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column were calculated by statistical analysis to determine system suitability of the method. The number of theoretical plates per column was 22961 and the symmetry factor was 1.01. The validated method was applied for determination of residual solvents in certain film-coated marketed antibiotic formulation of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin. Twenty tablets each containing 500 mg, 400 mg, 400 mg, and 200 mg of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin, respectively were accurately weighed separately. The tablets were crushed in a separate glass mortar into a fine powder, transferred into a stoppered conical flask, and extracted with 100 ml portion of dimethyl sulfoxide. The extract was filtered with Whatman filter paper No. 1 into a clean, dry 100 ml volumetric flask to get sample stock solution. A volume of 2 ml of the sample stock solution was diluted to 10 ml using dimethyl sulfoxide. From the filtered solution, 5 µl was injected into the gas chromatograph. Methylene chloride peak was detected at 5.4 min in the chromatograms of sample ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin. Based on the peak areas recorded in the chromatograms, the amounts of organic volatile impurity present in the samples were calculated.
Methylene chloride was found to be in the concentration range of 0.001 to 0.003 mg per tablet, which was well within the permissible limit of 600 ppm as required by the specification of ICH. The amounts of residual solvents found in the marketed formulations have been presented in Table 1.
REFERENCES 1. 2.
Rastogi, S.C., Chromatographia., 1993, 37, 211. Kevin, J.M. and Thomas, W.B., J. Chrom. Biomed. Appl.,1996, 686, 85. 3. Hymer, B.C., J. Chrom., 1988, 438, 103. 4. Hong, L. and Altorfer, H., Chromatograpia., 2001, 53, 76. 5. Russo, M.V., Chromatographia., 1994, 39, 645. 6. Muligan, K.J. and Mc Cauley, H., J. Chrom. Sci., 1995, 33, 49. 7. Smith, I.D. and Water, D.G., Analyst., 1991, 116, 1327. 8. Capitani, F., Nocilli, F. and Porretta, G.C., Farmaco., 1988, 43, 189. 9. Witschi, C. and Doelker, E., Eur. J. Pharm. Biopharm., 1997, 43, 215. 10. Kumar, N. and Egoville, J.C., J. Chrom. A., 1999, 859, 113.
Accepted 29 May 2006 Revised 8 July 2005 Received 24 January 2005 Indian J. Pharm. Sci., 2006, 68 (3): 368-370
Simultaneous Spectrophotometric Estimation of Valdecoxib and P aracetamol in T ablet FFormulations ormulations Paracetamol Tablet N. ADITYA, R. K. ARORA, AND MEENA TIWARI* Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23, Park Road, Indore-452 003, India.
A simple, accurate, economical, and reproducible method for simultaneous estimation of valdecoxib and paracetamol in two-component tablet formulation has been developed. The method of analysis is derivative spectroscopy to eliminate spectral interference by measuring absorbances at two wavelengths 284 nm and 301 nm for valdecoxib and paracetamol, respectively. The results obtained in triplicate were validated statistically and by recovery studies.
Valdecoxib1 (VAL), 4-(5-methyl-3-phenyl-4-isooxazoyl) benzene sulphonamide) has analgesic and antiinflammatory activity. Extensive literature survey revealed *For correspondence E-mail:
[email protected] 370
its estimation by high performance liquid chromatography method 2-3 only. Paracetamol 4 (PCM), 4-hydoxy acetanilide, has analgesic and antipyretic activity. Reported methods of analysis involve spectrophotometric methods5-7, chromatographic methods8-10, titrimetric11 and electrochemical methods 12 . The analysis of this
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combination is of prime importance since valdecoxib is present in a small quantity relative to paracetamol. Therefore, development of simultaneous spectrophotometric method for estimation of both drugs in tablet formulation is a worthwhile objective. The drug combination of PCM and VAL is indicated for symptomatic relief of rheumatoid arthritis and in the treatment of dysmenorrhoea. The present work is a simple, rapid, and economical method for the simultaneous estimation of VAL and PCM in two-component tablet formulation. A Shimadzu UV spectrophotometer 160A model with spectral bandwidth of 3 nm and wavelength accuracy of ±0.5 nm was used. Ten mm matched quartz cells were employed for this work. Methanol (AR grade) was used as solvent. VAL and PCM were obtained as gift samples from Torrent Research Center, Gandhinagar; and Ranbaxy Laboratories, Dewas, respectively. The commercial formulations of VAL and PCM are available in ratio of 1:25 {Valeron Plus (20/500 mg) [Formulation A]} and 1:32.5 {Validay Plus (10/325 mg) [Formulation B]}, respectively as tablets.
