Spectrophotometric Method for Simultaneous Estimation of ...

Asian J. Research Chem. 2(2): April.-June, 2009,ISSN 0974-4169www.ajrconline.orgRESEARCH ARTICLESpectrophotometric Method for Simultaneous Estimation of Paracetamol andDomperidone in Tablet FormulationKalra Kapil*, Naik S, Jarmal Garima and Mishra NKanak Manjari Institute of Pharmaceutical Sciences, Rourkela, Orissa*Corresponding Author E-mail: kapil752003@yahoo.comABSTRACTThe development of Vireodt's method for simultaneous estimation of paracetamol and domperidone involvesabsorbance measurement at 250 nm and 285 nm corresponding to the respective absorption maxima. Both the drugsobey Beer Lambert's law in the range of 5-30 µg/ml for paracetamol and 0.8-5 µg/ml for domperidone. The tabletformulation (Grenil, KAPL) was evaluated for the percent content of both the drugs at the selected wavelengths. Themethod developed was validated to determine its accuracy, precision, specificity and ruggedness. The recovery studywas carried out by standard addition method. The average percent recovery was found to be 99.45±0.47 forparacetamol and 100.67±0.18 for domperidoneKEY WORDS: Paracetamol, Domperidone, Spectrophotometric estimation.INTRODUCTION:Domperidone (DMP) is chemically 5-chloro-1-[1-[3-(2-oxo-2,3-dihydro-1 H -benzimidazol-1-yl) propyl]-piperidin-4-yl]-1,3-dihydro-2 H -benzimidazol-2-oneused as antiemetic drug. Paracetamol (PAR), chemically4-hydroxy acetanilide, is a centrally and peripherallyacting non-opioid analgesic and antipyretic. Acombination 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 likeHPLC 1-3 , NMR, U.V 4-12 are available for Individualdetermination of domperidone, paracetamol. Howeverthere is no spectrometric method for the simultaneousdetermination of the paracetamol and domperidone. Anattempt was made to develop accurate, precise,reproducible and economical vireodt's method forsimultaneous estimation of both these drugs in combineddosage form. The instrument used in the present studywas double beam UV/Visible spectrophotometer with 10mm matched quartz cell. (Model UV-2401, Shimadzu,Japan)MATERIALS AND METHODS:The methanol solution of paracetamol (PAR) anddomperidone (DOM) was prepared to get finalconcentration of 1 mg/ml. (PAR- Stock solution A,DOM- Stock solution B)Received on 10.02.2009 Modified on 25.04.2009Accepted on 22.05.2009 © AJRC All right reservedAsian J. Research Chem. 2(2): April.-June, 2009 page 112-114The resultant solution was further diluted with distilledwater to get final concentration of 10 µg/ml of PAR andDOM (standard solution). Both the drugs were scannedin the scanning range of 200-400 nm. The scannedspectra were then analyzed for the selection ofwavelengths ( max) for both the drugs.Dilutions were made to standard solutions of PAR andDOM individually, and mixture of PAR and DOM wasscanned for the linearity curve response on the selectedwavelengths. For the estimation of pure drugs by theproposed method, Solutions of 1 µg/ml of domperidoneand 25 µg/ml of paracetamol and a mixture containing 1µg/ml nad 25 µg/ml of both the drugs were selected fordetermination of absorbance values. The contents werecalculated 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 theconcentrations of domperidone and paracetamolrespectively, ax 1 and ax 2 are the absorptivity values ofdomperidone at 285 nm and at 250 nm respectively, ay 1and ay 2 are the absorptivity values of paracetamol at 285nm and at 250 nm respectively and A 1 and A 2 are theabsorbances of the diluted sample at 285 nm and at 250nm respectively. For the estimation of drugs in themarketed preparations, 20 tablets containing 20 mgdomperidone and 500 mg paracetamol ( Grenil) wereweighed and finely powdered. A quantity of powderequivalent to 10 mg domperidone and 250 mgparacetamol was accurately weighed and transferred to a50 ml volumetric flask, dissolved in methanol and thesolution was filtered through Whatman filter paper no. 1112

