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Simultaneous estimation of etoricoxib and paracetamol in combined tablet dosage form

Authors:
  • Priyadarshni J. L. college of Pharmacy, Nagpur, Maharashtra

Abstract and Figures

A simple, precise and accurate spectrophotometric method has been developed for simultaneous estimation of etoricoxib and paracetamol in combined dosage form using multicomponent mode of analysis. It involves the measurements of absorbance at five selected wavelengths 235 nm, 243 nm, 264 nm, 284 nm and 295 nm using methanol and hydrochloric acid (0.2 N) as a solvent. Linearity was observed in the range of 1-50 μ.g/mL for mixture. The recovery studies confirmed the accuracy of the proposed method. The results were validated as per ICH guidelines.
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ISSN: 0975-8585
July September 2010 RJPBCS Volume 1 Issue 3 Page No. 485
Research Journal of Pharmaceutical, Biological and Chemical
Sciences
Simultaneous Estimation of Etoricoxib and Paracetamol in Combined Tablet
Dosage Form
DR Chaple*, DS Fandi, PD Chaple1
* J. L. Chaturvedi College of Pharmacy, MIDC, Hingna Road, Electronic Zone building, Nagpur-440016
1 Priyadarshani Polytechnic, MIDC, Hingna Road, Nagpur
ABSTRACT
A simple, precise and accurate spectrophotometric method has been developed for simultaneous
estimation of etoricoxib and paracetamol in combined dosage form using multicomponent mode of analysis. It
involves the measurements of absorbance at five selected wavelengths 235 nm, 243 nm, 264 nm, 284 nm and
295 nm using methanol and hydrochloric acid (0.2 N) as a solvent. Linearity was observed in the range of 1-50
µg/mL for mixture. The recovery studies confirmed the accuracy of the proposed method. The results were
validated as per ICH guidelines.
Key words: Etoricoxib, Paracetamol, Multicomponent mode
*Corresponding author
E-mail: d.chaple@rediffmail.com
ISSN: 0975-8585
July September 2010 RJPBCS Volume 1 Issue 3 Page No. 486
INTRODUCTION
Etoricoxib is a new non-steroidal anti-inflammatory drug (NSAID) with selective
COX-2 inhibitory activity. Chemically it is 5-chloro-2-(6-methylpyridin-3-yl)-3-(4-
methylsulfonylphenyl) pyridine. It is commonly used for osteoarthritis, rheumatoid arthritis,
primary dysmenorrhoea, postoperative dental pain and acute gout. This drug is not official
in any pharmacopoeia. Paracetamol is 4-hydroxy acetanilide used as antipyretic agent.
Literature survey revealed that some analytical methods have been used for individual
estimation of etoricoxib like spectrophotometric, HPLC and HPTLC. Paracetamol is official in
IP, BP and USP. There are many reported UV spectrophotometry and HPLC methods for
determination of paracetamol in bulk drugs, formulation and biological fluids. It has been
found that no method is reported for the simultaneous estimation of etoricoxib and
paracetamol in combined dosage form [1-15].
MATERIAL AND METHOD
Materials
The pure drug samples of etoricoxib (99.83%) and Paracetamol (98.37%) were
obtained from Cadila Ltd., Raigad, (M.S), India. and Zim Laboratories, Kalmeshwar India.
Methanol AR grade and hydrochloric acid (0.2 N) were used throughout the experimental
work. Tablets were purchased from local market (Nucoxia-P tablet), containing etoricoxib 60
mg and Paracetamol 500 mg per tablet.
Instruments
All Absorbance measurements were made on Shimadzu model UV 1601 double beam UV-
Visible spectrophotometer with matched quartz cuvettes.
Standard stock solution
Standard stock solutions of etoricoxib (1mg/mL) and Paracetamol (1mg/mL) were
prepared in methanol and further dilutions were carried out in hydrochloric acid (0.2 N) to
get the concentration 2µg/mL and 16.6 µg/mL.