weighed in case of Formulation A/B, respectively and was dissolved in about 25 ml of methanol, stirred for 30 min, and final volume was made up to 50 ml with methanol. The solution was filtered through Whatman filter paper No. 41, and the first few ml were rejected. 19.2/25.2 ml of standard solution of VAL (25 µg/ml) was added to 1 ml of filtered solution in case of Formulation A/B, respectively. To make the solution of equal concentrations for both the drugs, final volume was made up to the mark (50 ml) with methanol. The zero-order absorption spectra were derivatized, and derivative spectra from first to fourth order were recorded. Considering all these derivative spectra of VAL and PCM, the second-order derivative spectrum for VAL and first-order derivative spectrum for PCM were selected (fig. 2 and 3, respectively). Five mixed standards of 2.5, 5.0, 7.5, 10.0, and 12.5 µg/ml concentrations of each drug were prepared from stock solutions of the drugs. All the mixed standards were scanned over the range of 400-200 nm and derivatized to measure substantial absorbance at 284 nm for VAL and
Standard stock solutions of VAL and PCM of 100 µg/ml each were prepared in methanol. Each was suitably diluted to different concentrations and linearity was studied. Linear relationships were observed in the range of 0-25 µg/ml for both VAL and PCM. Standard solutions of 10 mg/ml from pure samples of VAL and PCM were prepared separately. These solutions were scanned over the range of 400-200 nm. The overlain zero-order spectra of VAL and PCM are shown in fig. 1. Spectra indicate the absorption maxima of VAL and PCM at 239 nm and 248 nm, respectively. Tablet powder equivalent to 25/32.5 mg of PCM was
Fig. 2: Overlain first-order derivative spectrum of valdecoxib (val) and paracetamol (pcm) in methanol.
Fig. 1: Overlain spectra of valdecoxib (val) and paracetamol (pcm) in methanol.
Fig. 3: Overlain second-order derivative spectrum of valdecoxib (val) and paracetamol (pcm) in methanol.
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TABLE 1: STATISTICAL ANALYSIS OF RESULTS FOR VALDECOXIB AND PARACETAMOL IN TABLET FORMULATIONS Brand name
Name of manufacturer
Strength
Amount found (mg/tablet)
% Found
Standard deviation
Coefficient of variance
Valeron plus
CFL Pharmaceuticals Ltd.
val 20 mg/Tablet pcm 500 mg/Tablet val 10 mg/Tablet pcm 325 mg/Tablet
20.04
100.2
0.2115
2.1104
494.01
98.8
0.1281
1.2968
10.10
101.0
0.1221
0.9304
321.74
99.0
0.0739
0.5747
Validay plus
Mankind Pharmaceuticals Ltd.
pcm: paracetamol, val: valdecoxib
TABLE 2: RESULTS OF RECOVERY STUDIES FOR VALDECOXIB AND PARACETAMOL IN TABLET FORMULATIONS Brand name
Valeron plus
Validay plus
Name of manufacturer
Strength
CFL Pharmaceuticals Ltd.
