Analytical Method Development and Validation Of

Analytical Method Development and Validation Of

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF

ETODOLAC AND THIOCOLCHICOSIDE IN

PHARMACEUTICAL DOSAGE FORM

M. Pharm Dissertation Protocol Submitted to

Rajiv Gandhi University of Health Sciences, Karnataka

Bangalore – 560041

By

Ms. YASHI SRIVASTAVA,B.Pharm

Department of Quality Assurance

Under the Guidance of

SYED NIZAMUDDIN,M.Pharm

Asst. Professor

Department of Quality Assurance

Department of Quality Assurance,

Acharya B.M. Reddy College of Pharmacy,

Soldevanahalli,SarvepalliRadhakrishnan Road,

Hesaraghatta Main Road, Banglore-90.

2011-2013

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1.0 /

Name of the Candidate and Address

/ MS. YASHI SRIVASTAVA
D/o JP SRIVASTAVA
L-1372 Sector- I,
LDA Kanpur Road,
Lucknow,Uttar Pradesh.
2.0 / Name of the Institution / ACHARYA & B.M. REDDY COLLEGE OF PHARMACY,
Soldevanahalli, SarvepalliRadhakrishnan Road,
Hesaraghatta Main Road,
Bangalore,
Pin-560090.
3.0 / Course of Study and Subject / M.PHARMACY
QUALITY ASSURANCE
4.0 / Date of Admission / 18/6/2011
5.0 /

Title of the Topic

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF
ETODOLAC AND THIOCOLCHICOSIDE IN
PHARMACEUTICAL DOSAGE FORM
BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY:
ANALYTICAL METHODS:
Analytical methods are required to characterize drug substances and drug products composition during all phases of pharmaceutical development.Development of methods to achieve the final goal of ensuring the quality of drug substances and drug products must be implemented in conjunction with an understanding of the chemical behavior and physicochemical properties of the drug substance. Validation is a necessary and important step in both framing and documenting the capabilities of the developed method.
The present study is to make an attempt to establish a new, simple, sensitive, accurate and economical analytical method validation.
The present study is to make an attempt to establish sensitive and accurate methods for the estimation of Etodolac and Thiocolchicoside in pure and tablet dosage form.
The plan of the work as follows:
  1. Development of new analytical methods
  2. Assay of Etodolac and Thiocolchicoside tablet
  3. Accuracy studies
  4. Precision studies
  5. Stability studies
  6. Recovery studies
  7. Ruggedness and robustness
  8. Statistical evaluation
  9. Limit of detection and limit of quantitation
6.2 GENERAL DISCUSSION
ETODOLAC:
Etodolac is anon-steroidal anti-inflammatory drug(NSAID)with analgesic,anti- inflammatoryandantipyreticproperties1. It blocks the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower concentration of prostaglandins. As a consequence inflammation, pain and fever are reduced.

