“DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE ESTIMATION OF CICLOPIROX OLAMINE AND TERBINAFINE HYDROCHLORIDE”

M.PHARM DISSERTATION PROTOCOL

Submitted to the

RAJIVGANDHIUNIVERSITY OF THE HEALTH SCIENCES, KARNATAKA

BANGALORE

By

SOJITRA PRADIPKUMAR KHODABHAI

B.Pharm

UNDER THE GUIDANCE OF

G M SREENIVASA,

M.Pharm

ASSISTANT PROFFESOR,

P. G. DEPARTMENT OF QUALITY ASSURANCE

S.C.SCollege of Pharmacy, Harapanahalli-583131

KARNATAKA

2010

RajivGandhiUniversity of Health Sciences, Karnataka, Bangalore

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

01 / Name and Address of the Candidate / SOJITRA PRADIPKUMAR KHODABHAI
13, SARITA SAGAR SOC;
B/H HARIKUNJ SOC; CHIKUWADI,
NANA VARACHHA,
SURAT.-395006
GUJARAT.
02 / Name of the Institution / T. M. A.E. Society’s
S.C.S.College of Pharmacy,
Harapanahalli- 583 131
03 / Course of the Study
Branch / M. Pharm.,
Quality Assurance
04 / Date of Admission to Course / 3rd Sept.- 2009
05 / Title of the Topic / “DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE ESTIMATION OF CICLOPIROX OLAMINE AND TERBINAFINE HYDROCHLORIDE”
06 / Brief Resume of the intended work
6.1 Need for the Study /
Enclosure- I
6.2 Review of the literature / Enclosure – II
6.3 Objective of the Study / Enclosure – III
07 / Materials and Methods
7.1 Source of Data / Enclosure – IV
7.2. Methods of collection of data / Enclosure – V
7.3 Does the study require any
Investigation on animals?
If yes give details / Enclosure - VI
-NO-
7.4. Has ethical clearance been
obtained from your institution
In case of 7.3. / -NOT APPLICABLE -
08 / List of References / Enclosure – VII
09 / Signature of the Candidate / ( SOJITRA PRADIPKUMAR KHODABHAI )
10 / Remarks of the Guide / The present research work is original and not published in any of the journals with best of my knowledge upon extensive literature review. This work will be carried out in the Dept. of Quality Assurance laboratory by the above said student under my supervision.
11 / Name and Designation of
( In Block Letters )
11.1 Guide
ACA/CDC/PGT-M.ph/SCS/02/2005-06/19.01.09.
11.2 Signature
11.3 Co-Guide
ACA-2/RP-TEA/O1/97-98/3-9-98
11.4 Signature
11.5. Head of the Department
Signature / Mr.G. M.SREENIVASA
M.Pharm.
ASSISTANCE PROFESSOR,
S.C.S.COLLEGEOF PHARMACY,
HARAPANAHALLI- 583 131,
DIST.- DAVANGERE
Dr. E.JAYACHANDRAN
PROFESSOR & HEAD,
DEPT. OF PHARMACEUTICAL CHEMISTRY, S.C.SCOLLEGE OF PHARMACY
HARAPANAHALLI-583131.
DIST. - DAVANGERE.
Dr.R.NAGENDRA RAO
PROFESSOR & HEAD,
DEPT. OF QAULITY ASSURANCE,
S.C.S.COLLEGE OF PHARMACY,
HARAPANAHALLI -583131
12 / Remarks of the Principal
Signature / The candidate has been permitted to carry
Out the said above mentioned title in the Dept. Of Quality assurance.
PROF. K.PRABHU
Principal
S.C.S.College of Pharmacy
Harapanahalli-583131
KARNATAKA

ENCLOSURE - I

6. BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY

Ciclopirox Olamine and terbinafine hydrochloride are antifungal drugs which are clinically effective in the treatment of Dermatophytosis in human.It is caused by fungi of several different species. The fungi that cause parasitic infection (dermatophytes) feed on keratin, the material found in the outer layer of skin, hair, and nails. These fungi thrive on skin that is warm and moist, but may also survive directly on the outsides of hair shafts, or in their interiors1-2.