val 20 mg/Tablet pcm 500 mg/Tablet Mankind Pharmaceuticals Ltd. val 10 mg/Tablet pcm 325 mg/Tablet
Concentration of added drug in µ g/ml) preanalysed solution (µ
% Recovery
val
pcm
val
pcm
1.0 2.0 3.0
1.0 2.0 3.0
98.8 99.4 101.5
102.8 101.6 99.7
1.3 2.6 3.9
1.3 2.6 3.9
99.7 100.9 99.4
99.6 99.5 100.2
pcm: paracetamol, val: valdecoxib
301 nm for PCM, respectively. Then, working Eqns. 1 and 2 for both the drugs were derived. For valdecoxib: CVAL = AVAL 211.51+(-0.1304)…1 and for paracetamol: CPCM = APCM128.13+0.1424…2, where CVAL and CPCM are the concentrations of VAL and PCM, respectively, and AVAL and APCM are the absorbances of VAL (284 nm) and PCM (301 nm), respectively. Sample solutions of appropriate dilution were prepared and scanned. Absorbances of these solutions at 284 nm and 301 nm were noted after derivatization in first and second order. The concentrations of both components were computed using Eqns. 1 and 2. Analysis data of tablet formulations are reported in Table 1. In order to ascertain the reproducibility of the proposed method, recovery studies were carried out by adding known amount of drugs to the pre-analyzed sample solution. Results of recovery studies were found to be satisfactory and are reported in Table 2. Valdecoxib and paracetamol obeyed Beer’s law in the concentration range of 0-25 µg/ml. In formulation A, the percentage composition of valdecoxib was found to be 100.2% (Standard deviation ±0.2115) and that of paracetamol was found to be 98.8% (Standard deviation 372
±0.1281). In formulation B, the percentage composition of valdecoxib was found to be 101.0% (Standard deviation ±0.1221) and that of paracetamol was found to be 99.0% (Standard deviation ±0.0739). Simultaneous estimation of valdecoxib and paracetamol by derivative spectrophotometry was found to be simple and accurate. The value of standard deviation and coefficient of variance was significantly low and recovery was close to 100%, indicating the reproducibility of the method. The method is used to eliminate the spectral interference from one of the two drugs while estimating the other drug by selecting the zero-order crossing point on the derivative spectra of each drug at the selected wavelengths. It is concluded that the proposed method is simple, accurate, and can be successfully employed for simultaneous estimation of valdecoxib and paracetamol in two-component tablet formulations.
ACKNOWLEDGEMENTS The authors thank the Torrent Research Center, Gandhinagar; and Ranbaxy Laboratories Limited, Dewas (MP), for providing gift samples of the drugs. The authors
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are also thankful to Mr. A. K. Gupta, Research Scholar, CSIR, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore, for his invaluable help to carry out this work.
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Chavez, M.L. and Dekorte, C.J., Clin. Ther. , 2003, 25, 817.
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Ellock, C.T.H. and Fogg, A.G., Analyst, 1975, 100,16. Rana, N.G. and Chouhan, M.V., Indian Drugs, 1977, 14,184. Srewart, J.T., Honigberg, I.L. and Coldern, J.W., J. Pharm. Sci.,
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Accepted 30 May 2006
Revised 8 July 2005
Received 24 February 2005
Indian J. Pharm. Sci., 2006, 68 (3): 370-373
Visible Spectrophotometric Determination of Valdecoxib in T ablet Dosage FForms orms Tablet A. SUGANTHI*, H. B. SIVAKUMAR, S. C. VIJAYAKUMAR, P. RAVIMATHI AND T. K. RAVI Department of Pharmaceutical Analysis, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore-641 044, India.
A simple, accurate, rapid, and sensitive visible spectrophotometric method has been developed for the determination of valdecoxib in pure and pharmaceutical dosage forms. The method is based on the reaction of valdecoxib with potassium permanganate to form a bluish green coloured chromogen with an absorption maximum at 610 nm. Beer’s law was obeyed in the range of 5-25 µg/ml. The proposed method has been successfully applied to the analysis of the bulk drug and its dosage forms
Valdecoxib is a nonsteroidal antiinflammatory drug that exhibits antiinflammatory, analgesic, and antipyretic properties. Chemically, it is 4–(5-methyl–3-phenylisoxazolyl) benzene sulphonamide1. It is a novel COX-2 inhibitor with a lower incidence of ulcer complication. It has been found to be an effective analgesic in postoperative pain. Literature survey revealed that a HPLC method has been reported for the bioequivalence of valdecoxib in plasma2-4. However, there is no method reported for estimation of valdecoxib in formulation. The *For correspondence E-mail:
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present paper aims to report a simple visible spectrophotometric method for estimation of valdecoxib in tablets. Valus and Valz, containing 10 mg/tab, which are manufactured and marketed by Glenmark Pharmaceuticals Ltd. and Torrent Pharmaceuticals Ltd. were estimated. Valdecoxib was obtained as a gift sample from Glenmark Pharmaceuticals Ltd., Mumbai. A Jasco V-530 UV/Vis spectrometer with 1 cm matched quartz cells was used for all absorbance measurements. All chemicals used were of analytical grade and procured from SD Fine Chemicals, Mumbai.
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