Method
a) Selection of sampling wavelength
Solutions of etoricoxib (2 µg/mL) and Paracetamol (16.6 µg/mL) were scanned under
the range of 400-200 nm. Overlying spectra was obtained. Sampling wavelengths 235 nm,
243 nm, 264 nm, 284 nm and 295 nm were selected on trial and error basis.
ISSN: 0975-8585
July September 2010 RJPBCS Volume 1 Issue 3 Page No. 487
b) Study of Beer lambert’s law
Solution of etoricoxib (1mg/mL) and paracetamol (1mg/mL) were diluted with
hydrochloric acid (0.2 N) to get final concentration in the range of mixed standard as
fallows.
Laboratory Mixture
Drugs
Concentration in µg/mL
1
2
3
4
5
Etoricoxib
1
2
3
4
5
Paracetamol
8.3
16.6
24.8
33.1
41.2
All the mixed standard solutions were scanned over the range of 400-200 nm in the
multicomponent mode, using five sampling wavelengths as selected on trial basis as given
above. An overlain spectrum of the mixed standard solutions was given in Fig. 1. The graph
was plotted as concentration verses absorbance and it was found to be linear for both the
drugs (Fig. 2).
c) Analysis of tablet formulation
Twenty tablets were weighed and finely powdered and finely powdered. An
accurately weighed quantity of powder equivalent to 50 mg of etoricoxib was transferred to
50 mL volumetric flask and dissolved in 25 mL methanol. It was diluted up to the mark with
with methanol. The solution was filtered through whatmann filter paper no.41. The
resulting solution was further diluted with hydrochloric acid (0.2 N) to get concentration
within concentration range of mixed standards. This solution was subjected to analysis in
the multicomponent mode of instrument at selected wavelength. The result of analysis is
shown in Table 1.
d) Validation of method
The proposed method was validated on the basis of parameters namely accuracy,
precision, linearity and range and ruggedness. The accuracy of the method was ascertained
by carrying out recovery studies using standard addition method and found to be
satisfactory. The result of recovery study is shown in Table 1.
TABLE NO.1: ASSAY OF FORMULATIONS AND RECOVERY STUDIES
% label claim**
% recovery**
98.95±1.45
101.68±1.18
98.85±0.584
99.39±0.302
* Nucoxia-P tablet - each tablet contains etoricoxib 60 mg and Paracetamol 500 mg
** indicates mean of five determinations.
ISSN: 0975-8585
July September 2010 RJPBCS Volume 1 Issue 3 Page No. 488
The precision of an analytical method was as SD or RSD. Linearity and range was
carried out in the range of 1-50 µg/mL and absorbance was recorded at selected
wavelength. The linearity of graph is shown in Fig 2. Ruggedness test was carried out under
different conditions by repeating the procedure under different conditions, i.e., on different
days, at different time and by different analysts.
Fig. 1: Overlain Spectrum laboratory mixtures
Fig. 2: Beer Lambert’s law plot
DISCUSSION
The proposed method for estimation of etoricoxib and paracetamol in combined
dosage forms was found to be simple, accurate, economical and rapid. The method was
validated as per the ICH guidelines. The values of SD and RSD are within the prescribed limit
of 2%, showing high precision of method and recovery was close to 100% for both the drugs.
ACKNOWLEDGEMENTS
The authors are thankful to M/S Cadila Ltd., Raigad, and Zim Laboratories,
Kalmeshwar for providing gift sample of drugs.
ISSN: 0975-8585
July September 2010 RJPBCS Volume 1 Issue 3 Page No. 489
REFERENCES
[1] Cochrane DJ, Jarvis B and Keating GM. Drug 2002; 62: 2637.
[2] Singh RM, Kumar Y, Sharma DK, Mathur SC, Singh GN, Ansari TA and Jamil S. Indian
Drugs 2005; 42: 535.
[3] Suhagia BN, Patel HM, Shah SA, Rathod IS and Marolia BP. Indian J Pharm Sci 2005;
67: 634-637.
[4] Chaple DR and Bhusari KP. Research J Pharm and Tech 2009; 2: 597-598.
[5] Ramakrishna NVS, Vishwottam KN, Wishu S and Koteshwara M. J Chromat B 2005;
816: 215.
