Asian J. Research Chem. 2(2): April.

-June, 2009 ,

ISSN 0974-4169 RESEARCH ARTICLE

www.ajrconline.org

Spectrophotometric Method for Simultaneous Estimation of Paracetamol and Domperidone in Tablet Formulation
Kanak Manjari Institute of Pharmaceutical Sciences, Rourkela, Orissa *Corresponding Author E-mail: kapil752003@yahoo.com

Kalra Kapil*, Naik S, Jarmal Garima and Mishra N

ABSTRACT

The development of Vireodt's method for simultaneous estimation of paracetamol and domperidone involves absorbance measurement at 250 nm and 285 nm corresponding to the respective absorption maxima. Both the drugs obey Beer Lambert's law in the range of 5-30 g/ml for paracetamol and 0.8-5 g/ml for domperidone. The tablet formulation (Grenil, KAPL) was evaluated for the percent content of both the drugs at the selected wavelengths. The method developed was validated to determine its accuracy, precision, specificity and ruggedness. The recovery study was carried out by standard addition method. The average percent recovery was found to be 99.450.47 for paracetamol and 100.670.18 for domperidone KEY WORDS: Paracetamol, Domperidone, Spectrophotometric estimation. Domperidone (DMP) is chemically 5-chloro-1-[1-[3-(2oxo-2,3-dihydro-1 H -benzimidazol-1-yl) propyl]piperidin-4-yl]-1,3-dihydro-2 H -benzimidazol-2-one used as antiemetic drug. Paracetamol (PAR), chemically 4-hydroxy acetanilide, is a centrally and peripherally acting non-opioid analgesic and antipyretic. A combination of these drugs, DMP (20 mg), and PAR (500 mg) is available as tablets for clinical practice. Their combination is used for the treatment of migraine. A Survey of literature reveals that various methods like HPLC 1-3, NMR, U.V4-12 are available for Individual determination of domperidone, paracetamol. However there is no spectrometric method for the simultaneous determination of the paracetamol and domperidone. An attempt was made to develop accurate, precise, reproducible and economical vireodt's method for simultaneous estimation of both these drugs in combined dosage form. The instrument used in the present study was double beam UV/Visible spectrophotometer with 10 mm matched quartz cell. (Model UV-2401, Shimadzu, Japan) The methanol solution of paracetamol (PAR) and domperidone (DOM) was prepared to get final concentration of 1 mg/ml. (PAR- Stock solution A, DOM- Stock solution B) Received on 10.02.2009 Accepted on 22.05.2009 Modified on 25.04.2009 AJRC All right reserved

INTRODUCTION:

The resultant solution was further diluted with distilled water to get final concentration of 10 g/ml of PAR and DOM (standard solution). Both the drugs were scanned in the scanning range of 200-400 nm. The scanned spectra were then analyzed for the selection of wavelengths ( max) for both the drugs. Dilutions were made to standard solutions of PAR and DOM individually, and mixture of PAR and DOM was scanned for the linearity curve response on the selected wavelengths. For the estimation of pure drugs by the proposed method, Solutions of 1 g/ml of domperidone and 25 g/ml of paracetamol and a mixture containing 1 g/ml nad 25 g/ml of both the drugs were selected for determination of absorbance values. The contents were calculated using the following equations. C x =(A 2 ay 1 A 1 ay 2 )/(ax 2 ay 1 -ax 1 ay 2 ), C Y =(A 1 ax 2 -A 2 ax 1 )/(ax 2 ay 1 -ax 1 ay 2 ), where C x and Cy are the concentrations of domperidone and paracetamol respectively, ax 1 and ax 2 are the absorptivity values of domperidone at 285 nm and at 250 nm respectively, ay1 and ay 2 are the absorptivity values of paracetamol at 285 nm and at 250 nm respectively and A 1 and A 2 are the absorbances of the diluted sample at 285 nm and at 250 nm respectively. For the estimation of drugs in the marketed preparations, 20 tablets containing 20 mg domperidone and 500 mg paracetamol ( Grenil) were weighed and finely powdered. A quantity of powder equivalent to 10 mg domperidone and 250 mg paracetamol was accurately weighed and transferred to a 50 ml volumetric flask, dissolved in methanol and the solution was filtered through Whatman filter paper no. 1