Validation of analytical methods is of critical importance as it is the cornerstone of process validation. An attempt has been made to develop and validate a simple, economic, rapid and accurate method. Here some simple and sensitive extractive methods mentioned to estimate both drugs3-13

  1. Derivative spectrophotometry
  2. Difference spectrophotometry
  3. Assay as a single-component sample
  4. Simultaneous equation method
  5. Geometric correction method
  6. Ion-Pair complexformation
  7. Ratio Spectra Method
  8. Least square approximation
  9. Colorimetric method
  10. Area under curve method

Ciclopirox is a synthetic antifungal agent for topical dermatologic use. Its chemical name is 6-cyclohexyl-1-hydroxy-4-methylpyridin-2-one and 2-aminoehanol. Its chemical formula is C12H17NO2 · C2H7NO

It contains

Ciclopirox (C12H17NO2; Mol Wt- 207.3): 76.0 per cent to 78.5 per cent (dried substance).

2-aminoethanol (C2H7NO; Mol Wt- 61.1): 22.2 per cent to 23.3 per cent (dried substance)14

Ciclopirox olamine is a synthetic broad spectrum antifungal agent that inhibits the growth ofpathogenic dermatophytes, yeasts, and Malassezia furfur. Ciclopirox olamine exhibitsfungicidal activity in-vitro against isolates of Trichophytonrubrum, Trichophyton

mentagrophytes, Epidermophytonfloccosum, Microsporumcanis, and Candida albicans.

Ciclopirox Olamine is thought to act through the chelation of polyvalent metal cations, such as Fe3+ and Al3+. These cations inhibit many enzymes, including cytochromes, thus disrupting cellular activities such as mitochondrial electron transport processes and energy production. Ciclopirox also appears to modify the plasma membrane of fungi, resulting in the disorganization of internal structures. The anti-inflammatory action of ciclopirox is most likely due to inhibition of 5-lipoxygenase and cyclooxygenase.15

Ciclopirox Olamine is available in cream, lotion, shampoo and solution.

Terbinafine hydrochloride (Lamisil) is a synthetic allylamine antifungal. It is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues. Its chemical name is N,6,6-trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine and chemical formula C21H25N

It is used for the treatment of interdigitaltinea infections and is hypothesized to act by inhibiting squaleneepoxidase, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes.16

Terbinafine is available in cream, spray and tablet.

ENCLOSURE – II

6.2 REVIEW OF LITERATURE:

The review of various published work related to subject and objectives of the study has revealed the following:

  • Cardoso SG, Schapoval EE.; UV Spectrophotometry and Nonaqueous Determination of Terbinafine Hydrochloride in Dosage Forms. J AOAC Int. 1999 Jul-Aug; 82(4):830-3.
  • Lakshminarayana KV, Manohara YN, Gurupadayya BM, Development and validation of spectrophotometric methods for the estimation of nitazoxanide in tablet dosage forms. Ind. J. of Ph. Sci.,Year: 2007,Vol:69,Issue:1Page : 147-149
  • Walash M.I.; Rizk M.S.; Iibrahim Eid M; Fathy M.E.;Spectrofluorimetric Determination of CiclopiroxOlamine via Ternarycomplex with Tb(III)and EDTA.Acta Pharmaceutica;Vol.56 No.4 Dec2006, Page .431
  • Gowri Sankar D*, Joy Babu P, Anil Kumar B and Madhavi Latha P V; Spectrophotometric Determination of Aceclofenac and Famciclovir. Int. J. of Chem. Sci; Vol.4 (3):2006, 725-728.
  • El-Saharty YS, Hassan NY, Metwally FH.; Simultaneous Determination of Terbinafine HCL and Ttriamcinolone Acetonide by UV derivative spectrophotometry and spectrodensitometry. J Pharm Biomed Anal. 2002 May 15;28(3-4):569-80.
  • Pandey V P, Vanjnathan S, and Stella Singh; Determination of Domperidone and Omeprazole in Capsule Dosage form by UV/Visible Spectrophotometer. Asian J. of Chem; Vol.22, No.3 (2010), 2305-2308.
  • Abdel-Moety E M,Kelani K O, Abou al-Alamein A M;Spectrophotometric determination of Terbinafine in presence of its Photodegradation products,J Pharm Biomed Anal. 2002 Nov 7;30 (4):1023-33

[My paper]ENCLOSURE-III

6.3 MAIN OBJECTIVE OF THE STUDY

The present work is in an attempt to:

  1. To develop selective, precise and sensitive method for the development and estimation of the Cilcopirox olamineand Terbinafine Hydrochloride.
  2. The analytical method so far developed is to be validated.
  3. The work involves use of analytical techniques such as Spectroscopy.
  4. The method appears to be suitable for the quality control in pharmaceutical industry.

