Research Article ISSN: 0974-6943
Tripti Sharma et al. / Journal of Pharmacy Research 2010, 3(7),1553-1555
Available online through www.jpronline.info Difference Spectrophotometric Method for the Determination of Olmesartan Medoxomil in Tablets Tripti Sharma1 *, S.C.Si 1 and D.Gowrishankar2 , 1 School of Pharmaceutical Sciences, Kalinga Nagar, Ghatikia,Bharatpur, Bhubaneswar – 751003 Orissa 2 Pharmaceutical Analysis and Quality Assurance Division,College of Pharmaceutical Sciences,Andhra University, Visakhapatnam, India.
Received on: 15-04-2010; Revised on: 12-05-2010; Accepted on:13-06-2010 ABSTRACT A simple, rapid and sensitive difference spectrophotometric method was used for the determination of Olmesartan Medoxomil in pharmaceutical dosage forms. The method is based on the induced spectral changes upon changing the pH of the medium that differ in their UVspectra. Difference spectrum, obtained by keeping Olmesartan medoxomil in 0.1N HNO3 in reference cell and Olmesartan medoxomil in 0.1N NaOH in sample cell, showed two characteristic peaks at 259nm and 290nm with positive and negative absorbance respectively. Difference of absorbance between these two maxima was calculated to find out the amplitude, which was plotted against concentration. The calibration curve is linear over the concentration range of 10-50µg/ml (r2 = 0.999), with a detection limit of 0.15µg/ml. The method was successfully applied to the commercial pharmaceutical drug without interference from common ingredient accompanying the drug. The result statistically compared with those obtained by the reference method. Key words: Olmesartan Medoxomil, Difference, Spectrophotometry, Tablets, excipients.
INTRODUCTION Olmesartan medoxomil (OLM) (Fig-1) 5-methyl-2-oxo-1,3-dioxolen4yl)methyl-4-(1-hydrxy-1-methylethyl)-2-propyl-1-[4-(2-(tetrazole-5yl)phenyl}methylimidazole-5-carboxylate is considered the latest angiotensin II receptor blocker approved in April2002 by the Food and drug Administration (FDA) for the treatment of hypertension, OLM is used, either alone or in combination with other drugs, to treat high blood pressure. This antihypertensive is prodrug that is rapidly and completely deesterified to the active metabolite OLM by both aryl esterase and albumin during gastrointestinal absorption.[1, 2 ]
ence spectrophotometric assay are that the measured value is the difference absorbance (?A) between two equimolar solutions of the analyte in different chemical forms, which exhibit difference spectral characteristics. The simplest and most commonly employed technique for altering the spectral properties of analyte is the adjustment of the pH by means of aqueous solution of acids, alkali. Experimental MATERIALAND METHOD: A Jasco UV-VIS Spectrophotometer 630 with 1.0 cm matched quartz cells was used. OLM bulk drug was obtained from Cipla, Mumbai, India, Olmat-20 tablet (20mg) were obtained from the market (manufactured by Micro labs limited, Pondicherry) and OM-Pin-20 (20mg) manufactured by Lupin Ltd, Mumbai, India . Sodium hydroxide and nitric acid (were from Merck, Mumbai, India) (0.1M Solution), Water was always double distilled. Procedure
Fig.1 Chemical structure of Olmesartan Medoxomil
Calibration: Stock OLM solution was prepared by dissolving 100mg of working standard in 100ml of methanol. Working standard solutions with concentration ranging from 10-50µg/ml in methanol were prepared by transferring appropriate volume of stock solution to 10ml volumetric flask in duplicate. The volume was then adjusted with 0.1M HNO3 and 0.1M NaOH to give a series of equimolar solutions of Olmesartan Medoxomil in different pH medium. Difference spectra were obtained by keeping acidic form (in 0.1m HNO3 ) in reference cell and basic form (in 0.1M NaOH) in sample cell. Difference of absorbance between 259nm and 290nm was calculated to find out the amplitude (Table1)
There is no reference for determination of this drug in both bulk and dosage forms in official compendia. A literature survey reveals that several methods were reported for the estimation of OLM in plasma, serum and tablets by liquid chromatography.[3-5]. The use of LC hyphenated techniques for identification of degradation products in stressed tablets of OLM was published in.[6] OLM has been determined in biological fluids using LC coupled to fluorescence and tandem mass spectrometry.[7-9] There are also reports on spectrophotometry and capillary electrophoresis for the quantitative determination of this drug in coated tablets.[10,11]The idea of the present work is to provide simple, sensi- Table .1.Difference Standard curve of Olmesartan Medoxomil tive and rapid spectrophotometric determination of OLM, the method is free Amplitude** from interference when excipients are present. The essential features of a differ- Concentration( µg/ml) Absorbance* λmax λmin
*Corresponding author. Tripti Sharma, School of Pharmaceutical Sciences, Kalinga Nagar, Ghatikia, Bharatpur, Bhubaneswar – 751003, Orissa. Tel.: + 91-0674-2351865 Telefax: +91-0674 - 2384209 E-mail:
[email protected]
