Estimation of Candesartan Cilexetil by Extractive Colorimetric Methods in Bulk and Pharmaceutical Dosage Form

 

Rajan V. Rele*, Prathamesh P. Tiwatane

Central Research Laboratory, D.G. Ruparel College, Matunga, Mumbai 400016.

*Corresponding Author E-mail: drvinraj@gmail.com

 

ABSTRACT:

Simple sensitive and accurate extractive spectrophotometric methods have developed for the estimation of Candesartan cilexetil in pharmaceutical dosage form. The methods are based on the formation of coloured complexes by the drug with reagents like bromophenol blue, solochrome dark blue and bromocresol green in acidic medium. The ion associated complexes were formed and quantitatively extracted under the experimental condition in chloroform. The absorbance values were measured at 420 nm, 495 nm and 430 nm respectively. The proposed methods were validated statistically. Recoveries of methods were carried out by standard addition methods. The linearity was found to be 1-10 μg/ml, 1 -12μg/ml, 1-16 μg/ ml for methods 1, 2 and 3 respectively. The low values of standard deviation and percentage RSD indicate high precision of methods. Hence these methods are useful for routine estimation of Candesartan cilexetil in tablets.

 

KEYWORDS: Candesartan cilexetil, Bromophenol blue, Solochrome dark blue, Bromocresol green, Chloroform 

 

 

INTRODUCTION:

Candesartan is an antihypertensive drug commercially available as cilexetil (cyclohexyl 1-hydroxy ethyl carbonate) ester form. It is a pro-drug and is hydrolyzed to candesartan during absorption from the gastrointestinal tract. Candesartan is a selective AT1 subtype angiotensin II receptor antagonist. It is a non-peptide, chemically described as (±)-1-Hydroxyethyl 2-ethoxy-1- [p-(o-1H-tetrazol-5-ylphenyl) benzyl]-7-benzimidazolecarboxylate, cyclohexyl carbonate (ester) Candesartan cilexetil is white to off-white crystalline powder with a molecular weight of 610.67. It is practically insoluble in water and soluble in methanol. Candesartan cilexetil is a racemic mixture containing one chiral center at the cyclohexyloxycarbonyl-oxy ethyl ester group. Following oral administration, Candesartan

 

cilexetil undergoes hydrolysis at the ester link to form the active drug, candesartan. Literature survey reveals the Spectrophotometric1-6, HPLC7-13, UPLC14 and non aqueous titration15 methods for the estimation of candesartan cilexetil. Simple, rapid and reliable UV spectrophotometric methods are developed for the determination of candesartan cilexetil. These methods can be used for the routine analysis. In the proposed methods optimization and validation of this method are reported.

 

Structure of candesartan cilexetil:

 

 

 

MATERIALS AND METHODS:

A Shimadzu -160 A double beam UV-Visible recording spectrophotometer with pair of 10mmmatched quartz cell was used to measure absorbance of solutions. A Shimadzu analytical balance was used.

 

 

Bromophenol blue, solochrome dark blue, bromocresol green, hydrochloric acid, potassium hydrogen phthalate and chloroform of A.R. grade were used in the study.

 

Preparation of standard solution and reagents:

Stock solution of Candesartan cilexetil (100μg/ml) was prepared in distilled ethanol. From this stock solution working standard (10μg/ml) was prepared by diluting 10 ml stock solution to 100ml with distilled water. 0.6% w/v solution of  bromophenol blue, 0.25% w/v solochrome dark blue and 0.2% w/v bromocresol green were prepared in distilled water respectively.

 

Potassium hydrogen phthalate buffer solution of pH 4.01was prepared in distilled water. Dilute hydrochloric acid was used to adjust desired pH of buffer solution.

 

EXPERIMENTAL:

Method 1 (with bromophenol blue):

Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 1.4ml of buffer (pH= 4.5) and 6.1ml of 0.6%w/v bromophenol blue were added. 10ml of chloroform was added to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for clear separation of the layers. The absorbance values of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λ max 420 nm).

 

Method 2 (with solochrome dark blue):

Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 4.4 ml of buffer (pH = 1.2) and 4.5ml of 0.25% w/v solochrome dark blue were added. 10ml of chloroform was added to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for clear separation of the layers. The absorbance values of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λ max=495 nm).

 

Method 3 (with bromocresol green):

Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 1.5ml of buffer (pH= 3.5) and 3.5ml of 0.02% w/v bromocresol green were added. 10ml of chloroform was added to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for clear separation of the layers. The absorbance values of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λmax =430 nm).

 

Estimation from tablets:

Twenty tablets were weighed accurately and average weight of each tablet was determined. Powder equivalent to 10mg of Candesartan cilexetil was weighed and transferred in 100ml of volumetric flask. A 30ml of ethanol was added and sonicated for 15 minutes and filtered. The filtrate and washing were diluted up to the mark with ethanol to give concentration as 100μg/ml. Such solution was used for analysis.