MATERIALS AND METHODS:

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Table 1: AMOUNT AND % CLAIM CALCULATED FOR BOTH THE DRUGS Label Claimed (mg/tab) Amount Claimed (mg/tab) % of label Claimed Drug GRENIL Paracetamol 500 499.85 99.97 Domperidone 20 19.77 98.85

Asian J. Research Chem. 2(2): April.-June, 2009 ,

% Recovery 99.45 100.67

Table 2 : QUANTITATIVE PARAMETERS / OPTICAL CHARACTERISTICS OF THE PROPOSED METHOD Parameters Domperidone Paracetamol Beers Law Limit ( g/ml) 0.8 5 5 30 Sandells Senstivity ( g/cm2) 0.023 0.055 Limit of detection ( g/ml) 0.2 0.2 Limit of quantification ( g/ml) 1.0 1.0 Regression equation (Y*) Slope (B) 0.0229 0.0546 Intercept (A) 0.001 0.002 Correlation coefficient (r) 1.0 1.0 Molar absorptivity (1/mol/cm) 9984 8375.2 Y = A +Bx , where x is the concentration of the analyte and y is the absorbance value Table 3 : % LABELLED CLAIM OF PARACETAMOL AND DOMPERIDONE AFTER STABILITY STUDIES Stress Condition/ Duration State Normal Thermal/80C/ 48h/Solid Thermal/80C/ 48h/Solution Acidic Alkaline Oxidation % Labelled Claim of Domperidone (285nm) 99.86 97.89 97.99 96.51 96.67 97.87 % Labelled Claim of Paracetamol (250nm) 98.89 98.56 99.23 98.72 98.36 98.35

and the volume was made up to the mark with the same solvent. Aliquots of this tablet solution were diluted to get the concentrations ~ 1 g/ml of domperidone and ~ 25 g/ml of paracetamol. The sample solutions were scanned over the range of 190-400 nm. Absorbance of the sample solutions at 285 nm and 250 nm was measured and from the absorbance values, the concentration of drugs in the sample solution was determined by using vierodt's formula. The amount and % Claim calculated for both the drugs are shown in [Table 1]. The accuracy of the proposed method was ascertained by carrying out recovery studies by standard addition method. The recovery study was performed to determine if there was any positive or negative interference from excipients present in formulation. The method was ascertained on the basis of recovery study by standard addition method applied to reanalyzed sample. Precision of an analytical method is expressed as SD or RSD of a series of measurements. It was ascertained by replicate estimation of drug by the proposed method. The specificity is the ability to assess unequivocally the analyte for the presence of interesting components that may be expected to be present, such as impurities, degradation product and matrix components. The sample solution was prepared to get a mixed standard solution and allowed to be stored for 24 h under the following different conditions, like room temperature (normal), at

50 after addition of 1.0 ml of 0.1 N of hydrochloric acid (acid), at 50 after addition of 1.0 ml of 0.1 N of sodium hydroxide (alkali), at 50 after addition of 3% of hydrogen peroxide (oxidation), After 24 h, the contents of the flask were made to undergo the same treatment as previously described. Test for ruggedness was carried out under different conditions, i.e., different days and by different analysts. An attempt was made to develop a fast, sensitive, precise, reproducible and economical analytical method for simultaneous estimation of PAR and DOM in their combined dosage form. DOM was standardized by official method reported in British Pharmacopoeia, and the purity of the sample was found to be 99.40%. The purity of PAR was standardized by official method reported in Indian Pharmacopoeia, and the purity of the sample was found to be 99.28%.The diluted solution was scanned to obtain spectrum for both PAR and DOM. The max of both the drugs were determined from the obtained spectra - 250 nm for PAR and 285 nm for DOM. PAR obeys Beer Lambert's law in the range of 5-30 g/ml and DOM in the range of 0.8 - 5 g/ml. The absorption additivity study was also carried out to see whether the drugs in mixture followed additivity study or not. It was observed that both the drugs were following absorption additivity study with respect to theoretical and practically obtained values. E (1%, 1 cm)

