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

M. Pharm Dissertation Protocol

Submitted to

RajivGandhiUniversity Of Health Sciences,Bangalore, karnataka

By

a.n.reddy tippiredDY

Under the guidance of

Dr.S.APPALARAJU M.Pharm.Ph.D

DEPARTMENT OF PHARMACEUTICAL ANALYSIS

H.K.E.S’sCOLLEGE OF PHARMACY,

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) / A.N.REDDY TIPPIREDDY,
S/O VENKATARAMIREDDY.T,
19/27 DWARAKANAGAR,PIDUGURALLA 522413,GUNTUR DISTRICT,A.P.
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 DESVENLAFAXINE IN BULK DRUG AND PHARMCEUTICAL FORMULATION”.
6. / BRIEF RESUME OF THE INTENDED WORK
6.1 Need for the Study:
Desvenlafaxineis an antidepressant drug used in major depressive disorders.It is available as extended release 50 and 100 mg tablets. It is not official in any pharmacopoeia. Since analytical methods are not available for its quantitative estimation in bulk drug and pharmaceutical formulations (tablets),there is a need to develop simple,sensitive, accurate, precise and economical instrumental methods for its quantitative estimation in bulk drug and pharmaceutical formulations (tablets).

6.2Review of Literature

Desvenlafaxine is an antidepressant drug used in major depressive disorders1. Desvenlafaxine is chemically 4-[2-dimethylamino-1-(1-hydroxycyclohexyl)ethyl] phenol with molecular weight 263.375 g/mol and molecular formula C16H25NO2. It is available as tablet formulations in the market.It is a white crystalline powder.It is soluble in water2-7.No analytical method found for its quantitative estimation in bulk drug and pharmaceutical formulations in literature.It is not official in any pharmacopoeia.

Desvenlafaxine(I)
i)
ii) / 6.3 Objectives of the Study
The important functional groups of the desvenlafaxinefor analytical purpose have not been completely exploited for designing sensitive,precise, accurate and economical spectrophotometric methods for the determination of desvenlafaxinein bulk drug and pharmaceutical formulations.In view of the above mentioned fact the following instrumental methods are planned to develop.
Since the drug desvenlafaxineis sufficiently soluble in water, methanol and ethanol, a number of UV-spectrophotometric methods can be developed for its quantitative estimation in bulk drug and pharmaceutical dosage forms.
The drug is having phenolic group, it can form colored chromogens with phosphomolybdotungsticacid, well known as Folin-Ciocalteu reagent
(FC reagent) in alkaline pH by redox reaction which can be used for quantitative estimation of desvenlafaxinein bulk drug and pharmaceutical dosage forms by visible spectrophotometry.
iii)
iv) / Presence of phenolic group in desvenlafaxineallows the oxidation followed by coupling reaction with 3-methyl-2-benzothiazolinone hydrazone (MBTH) (II) in presence of cerric- ammoniumsulphate or ferric chloride to form colored chromogen(III) by which drug can be estimated quantitatively by visible spectrophotometry.

The phenolic group in drug molecules reacts with ferric salt (ferric-chloride) in aqueous, alcoholic or chloroform media to give intense colorationcharacteristic ofthe drug. The color is due to the strongly ionized complex, phenolate of trivalent ion. The colored chromogen (IV) formed can be utilized for quantitative estimation of drug by visible spectrophotometry.
v) / FeCl3 + 6 ROH 6H+ + 3Cl- + [ Fe(OR)6]3-
(I) (IV)
Colored chromogen

Since the drug is having phenolic group, it may form colored complexes (V, VI, VII) with 1, 10-phenanthroline, 2, 2’-bipyridine and potassium ferricyanide in presence of Fe (III) by oxidation followed complex formation reactionwhich can be utilized for quantitative estimation of desvenlafaxinein bulk drug and pharmaceutical dosage form colorimetrically.

vi)
vii) / Desvenlafaxine+Fe(III) oxidation products+ Fe(II)+unreacted Fe(III)
3Fe+2+2[Fe(CN)6]-3 Fe3[Fe (CN)6] 2
Blue color(VII)
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.

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 desvenlafaxine in bulk drug and pharmaceutical dosage forms with high Sensitivity, accuracy, precision and economical too.
7. / MATERIALS AND METHODS
In the present investigation we are in need of using Shimadzu 1800 double beam UV/visible spectrophotometer, HPLC (shimadzu, Class VP series 6.01), chromatographic instruments and volumetric glass apparatus. Drug sample and formulations are provided by Zydus Neuro sciences.
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 and Indian J. Analytical Chemistry.
iv) E-Journals.
v)Drug and formulation samples collected from Zydus Neuro sciences.
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. Cims,CMP Media India Private Limited,2010,109,15.
  1. LourencoMT et.al.,Neuro psychiatr.Dis.Treat.2009,5,127-136.
  1. Andrede C.Indian J.Psychiatry,2009,51,320-323.
  1. DeecherDC et.al.J.Pharm.Exp.Ther,2006,318,657-665.
  1. Richards LS. Clin.pharmacol.Ther.2006, 79.
  2. Perry R et.al. Clin.Ther,2009,31,1374-1404.
  1. Reddy S et.al. Curr.Med.Res.Opin.2010,26(1),139-150.

9. / Signature of Candidate / A.N.REDDY.TIPPIREDDY
10. / Remarks of the Guide / The work undertaken is novel and may
result in new research findings.
11. / Name & Designation of (in block letters)
11.1Guide
11.2 Signature / Dr. S.APPALARAJU, M.Pharm.Ph.D
PRINCIPAL, H.K.E.S’sCOLLEGE 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