STRUCTURE OF ETODOLAC

/ .
IUPAC NAME / (±)1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid
MOLECULAR FORMULA / C17H21NO3
SOLUBILITY / Alcohols, Chloroform, Dimethylsulfoxide and Aqueous polyethylene glycol.
pKa / 4.65
Log P / 3.39
THIOCOLCHICOSIDE:
It is a muscle relaxant with anti- inflammatory and analgesic effects. It acts as a competitive GABA receptor antagonist and also inhibits glycine receptors2.
STRUCTURE /
IUPAC NAME / N-[(7S)-3-(beta-D-glucopyranosyloxy)-1,2-dimethoxy-10-(methylsulf​anyl)-9-oxo-5,6,7,9 tetrahydrobenzo[a]heptalen-7-yl]acetamide
SOLUBILITY / water and ethanol.
MOLECULAR FORMULA: / C27H33NO10S
6.3 REVIEW OF LITERATURE:
  1. Kousy reported onspectrophotometric and spectrofluorimetric methods of the anti-inflammatory drugs,etodolacand aceclofenac3.
  2. Madhusmita et al., reported RP HPLC PDA method for simultaneous estimation of Lornoxicam and Thiocolchicoside in pharmaceutical dosage form4.
  3. Sunitaet al., reported on HPTLC method for simultaneous estimation of Thiocolchicoside and Aceclofenac as the bulk drug and in tablet dosage forms. Chromatographic separation of the drugs was performed on aluminium plates precoated with silica gel 60 as stationary phase and the solvent system consisted of toluene: ethyl acetate: methanol: glacial acetic acid (4:6:2:0.5 v/v/v)5.
  4. Shekharet al., reported on reverse phase high pressure liquid chromatographic method has been developed for the simultaneous determination of Lornoxicam and Thiocolchicoside from tablets6.
  5. Arvindet al.,reported on stability indicating RP-HPLC method for the determination of Thiocolchicoside using C18 column (250mm × 4mm, 5μm) has been developed. A mobile phase consisting of acetonitrile: water (70:30) was used. The flow rate was 1.0 mL min-1 with UV detection at 286 nm7.
  6. Sureshet al., reported on simultaneous estimation of Etoricoxib (ETR) and Thiocolchicoside (THC) in bulk and combined tablet dosage form by liquid Chromatography8.
  7. Manojet al., reported on UV spectrophotometric and RP HPLC method development for simultaneous determination of paracetamol and etodolac in pharmaceutical dosage form.The first method was based on UV spectrophotometric determination of both the drugs, using simultaneous equation method. It involves absorbance measurement at 256nm (paracetamol) and 226nm (etodolac) in methanol; linearity was obtained in range of 5-25 micro gram per ml for both the drugs. The second method was based on HPLC separation of two drugs in reverse phase using promosil C18 column9.
6.4 OBJECTIVES OF THE STUDY:
Since only few methods have been reported in the literature for the quantitative estimation
ofEtodolac and Thiocolchicoside, there is scope for investigation of new analytical methods for Etodolac and Thiocolchicoside in bulk and pharmaceutical dosage forms. In view of the above facts, the present study was aimed to develop the following analytical methods for Etodolac and Thiocolchicosidewith high sensitivity, accuracy and precision.
To develop a RP-HPLC method for the simultaneous estimation of Etodolac and Thiocolchicosidedrugs in bulk & pharmaceutical Formulation.
To validate the RP-HPLC method developed, as per ICH guidelines, for parameters such as accuracy, precision, specificity, robustness, linearity etc.
To develop UV- spectrophotometric methods for the simultaneous estimation of Etodolac and Thiocolchicosidedrugs in bulk and pharmaceutical formulation.
To validate UV- spectrophotometric methods can be developed for its quantitative estimation in bulk and pharmaceutical formulation, as per ICH guidelines, for parameters such as accuracy, precision, specificity, robustness, linearity etc.
6.5 MATERIALS AND METHODS:
HPLC METHOD:
In the present investigation of new analytical methods for quantitative estimation of new drugs, we are using HPLC (shimadzu) with SPD 20A detector and other chromatographic instruments, UV-Visible double spectrophotometer (shimadzu 1700), the drug sample will be procured from various industries. All other chemical reagents will be procured from Qualigen, Merck and S.D.fine, chemicals Mumbai.
UV/VISIBLE SPECTROPHOTOMETRY:
UV/Visiblespectroscopy can be employed to identify & quantify the compoundspresent in most of the samples, present alone or in combination with other drugs. The limitation in this method is that it is less sensitive when compared to HPLC.
6.6 SOURCE OF DATA:
  1. JOURNALS
  • International Journal of Pharmaceutical Sciences
  • International Journal of Drug Development Research
  • International Journal of Chemical And Analytical Sciences
  • International Journal of Pharma and Biosciences
  • Indian Journal of Chemical Technology
  • International Journal of Research in Pharmacy and Chemistry
  • Journal of Chemical and Pharmaceutical Research
  • Journals like Indian Journal of Pharmaceutical Sciences
  • Journal of Chromatography
  1. WEB SITES
6.7 METHOD OF COLLECTION OF DATA:
  • All experiments shall be carried out in the Department of Quality Assurance, AcharyaB.M. Reddy College of Pharmacy,Bangalore-90.
  • Standard drug sample of etodolac and thiocolchicosude shall be procured from industries involved in the manufacture of these drugs or from suppliers.
  • The HPLC method shall be developed and validated in Department of Quality Assurance Lab of Acharya & B.M. Reddy College of Pharmacy, Bangalore-90.
  • Analytical abstracts and Chemical abstracts are collected from RGUHS and IISC library, Bangalore.
6.8 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON THE PATIENTS OR OTHER HUMAN/ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.
- Not Applicable -
6.9HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 6.8?
- Not Applicable-
6.10 LIST OF REFERENCES:
  1. Etodolac, O’Neil, Eds. M.J, The Merck Index, An Encyclopdia of Chemicals, Drugs and Biologicals, Merck & Co. Inc., Whitehouse Station, NJ, 2001;3871
  1. Thiocolchicoside, O’ Neil, Eds.M.J., The Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals, Merck & Co. Inc., Whitehouse Station, NJ, 2001;9328
  2. Kousy NMEI. Spectrophotometric and spectrofluorimetric determination of etodolac and aceclofenac.JPBA.1999;20(1,2):185-94
  3. Madhusmita S, Pratima S, Snehal I, Kunal I, Santosh S, Monali S, Choudhari VP, Kuchekar BS. Development and validation of RP HPLC PDA method for simultaneous determination of lornoxicam and thiocolchicoside in pharmaceutical dosage form and its application for dissolution study.IJRPS.2011; 2(1):1-7
  4. Sunita TP, VidhyaKB Sunil RD. Validated HPTLC method for simultaneous estimation of thiocolchicoside and aceclofenac in bulk drug and formulation. IJPBS. 2011;2(2):482-90
  5. Shekhar MB.Development and validation of analyticalmethod for the determination of lornoxicamand thiocholchicoside in pharmaceuticaldosage form by reversed-phase hplc.JCPR.2010;2(2):563-72
  6. Arvind R U, Niki SR, Dinesh RC, Lokesh TT, Sunil B C, Mayur RB. Stability indicating RP-HPLC method for estimation of thiocolchicoside in capsule dosage forms.RJPBCS.2011;2(1):750-56
  7. Suresh KS, Natraj D, Asadulla K, Kalyan KB and venkateswaraRJ.Simultaneous estimation of etoricoxib and thiocolchicoside in pharmaceutical dosage forms. IJRPC.2011;1(3): 649-53
  8. Manoj KJ,DR.UL narayana.UV spectrophotometric and RP HPLC method development for simultaneous determination of paracetamol and etodolac in pharmaceutical dosage form;Available from URL:
  9. H.P. Rang, M.M. Dale, J.M. Ritter, R.J. Flower., Rang and Dale’s Pharmacology, 6thEdn., Churchill Livingstone Elsevier, 227-28

7.0 / SIGNATURE OF THE
CANDIDATE
8.0 / REMARKS OF THE GUIDE / Recommended for Research
9.0 / NAME AND DESIGNATION OF:
9.1 GUIDE / SYED NIZAMUDDIN
Asst. Professor,
Department of Quality Assurance,
Acharya & B.M. Reddy College of Pharmacy, Soldevanahalli,SarvepalliRadhakrishnan Road,Hesaraghatta Main Road, Bangalore-90.
9.2 SIGNATURE
9.3 CO-GUIDE / ------
9.4 SIGNATURE / ------
9.5 HEAD OF THE DEPARTMENT / Prof. A. Cendilkumar,
Department of Quality Assurance,
Acharya & B.M. Reddy College of Pharmacy, Soldevanahalli,SarvepalliRadhakrishnan Road,Hesaraghatta Main Road, Bangalore-90.
9.6 SIGNATURE
10.0 / 10.1 REMARKS OF THE PRINCIPAL
10.2 NAME OF THE PRINCIPAL / Dr. DivakarGoli,
Principal,
Acharya & B.M. Reddy College of Pharmacy, Soldevanahalli,, SarvepalliRadhakrishnan Road,Hesaraghatta Main Road, Bangalore-90.
10.3 SIGNATURE