Simultaneous Estimation of Olmesartan Medoxomil and Hydrochlorothiazide by Spectrophotometry in Tablet Formulation

 

Raman N. Kachave1, Rajendra N. Bhadane1, Rajendra Wagh2 and Deepti Jain3

1Amrutvahini College of Pharmacy, Sangamner, Dist. Ahmednagar-422608 (M.S)       2A.R.A.College oF Pharmacy, Nagaon, Dhule (MS)    3School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Bhopal-462036 (M.P)

*Corresponding Author E-mail: raman_pharma@yahoo.co.in

 

ABSTRACT:

Two precise, accurate, sensitive spectrophotometric methods has been developed and validated for the simultaneous estimation of Olmesartan Medoxomil (OLM) and Hydrochlorothiazide (HCT) in tablet formulation. In dual wavelength method absorbance difference at 254.8nm and 284nm were considered for estimation of OLM while HCT was estimated as single component at 322 nm. In simultaneous equation method estimation of OLM and HCT was carried out at 249nm and 273.5nm respectively. Regression analysis of beers plots showed good correlation in concentration range of 0-25 µg/ml for OLM and HCT respectively. Accuracy was determined by recovery studies from tablet dosages form and ranges from 98-101%. Precision of method was find out as repeatability, day to day and analyst to analyst variation and shows the values within limit (R.S.D. ≤ 2).

 

KEYWORDS: Olmesartan Medoxomil, hydrochlorothiazide, Dual Wavelength Method, Simultaneous Equation Method

 


INTRODUCTION:

Olmesartan is a selective AT1 subtype angiotensin II receptor antagonist. It blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Chemically it is 2,3-dihydroxy-2-butenyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-[p-(o-1H-tetrazol-5-yl-phenyl)benzyl]imidazole-5-carboxylate, cyclic-2,3-carbonate1. Hydrochlorothiazide 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-Sulfonamide-1,1-dioxide.

 

Hydrochlorothiazide affects the of electrolyte reabsorption it increase execration of sodium and chloride2,3. Several methods are reported for determination of HCT and OLM individually or in combination with other drugs4,11 but in literature no spectrophotometric or HPLC methods has been reported for simultaneous estimation of these two drugs. Hence sensitive and accurate spectrophotometric methods have been viewed as essential. It was validated as per ICH norm, which is mandatory also12,13.

 

MATERIAL AND METHOD:

Instrumentation:

UV-visible spectrophotometer (Shimadzu 1700)

 

Material:

Olmesartan and Hydrochlorothiazide was kindly gifted by Glenmark Pharmaceutical Ltd. and Unichem Labs Ltd. Mumbai respectively. All reagents and chemicals used were of analytical grade.

 

Standard solution:

Stock solution of 1000 μg/ml was prepared for both the drugs. From these stock solutions appropriate dilutions in the range of 0-25 µg/ml were prepared for both drugs.

 

Dual wavelength method:

HCT shows interference at the maxima of OLM. So, estimate OLM in dual wavelength method two such wavelengths were selected where HCT was showing similar absorbance i.e. 254.8nm and 284nm. The absorbance difference at this wavelength is directly proportional to the absorbance of OLM. While HCT was estimated as single component at 322nm where OLM do not show interference as shown in figure.

 

Simultaneous equation method:

To estimate OLM and HCT by simultaneous equation method 249nm and 273.5nm were selected as λ1 and λ2. The absorptivity values of OLM and HCT at λ1 and λ2 were determined. The absorbance of mix standard solution were taken at selected wavelengths and concentrations drugs were find out by simultaneous equation (Vierordt’s method)

 

                    Cx =A2ay1-A1ay2­­/ax2ay-ax1ay2……………. (1)

                    Cy = A1ax2-A2ax1/ax2ay-ax1ay2…………… (2)

 

Fig1: Overlain Spectrum of Olmesartan Medoxomil (15µg/ml) and Hydrochlorothiazide (15µg/ml) in 0.1 N NaOH.

 

Analysis of Marketed formulation:

Average weight of 20 tablets was determined, then crushed to fine powder and amount equivalent to 10mg of OLM was taken. It was dissolved in 5ml 0.1N NaOH with sonication for 3 minute. Volume was made up to 10 ml with solvent, filtered with whatmann filter paper no.41 and further dilutions were prepared. The absorbance was taken at selected wavelengths and concentrations were found out. The procedure was repeated for five times.