Asian J. Research Chem. 2(2): April.-June, 2009,Table 1: AMOUNT AND % CLAIM CALCULATED FOR BOTH THE DRUGSLabel Claimed (mg/tab) Amount Claimed (mg/tab) % of label Claimed % RecoveryDrugGRENILParacetamol 500499.8599.9799.45Domperidone 2019.7798.85100.67Table 2 : QUANTITATIVE PARAMETERS / OPTICAL CHARACTERISTICS OF THE PROPOSED METHODParameters Domperidone ParacetamolBeer’s Law Limit ( µg/ml)Sandell’s Senstivity ( µg/cm 2 )Limit of detection ( µg/ml)Limit of quantification ( µg/ml)Regression equation (Y*)Slope (B)Intercept (A)Correlation coefficient (r)Molar absorptivity (1/mol/cm)0.8 – 50.0230.21.00.02290.0011.099845 – 300.0550.21.00.05460.0021.08375.2Y = A +Bx , where x is the concentration of the analyte and y is the absorbance valueTable 3 : % LABELLED CLAIM OF PARACETAMOL AND DOMPERIDONE AFTER STABILITY STUDIESStress Condition/ DurationStateNormalThermal/80°C/48h/SolidThermal/80°C/48h/SolutionAcidicAlkalineOxidation% Labelled Claim of Domperidone (285nm) % Labelled Claim of Paracetamol(250nm)99.8698.8997.8998.5697.9996.5196.6797.8799.2398.7298.3698.35and the volume was made up to the mark with the samesolvent. Aliquots of this tablet solution were diluted toget the concentrations ~ 1 µg/ml of domperidone and ~25 µg/ml of paracetamol. The sample solutions werescanned over the range of 190-400 nm. Absorbance ofthe sample solutions at 285 nm and 250 nm wasmeasured and from the absorbance values, theconcentration of drugs in the sample solution wasdetermined 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 ascertainedby carrying out recovery studies by standard additionmethod. The recovery study was performed to determineif there was any positive or negative interference fromexcipients present in formulation. The method wasascertained on the basis of recovery study by standardaddition method applied to reanalyzed sample. Precisionof an analytical method is expressed as SD or RSD of aseries of measurements. It was ascertained by replicateestimation of drug by the proposed method. Thespecificity is the ability to assess unequivocally theanalyte for the presence of interesting components thatmay be expected to be present, such as impurities,degradation product and matrix components. The samplesolution was prepared to get a mixed standard solutionand allowed to be stored for 24 h under the followingdifferent conditions, like room temperature (normal), at50º after addition of 1.0 ml of 0.1 N of hydrochloric acid(acid), at 50º after addition of 1.0 ml of 0.1 N of sodiumhydroxide (alkali), at 50° after addition of 3% ofhydrogen peroxide (oxidation), After 24 h, the contentsof the flask were made to undergo the same treatment aspreviously described. Test for ruggedness was carriedout under different conditions, i.e., different days and bydifferent analysts.RESULTS AND DISCUSSION:An attempt was made to develop a fast, sensitive,precise, reproducible and economical analytical methodfor simultaneous estimation of PAR and DOM in theircombined dosage form. DOM was standardized byofficial method reported in British Pharmacopoeia, andthe purity of the sample was found to be 99.40%. Thepurity of PAR was standardized by official methodreported in Indian Pharmacopoeia, and the purity of thesample was found to be 99.28%.The diluted solutionwas scanned to obtain spectrum for both PAR andDOM. The max of both the drugs were determinedfrom the obtained spectra - 250 nm for PAR and 285 nmfor DOM. PAR obeys Beer Lambert's law in the rangeof 5-30 µg/ml and DOM in the range of 0.8 - 5 µg/ml.The absorption additivity study was also carried out tosee whether the drugs in mixture followed additivitystudy or not. It was observed that both the drugs werefollowing absorption additivity study with respect totheoretical and practically obtained values. E (1%, 1 cm)113

values were also calculated for both the drugs. For PAR,E (1%, 1 cm) was found to be 551±1.61, 478.8±1.10;and for DOM, it was 169.88, 230.66±4.34 at therespective wavelengths of 250 nm and 285 nm. Themethod was validated according to ICH guidelines. Theaccuracy of the method was evaluated by percentagerecovery (by standard addition method) of both thedrugs. The average percent recovery was found to be99.45±0.47 and 100.67±0.18. The result of the methodlies within the prescribed limit of 98-102%, showing thatthe method is free from interference from excipients.The next parameter considered was precision. Thereplicate estimation of both PAR and DOM in the samebatch of tablets was analyzed by the proposed methodand has yielded quite concurrent results, indicatingreliability of the method. The values of SD or RSD andcoefficient of correlation are within the prescribed limitof 2%, showing high precision of the method. Theoptical characteristics such as Beer's law limits,detection limit, molar absorptivities and Sandell'ssensitivities are presented in [Table 2]. Other parametersstudied were specificity and ruggedness to studydegradation and stability of the method. In specificitystudy, the sample was exposed to different stressconditions like acid, alkali, oxide, heat and UV/visiblelight, showing degradation of the drugs under oxide andacidic conditions, but this method is incapable of findingexact degradation of drugs. The last parameter studiedwas ruggedness, which shows that the result ofestimation for the proposed method was reproducibleunder different conditions, like different days and bydifferent analysts, as shown in [Table 3]. The aboveevaluatedparameters in the proposed method revealedthat the experimental study signifies simple, accurate,fast, precise and reproducible Vireodt's method forsimultaneous estimation of PAR and DOM in theircombined dosage form and can be used for routineanalysis of both the drugs in commercially availablemarketed formulations.Asian J. Research Chem. 2(2): April.-June, 2009,ACKNOWLEDGEMENTS:The authors are thankful to Alpha Remedies Limited,Hingna, Nagpur and Vamsi Labs Ltd, Solapur,Maharashtra for providing gift samples of Paracetamoland domperidone.REFERENCES:1. Kanumula, G. V., Raman B., Indian Drugs , 2000;37,:3752. Novakovic, J., Journal of Chromatography. A, 1999;846:1933. Xia, S., Tan, H., Tang, W. and Weihong, ZhongguoYiyuan Yaoxulzazhi , 1999;19 :145.4. Pharmacopoeia of India, 3rd Edn.Controller ofPublications, 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, USPharmacopoeial 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 Healthand Family Welfare, Delhi. Publication by Controller ofPublication; 1996; 2: 484, 55411. British Pharmacopoeia, 1993, Vol. 1, International ed.Published on the Recommendation of the MedicinesCommissions Pursuant to Medicines Act; 1968, 1993.429,48312. Karthik A. et al. Simultaneous estimation of paracetamoland domperidone in tablets by reverse phase HPLCmethod, Indian J Pharm Sci. 2007; 69:142:144114