RESULTS AND DISCUSSION:

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values were also calculated for both the drugs. For PAR, E (1%, 1 cm) was found to be 5511.61, 478.81.10; and for DOM, it was 169.88, 230.664.34 at the respective wavelengths of 250 nm and 285 nm. The method was validated according to ICH guidelines. The accuracy of the method was evaluated by percentage recovery (by standard addition method) of both the drugs. The average percent recovery was found to be 99.450.47 and 100.670.18. The result of the method lies within the prescribed limit of 98-102%, showing that the method is free from interference from excipients. The next parameter considered was precision. The replicate estimation of both PAR and DOM in the same batch of tablets was analyzed by the proposed method and has yielded quite concurrent results, indicating reliability of the method. The values of SD or RSD and coefficient of correlation are within the prescribed limit of 2%, showing high precision of the method. The optical characteristics such as Beer's law limits, detection limit, molar absorptivities and Sandell's sensitivities are presented in [Table 2]. Other parameters studied were specificity and ruggedness to study degradation and stability of the method. In specificity study, the sample was exposed to different stress conditions like acid, alkali, oxide, heat and UV/visible light, showing degradation of the drugs under oxide and acidic conditions, but this method is incapable of finding exact degradation of drugs. The last parameter studied was ruggedness, which shows that the result of estimation for the proposed method was reproducible under different conditions, like different days and by different analysts, as shown in [Table 3]. The aboveevaluated parameters in the proposed method revealed that the experimental study signifies simple, accurate, fast, precise and reproducible Vireodt's method for simultaneous estimation of PAR and DOM in their combined dosage form and can be used for routine analysis of both the drugs in commercially available marketed formulations.

Asian J. Research Chem. 2(2): April.-June, 2009 ,

The authors are thankful to Alpha Remedies Limited, Hingna, Nagpur and Vamsi Labs Ltd, Solapur, Maharashtra for providing gift samples of Paracetamol and domperidone.
Kanumula, G. V., Raman B., Indian Drugs , 2000;37,:375 Novakovic, J., Journal of Chromatography. A, 1999;846 :193 3. Xia, S., Tan, H., Tang, W. and Weihong, Zhongguo Yiyuan Yaoxulzazhi , 1999;19 :145. 4. Pharmacopoeia of India, 3rd Edn.Controller of Publications, Govt. of India, New Delhi, 1996;1 :554. 5. British Pharmacopoeia, Her Majesty Stationery Office, London, 1998;2: 743. 6. United States of Pharmacopoeia 23 and NF18, US Pharmacopoeial Convention, Rockville, MD, 2003 :16. 7. Mashru, R.C. and Banerjee, S.K., Eastern Pharmacist , 1998;41:141. 8. Sodhi, R.A., Chawla, J.L. and Sane, R.T. Indian Drugs , 1996,;33:280. 9. Mao, B., Abrahim, A.G., Ellison, D.K. and Wyvratt, J., Journal of Pharmaceutcial Biomedical Analysis., 2002; 28: 1101. 10. Indian Pharmacopoeia, Govt. of India, Ministry of Health and Family Welfare, Delhi. Publication by Controller of Publication; 1996; 2: 484, 554 11. British Pharmacopoeia, 1993, Vol. 1, International ed. Published on the Recommendation of the Medicines Commissions Pursuant to Medicines Act; 1968, 1993. 429,483 12. Karthik A. et al. Simultaneous estimation of paracetamol and domperidone in tablets by reverse phase HPLC method, Indian J Pharm Sci. 2007; 69:142:144 1. 2.

ACKNOWLEDGEMENTS:

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