 

Method Validation:

The above developed method for simultaneous estimation of OLM and HCT were validated as per requirements of International Conference on Harmonization (ICH) guidelines.

 

RESULT AND DISCUSSION:

Linearity and Range:

OLM and HCT showed linearity in the range of 0-25 µg/ml respectively (Table 1 and Table 2) linear regression equation and correlation coefficient (r) are given below

Y OLM = 0.0444x +0.000762 (r2 =0.9999)

Y HCT =0.0519x – 0.00361 (r2 =0.9998)

 

TABLE 1: LINEARITY STUDY OF OLMESARTAN MEDOXOMIL

Concentration (μgml-1)

Mean absorption

± S.D.,

R.S.D. (%)

5

0.2210

0.0016

0.7153

10

0.4460

0.0048

1.0870

15

0.6614

0.0063

0.9597

20

0.8810

0.0015

0.1794

25

1.1016

0.0087

0.7933

*each reading is a mean of three replicates.

 

 

TABLE 2: LINEARITY STUDY OF HYDROCHLOROTHIAZIDE

Concentration (μgml-1)

Mean absorption

± S.D.,

R.S.D. (%)

5

0.2632

0.0015

0.5634

10

0.5216

0.0023

0.4413

15

0.7832

0.0033

0.4176

20

1.0310

0.0027

0.2656

25

1.3026

0.0032

0.2463

*each reading is a mean of three replicates.

 

Accuracy:

To test accuracy, recovery studies were performed by standard addition technique. The study was repeated for five times at three concentration level and shows values of R.S.D. ≤ 2 (Table 3).

 

TABLE 3: RESULTS OF STATISTICAL VALIDATION OF COMMERCIAL TABLET FORMULATION

Drug

Mean % found

±S.D.

% RSD

STANDARD ERROR

OLM

99.88

1.654

1.655

0.5230

HCT

99.45

07869

0.7912

0.2488

 

Precision:

Precision of method was determined as repeatability and intermediate precision. Repeatability was determined by analyzing test sample by three replicate determinations at three concentration level Intermediate precision was determined as day to day and analyst to analyst variation (Table 4 and Table 5).

 

TABLE 4: VALIDATION PARAMETERS OF DUAL WAVELENGTH METHOD

Parameters

Dual Wavelength Method

Olmesartan Medoxomil

Hydrochlorothiazide

Mean

±S.D.

R.S.D

Mean

±S.D.

R.S.D

Accuracy

102.06

1.931

1.892

99.32

1.387

1.397

Repeatability

99.08

0.194

1.331

99.26

0.126

1.477

Day to day

99.57

1.033

1.037

99.85

1.693

1.695

Analyst to Analyst

99.89

1.620

1.621

99.62

1.932

1.939

*each reading is a mean of three replicates.

 

TABLE 5: VALIDATION PARAMETERS OF SIMULTANEOUS EQUATION METHOD

Parameters

Simultaneous Equation Method

Olmesartan Medoxomil

Hydrochlorothiazide

Mean

±S.D.

R.S.D

Mean

±S.D.

R.S.D

Accuracy

100.08

0.963

0.9628

100.73

1.515

1.504

Repeatability

100.21

0.029

0.1630

98.51

0.048

0.497

Day to day

99.14

1.762

1.186

100.59

1.640

1.765

Analyst to Analyst

99.24

1.304

1.315

100.69

1.756

1.744

*each reading is a mean of three replicates.

 

CONCLUSION:

The study shows that both above developed methods are simple, accurate and precise. The use of 0.1N NaOH makes the method more economical. So proposed methods can be applicable for simultaneous estimation of OLM and HCT in commercial tablet formulations.

 

A

CKNOWLEDGEMENTS:

We would like to thank Glenmark Pharmaceuticals ltd. (Mumbai, India) and Unichem Labs Ltd. (Mumbai, India) for providing the gift samples of Olmesartan Medoxomil and hydrochlorothiazide respectively. We wish thank to School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Bhopal for providing us necessary facilities to carry out the work.

 

REFERENCES:

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Received on 12.01.2010       Modified on 20.02.2010

Accepted on 15.03.2010      © RJPT All right reserved

Research J. Pharm. and Tech.3 (4): Oct.-Dec.2010; Page 1047-1049