[6] Bräutigam L, Jens U. Nefflen JU and Geisslinger G. J Chromat B 2003; 788: 309.
[7] Ansari TA, Jamil S, Singh RM, Mathur SC, Shivraj and Singh GN. Indian Drugs 2005;
42: 56.
[8] Mandal U, Rajan DS, Bose A, Gowda KV, Ghosh A and Pal T. K. Indian J Pharm Sci
2006; 68: 485-489.
[9] Shah NJ, Shah SJ, Patel DM and Patel NM. Indian J Pharm Sci 2006; 68: 788-789.
[10] Indian Pharmocopoeia, Vol 1, Government of India, The Controller of Publications,
Delhi, 1985, 359.
[11] British pharmacopoeia, General Medical Council, 1998, 743.
[12] United States of Pharmacopoeia, US Pharmacopoeia Convention, 2003; 23:16.
[13] Nagaraja P, Murthy KC and Rangappa KS. J Biopharma Biomed Anal 1998;17:501.
[14] Milch G and Szabo E. J Pharma Biomed Anal 1991;9:1107.
[15] Martin A, gaecia A and Barbas C. J Biopharm Anal 2002; 29:701.
[16] Nagaralli BS, Seetharmappa J, Gowda BG and Merwanki MB. J Chromatgr B Analyst
2003; 798:49.
... 18 The identification of these drugs in pharmaceutical dose forms, either alone or in combination with other pharmaceuticals, has been documented using spectrophotometric methods, HPLC methods stabilityindicating methods, and plasma extraction methods, according to a literature review with the combination of the above-mentioned medicines, a few UV, HPLC methods. [19][20][21][22] There are options with smaller linearity ranges and/or longer retention times. The author attempted to design and validate a low-cost and precise RP-HPLC estimation method for Etoricoxib and Paracetamol in formulated dosage forms. ...
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An RP-HPLC technique was used to produce a cost-effective simultaneous quantification of Etoricoxib and Paracetamol in combined pharmaceutical tablet dosage forms. The approach was validated for Etoricoxib and Paracetamol using ICH recommendations over a range of 20-120ppm and 20-200ppm, respectively. At a temperature of 250C±0.50C, an analytical column PURITAS™ EXIMIUS C18, 250mmx4.6mm, 5 microns was utilized. At a flow rate of 1.0 ml/min, the mobile phase was acetonitrile and 0.1 percent acetic acid in water in a 70:30V/V ratio. The elution was examined using a PDA detector with a detection wavelength of 235nm. The retention times for Etoricoxib and paracetamol are 4.2 and 2.1 minutes, respectively. The percentage recoveries for Etoricoxib and paracetamol were 98.28% and 102.1%, respectively. The RSD values are not greater than 2%.
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  • D J Cochrane
  • Jarvis B Keating
Cochrane DJ, Jarvis B and Keating GM. Drug 2002; 62: 2637.
  • Rm Singh
  • Y Kumar
  • Dk Sharma
  • Sc Mathur
  • Gn Singh
  • Ta Ansari
  • S Jamil
Singh RM, Kumar Y, Sharma DK, Mathur SC, Singh GN, Ansari TA and Jamil S. Indian Drugs 2005; 42: 535. [3]
  • B N Suhagia
  • H M Patel
  • S A Shah
  • Rathod Is
  • B P Marolia
Suhagia BN, Patel HM, Shah SA, Rathod IS and Marolia BP. Indian J Pharm Sci 2005; 67: 634-637.
  • Dr Chaple
  • Kp Bhusari
  • Nvs Ramakrishna
  • Kn Vishwottam
  • S Wishu
  • M Koteshwara
Chaple DR and Bhusari KP. Research J Pharm and Tech 2009; 2: 597-598. [5] Ramakrishna NVS, Vishwottam KN, Wishu S and Koteshwara M. J Chromat B 2005; 816: 215. [6]
  • L Bräutigam
  • Jens U Nefflen
  • G Geisslinger
Bräutigam L, Jens U. Nefflen JU and Geisslinger G. J Chromat B 2003; 788: 309.