“DEVELOPMENT OF NEW ANALYTICAL METHODS FOR THE ESTIMATION OF DEFERASIROXIN BULK DRUG AND PHARMACEUTICAL FORMULATION”

M. Pharm Dissertation Protocol

Submitted to

RajivGandhiUniversity Of Health Sciences, Bangalore, karnataka

chaitanya.sOOram

Under the guidance of

Mr.PRAKASH.S.SARSAMBI M.Pharm

DEPARTMENT OF PHARMACEUTICAL ANALYSIS

H.K.E.S’SCOLLEGE OF PHARMACY,

SEDAMROAD,GULBARGA – 585105

2010-2011

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES, KARNATAKA,BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF Subjects FOR DISSERTATION

1. / Name of the Candidate and
Address (in block letters) / CHAITANYA. SOORAM. D/O RAGHOTHAM REDDY, H:NO 2-12-360/1 OPP TO K.U.C II GATE,VIDYARANYAPURI,HANMAKONDA,
PIN:506001,WARANGAL.DISTRICTANDHRAPRADESH.
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 / 18-06-2010
5 / Title of the Topic. / “DEVLOPMENT OF NEW ANALYTICAL METHODS FOR THE ESTIMATION OF DEFERASIROX IN BULK DRUG AND PHARMCEUTICAL FORMULATION”
6. / BRIEF RESUME OF THE INTENDED WORK
6.1 Need for the Study
Deferasirox is an orally available drug showing anantidote action. Deferasiroxis an orally active iron chelator belonging to a new class of tridentate iron chelator, The N –substituted bis hydroxyl phenyl –triazoles.Deferasirox has a very low affinity for zinc and copper there are variable decrease in the serum concentration of these trace metals after the administration of Deferasirox.
There is a wide scope for the development of new analytical methods for the assays of Deferasirox. Investigation of some new instrumental methods is in need for the quantitative estimation of Deferasirox in bulk drug and pharmaceutical dosage forms with high sensitivity, accuracy, precision and economical too.

6.2Review of Literature

Deferasirox1-2 is chemically4-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-Triazol-1-yl]benzoic acid. It isofficial in United States Pharmacopoeia3. The Molecular formula for Deferasirox is C21H15N3O4,Molecular weight is 373.4,and Melting point is 264-265oC. It soluble in water, methanol, ethanol, Literature Survey reveals that few physico chemical methods are reported for Deferasirox(concerned with biological fluid sample). i.e., A method to measure deferasirox in plasma using HPLC coupled with MS/MS detection and its potential application4. A stability indicating LC method for Deferasirox in bulk drugs and pharmaceutical dosage forms5-6.The structural formula for Deferasirox is as below

(I)
Deferasirox
6.3 Objectives of the Study
The analytical important function groups of the Deferasirox has not been completely exploited for designing sensitive,precise, accurate and flexible spectrophotometric methods for the determination of Deferasirox in bulk drug and pharmaceutical formulations. Hence, with the above mentioned fact the following instrumental methods are planned to develop.
(i)Since the drug Deferasirox is sufficiently soluble in water, methanol, ethanol, 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 tungsten acid, well known as Folin-Ciocalteu reagent
(FC reagent) in alkaline pH by redox reaction which can be used for quantitative estimation of Deferasirox in bulk drug and pharmaceutical dosage forms by visible spectrophotometry.
(iii)Presence of phenolic group in deferasirox allows the oxidative coupling reaction with 3-methyl-2-benzothiazolinone hydrazone (MBTH) (II) in presence of cerric ammonium sulphate or ferric chloride and forms colored chromogen(III) by which drug can be estimated quantitatively by visible spectrophotometry.

(III)
(iv)The phenolichydroxyl 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 ionized complex, phenolate of trivalent iron. The colored chromogen (IV) formed can be utilized for quantitative estimation of drug by visible spectrophotometry.
FeCl3 + 6 R-OH 6H+ + 3Cl- + [ Fe(OR)6]3-
(I) (IV)
Colored chromogen

(v)Since the drug is having phenolic group, it form colored complex (V, VI, VII) with 1, 10-phenanthroline, 2, 2’-bipyridyl and potassium ferricyanide in presence of Fe (III)which can be utilized for quantitative estimation of Deferasirox in bulk drug and pharmaceuticaldosage from colorimetrically.

Deferasirox+Fe(III) oxidation products+ Fe(II)+unreacted Fe(III)
3Fe+2+2[Fe(CN)6]-3 Fe3[Fe (CN)6] 2
Blue color(VII)
(vi)Since drug is having phenolic group, it forms colored chromogen (IX) with Gibb’s reagent (2, 6-dichloroquinone chlorimide) (VIII) in alkaline pH which can be utilized 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 or isocratic RP- 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 Deferasirox 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 we are in need of 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 Novartis pharma Ltd. India
7.1 Source of Data
a. Internet, Library
b. GulbargaUniversity, 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 – GulbargaUniversity, I.I.Sc. and I.I.C.T. Libraries.
iii) Journals like – Indian J. Pharmaceutical Sciences, Indian Drugs Indian J. Analytical Chemistry. Pharma review and Asian J.Chemistry.
iv) E-Journals.
v) Drug sample of Deferasirox will be collected from Novartis Pharma Ltd India.
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. / References:
  1. O’ Neil M.J, editor. The Merck Index: An Encyclopedia of Chemicals, Drug and Biologicals.14th edn, Merck & Co. Inc: 2006;483.
  1. SweetmanSC, editor. Martindale: The Complete Drug Reference, 35th edn, Pharmaceutical Press: London(U.K): 2007; 1294.3.
  1. United States pharmacopoeia,31st edn. United States PharmacopeialConvention, RockvilleUSP (2008).
  1. Chauzit E, Bouchet S, Micheau M, Mahon FX, Moore N, Titier K and Molimard MA Method to measure deferasirox in plasma using HPLC coupled with MS/MS detection and its potential application.Chromatographia Ther Drug Monit. Aug 2010 ;32(4):476-481.
  1. Ravi Kiran Kaja, Surendranath K.V, Radhakrishnanand P, Satish J and Satyanarayana P.V.V A Stability Indicating LC Method for Deferasirox in Bulk Drugs and PharmaceuticalDosage Forms.J.of Chromatographic.Nov.2010.72(5):441-446.
  1. Jens T. Carstensen, Rhodes CT(eds),Drug stability principles and practices. 3rd edn. Marcel Dekker, New York.(2000).

9. / Signature of Candidate / CHAITANYA. SOORAM
10. / Remarks of the Guide / The work undertaken will be novel and industrial oriented. The work will be new research findings. All facilities are available in our college to undertake the work.
11. / Name & Designation of (in block letters)
11.1Guide
11.2 Signature / Mr. PRAKASH S. SARSAMBI, M.Pharm
Assistant Professor
DEPT. OF PHARMACEUTICAL ANALYSIS,H.K.E.S’S COLLEGE OF PHARMACY
GULBARGA.
11.3Head of the Department
11.4 Signature / DR. S.M.MALIPATIL,M.Pharm,Ph.D.
PROFESSOR
DEPT. OF PHARMACEUTICAL ANALYSIS, H.K.E.S’S COLLEGE OF PHARMACY,GULBARGA.
12. / 12.1 Remarks of the Chairman
& principal
12.2 Signature