICAL ANALYSIS, H.K.E.S COLLEGE OF PHARMACY, GULBARGA
11.3 Head of the Department
11.4 Signature / DR. S. M. MALIPATIL, M.Pharm,Ph.D
PROFESSOR
DEPT. OF PHARMACEUTICAL ANALYSIS, H.K.E.S COLLEGE OF PHARMACY, GULBARGA
12. / 12.1 Remarks of the Chairman
& principal
12.2 Signature