ENCLOSURE-IV

7. MATERILAS AND METHODS

7.1 SOURCE OF DATA.

The preliminary data required for the experimental study was obtained form

  1. British Pharmacopoeia 2009
  2. Chemical sources
  3. Scientific sources
  4. Journals
  5. Internet sources
  • From the helinet service of RGUHS, Bangalore.
  1. Relevant books
  2. Library, S.C.SCollege of Pharmacy

ENCLOSURE-V

7.2METHODS OF COLLECTION OF DATA

Data pertaining for the present study will be obtained from Quality Assurance Laboratory of S.C.S College of Pharmacy, Chemical abstracts, Scientific abstracts, Journals and Internet sources etc..,

ENCLOSURE - VI

7.3Does the study require any investigation to be conducted on patients/ Humans/ Animals? If so describe briefly

Not Applicable

7.4 Has ethical clearance been obtained from your institution in case of 7.3?

Not Applicable

7.5 METHODOLOGY:

  • The experimental and spectral data pertaining for the present study is obtained from the various techniques adopted in the estimation of cefotaxime & ceftriaxone, in pharmaceutical preparation.
  • The Spectrophotometric method shall be developed and validated in Q.A. lab of S.C.S.College of pharmacy.
  • The study does not require any investigation on patients or humans or animals.

ENCLOSURE – VII

9. LIST OF REFERENCES:

  1. accessed on the date 26 May-2010
  1. Goodman & Gilman’s the Pharmacological basis of Therapeutics - 11th Ed.2006,
    Chapter 48: Antimicrobial Agents: Antifungal Agents.HTML.
  1. Mahmoud Chamsaz, Mohammad HosseinArbabzavar, Tahereh, heidari* and Akram
    Hajinia. Spectrophotomertic Determination of Trace Amounts of Beryllium in
    Water using Mean Centering of Ratio Spectra Method and Partial Least Squares
    Regression. Asian J. of Chem.2010, Vol.22, No.6, 4717-4726.
  2. PatilShamkant*, DhabalePandurang andKuchekarBhanudas; Development and
    Statistical Validation of Spectrophotometric Method for Estimation of
    Esomeprazolein Tablet Dosage Form.Asian J. Research Chem. April.-June,

2009, Vol. 2(2)

  1. ManikyaSastry T., Trilochan Padhi and Ramakrishna K; Development and
    Validation of Spectrophotometric Method for the Determination of Abacavir
    Sulphate in Bulk and Pharmaceutical formulations. Int. J. Chem Sci,
    2009, Vol: 7(2), 1053-1060.
  1. BalaSekaran C*, and Prameela Rani A.; Development and Statistical Validation of
    Spectrophotometric Methods for the Determination of ACE Inhibitor in
    Pharmaceutical formulation. Int. J. Chem, 2009 Sci.:7(2), 1153-11558.
  1. Ivana Savić1, Goran Nikolić1, Vladimir Banković; Development and Validation of
    Spectrophotometric Method for Phenylephrine Hydrochloride estimation in Nasal
    Drops formulation.Macedonian Journal of Chemistry and Chemical Engineering,
    2008 Vol. 27, No. 2, , 149–156
  1. Maheshwari P, AppalaRaju S and SobhaManjunath. Development and Validation of
    Spectrophotometric Methods for the Estimation of Balsalazide in bulk and
    Pharmaceutical formulation. Int. J. Chem.2009, Sci.: 7(2), 1249-1254.
  1. EmirhanNemutlu* / SedefKır, Validated Determination of Meloxicam in Tablets by
    Using UV Spectrophotometry, Hacettepe University, Journal of Faculty of
    Pharmacy, January 2004, Vol. 24, No.1, 13-24.
  1. Lakshminarayana KV, Manohara YN, Gurupadayya BM; Development and
    validation of spectrophotometric methods for the estimation of nitazoxanide in
    tablet dosage forms. Ind. J. of Pharm Sci; Year: 2007, Vol: 69 Issue: 1, Page: 147-
    149.
  1. Various UV spectrophotometric Simultaneous estimation methods, Pharmainfo.net,
    2006, Vol- 4, issue -2.
  1. Ravindra N and Shingvi I; Spectrophotometric Method for the Estimation of
    Aripirazole from Pharmaceutical Dosage form. Int. J. of Chem. Sci; 2006,
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  1. Lakshmi KS, Ilango K, NithyaMathi N, Balaji S, Kige D, Victor Wathugi and
    Sathish Kumar V; Visible Spectrophotometric Method for the Determination of
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    Pharmaceutical Substances, Ciclopirox Olamine, 1302.
  1. Drug Bank- Drug card for Ciclopirox (DB01188) from
  1. Drug Bank - Drug card forTerbinafine (DB00857) from

1