10 20 30 40 50
0.075 0.156 0.257 0.341 0.480
-0.076 -0.106 -0.142 -0.182 -0.174
0.151 0.262 0.399 0.523 0.654
*= average of three determination, **= sum of the absorbances at 259nm and 290nm,Correlation co-efficient =0.999, slope = 0.012 , intercept = 0.017
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Tripti Sharma et al. / Journal of Pharmacy Research 2010, 3(7),1553-1555 Procedure for the assay of Olmesartan Medoxomil in tablet: The average mass of 10 tablets was determined and was ground in a mortar. An amount of powder (accurately weighed) equivalent to 10mg OLM was transferred in 100ml volumetric flask and made up to the mark with methanol. The content of the flask was sonicated for 30min and then the solution was filtered through Whatmann no-1 filter paper. The first filtrate was removed then 3ml of the filtrate was transferred to 10ml volumetric flask in duplicate. The volume was then adjusted with 0.1M HNO3 and 0.1 M NaOH .The absorbance difference (?A) between the acidic solution and equimolar 0.1M NaOH solution was measured at 259nm and 290nm by placing acidic solution as reference and basic solution as sample.The content of the tablet is calculated from the calibration curve or using the corresponding regression equation in (Table-2)
Calibration plot: A plot of difference absorbance vs OLM concentration was seen to be linear over the concentration range 10-50µg/ml (r2 =0.999) with a slop of 1.2×10-2 and intercept of 1.7× 10 -2 (fig 4).The limit of detection (LOD) was determined by establishing the minimum level at which the analyte can be detected. The LOD was found to be 0.15µg/ml, according to the 3s/m definition, where s is the standard deviation ( n =5) of the signal from 40µg/ml OLM aliquots and m is the slop of the calibration graph.
Table -2 Determination of OLM in Commercial Tablets Using Difference Spectrophotometric Method.
Meana SD RSD b Recoveryc%
PinOM -20(20mg)
Olmat-20(20mg)
19.95± 0.034 0.170 99.75
19.89± 0.0776 0.390 99.45
Fig 4 The difference absorption calibration curve of OLM in 0.1 M NaOH and 0.1 m HNO3. The linear regression equation is y= 0.012x + 0.017( r2 = 0.999) .
a
Mean of five values RSD, relative std deviation c Recovery(%) = (Amount found/ Amount taken)×100 b
RESULT AND DISCUSSION This work describes a simple pH induced difference spectrophotometric method for the determination OLM in tablets (in the presence of excipients).The absorbance spectra of equimolar solutions of OLM in 0.1M HNO3 (pH 1) and 0.1M NaOH (pH 13), are shown in Fig-2 1
Interference studies: The effect of foreign substances, inactive excipient material that commonly accompanying the drug in pharmaceutical formulation such as tablets (starch, mannitol, cellulose, PVP, magnesium stearate, titanium dioxide) was studied by comparision of the absorption spectra of OLM in standard solution and in solution at some extract (for example: olmat20, OMPin-20 tablets). The obtained absorption spectra are identical. Fig 5 confirmed that tablet excipient have no interference effect on the measurement of ?A Values. 1
0.5
0 .5
Abs 0
Abs
0
- 0 .5 -0 . 5 250
300 350 Wave length [nm]
400
Fig 2 Absorption spectra of equimolar solution of OLM (40 µg/ml) in 0.1M HNO3 and 0.1 M NaOH.
Fig.3 shows the difference absorption spectrum of OLM solution. It is generated by measure the absorbance of equimolar OLM solution at pH 13 (in 0.1M NaOH) in sample cell against the OLM at pH 1 (in 0.1M HNO3) form in reference cell. 1
3 00 35 0 W a v e l e n g th [n m ]
400
Fig 5 The difference absorption spectra of equimolar solution of OLM (30µg/ml) in 0.1M HNO3 vs 0.1M NaOH, Using standard solution (—), Olmat-20(——), Pin-OM-20(—-).
Analysis of commercial tablets: Difference spectrophotometric method was applied to two brands of OLM tablet well known in the market. The result of analysis is reported in table 2. The reproducibility of the method was checked by five replicate determinations and then the Relative standard deviation (RSD) is calculated.
0.5
Abs
-1 240
0
CONCLUSION
-0.5 -1
250
300 350 Wavelength [nm]
400
Fig 3 The difference absorption spectrum of equimolar solution of OLM (40µg/ ml) in 0.1M HNO3 vs 0.1M NaOH.
The method is found to be simple, economical, selective and sensitive. The statistical parameters clearly indicate the reproducibility and accuracy of the method. Analysis of OLM in its dosage forms showed no interference from the common excipients and additives. Difference spectrophotometry by indicating pH of the medium may be recommended for routine and quality control analysis of the investigated drug in tablets.
Journal of Pharmacy Research Vol.3.Issue 7.July 2010
1553-1555
Tripti Sharma et al. / Journal of Pharmacy Research 2010, 3(7),1553-1555 ACKNOWLEDGEMENT
5.
The authors are thankful to Cipla Pvt, Ltd, Mumbai for providing the free gift samples of Olmesartan medoxomil for the research work.
6.
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Source of support: Nil, Conflict of interest: None Declared
Journal of Pharmacy Research Vol.3.Issue 7.July 2010
1553-1555