 

 

Table 1: Values of results of optical and regression of drug

Parameter

Bromophenol blue 

Solochrome dark blue

Bromocresol green

Detection Wavelength (nm)

420

495

430

Beer Law Limits (µg/ml)

1-10

1-12

2-16

Correlation coefficient(r2)

0.9999

0.9999

0.9999

Regression equation (y=b+ac)

 

 

 

Slope (a)

0.0501

0.0225

0.0399

Intercept (b)

0.0012

0.00006

0.0025

 

RESULTS:

The extractive spectrophotometric methods are popular due to their sensitivity in assay of the drug and hence ion pair extractive spectrophotometric methods have gain considerable attention for quantitative determination of many pharmaceutical preparations. These proposed methods are extractive spectrophotometric methods for the determination of Candesartan cilexetil by using chloroform as solvent from its formulations i.e. tablets. The colour ion pair complexes formed are very stable. The working conditions of these methods were established by varying one parameter at time and keeping the other parameters fixed by observing the effect produced on the absorbance of the colour species. The various parameters involved for maximum colour development for these methods were optimized. The proposed methods were validated statistically and by recovery studies. The molar absorptivity show the sensitivity of methods while the precision was confirmed by % RSD (relative standard deviation). The optical characteristics such as absorption maxima (nm), molar absorptivity (l -mole-1 cm-1), co-relation coefficient (r) were calculated and are also summarized. Assay results of recovery studies are given in table 2 (A,B,C).

 

 

 

 

 

 

Table no 2: A (bromophenol blue)

Amount of Sample Added in (µg/ml)

Amount of Standard Added in (µg/ml)

Total amount recovered

Percentage recovery (%)

Standard deviation

Percentage of relative standard deviation (C.O.V.)

1

0

1.002527

100.2527

0.00148

0.147609

2

1

2.008403

100.4202

0.019135

0.952762

3

2

3.002801

100.0934

0.030855

1.027532

4

3

4.002801

100.07

0.020962

0.523675

 

 

 

 

Mean=  0.018108

Mean=  0.662894

 

Table no 2: B (solochrome dark blue)

Amount of Sample Added in (µg/ml)

Amount of Standard Added in (µg/ml)

Total amount recovered

Percentage recovery (%)

Standard deviation

Percentage of relative standard deviation (C.O.V.)

2

0

2.008254

100.4127

0.005979

0.297701

2

2

4.00654

100.1635

0.003392

0.084655

2

4

6.006984

100.1164

0.003497

0.058213

2

6

8.017143

100.2143

0.012683

0.158193

 

 

 

 

Mean= 0.006387

Mean= 0.149691

 

Table no 2:C (bromocresol green)

Amount of Sample Added in (µg/ml)

Amount of Standard Added in (µg/ml)

Total amount recovered

Percentage recovery (%)

Standard deviation

Percentage of relative standard deviation (C.O.V.)

2

0

2.003523

100.1761

0.002407

0.120121

2

2

4.004932

100.1233

0.002014

0.050277

2

4

6.021279

100.3546

0.002489

0.041344

2

6

8.020081

100.251

0.00361

0.045012

 

 

 

 

Mean=  0.00263

Mean=  0.064189

Results are in good in agreement with labelled value.

 

DISCUSSION:

The percent recovery obtained indicates non-interference from the common excipients used in the formulation. The reproducibility, repeatability and accuracy of these methods were found to be good, which is evidenced by low standard deviation. The proposed methods are simple, sensitive, accurate, precise and reproducible. They are directly applied to drug to form chromogen. Hence they can be successfully applied for the routine estimation of drug, in bulk and pharmaceutical dosage form even at very low concentration and determination of stability of drug in formulation such as tablets. The strong recommendation is made here for the proposed methods for determination of Candesartan cilexetil from its formulation.

 

ACKNOWLEDGMENT:

Authors express sincere thanks to the Principal, of D. G. Ruparel College, Mumbai.

 

REFERENCES:

1.      Nawal A. AL-Arfaj, Wedad A. AL-Onazi and Amina M. EL-Brashy. Spectrophotometric Determination of Candesartan Cilexetil in Presence of Its Alkaline Induced Degradation Product. Asian Journal of Chemistry. 2011; 23(4): 1696-1700.

2.      K. K. Pradhan, U. S. Mishra, S. Patnnaik, C. K. Panda, K. C. Sahu. Development and Validation of a Stability-indicating UV Spectroscopic Method for Candesartan in bulk and formulations. Indian Journal of Pharmaceutical Sciences. 2011; 73(6): 693-696.

3.      Anjan Paudel, Ameeduzzafar, Farhan Jalees Ahmad, Mohd Qumbar, Chetan Dhal, Asgar Ali. Stress degradation studies on candesartan cilexetil bulk drug and development of validated method by UV spectrophotometry in marketed tablet. World Journal of Pharmaceutical Science. 2014; 3(3): 3975-3986.

4.      Kalyani G., Vaishnav Y, Deshmukh S.V, Sahu R.  Stability Indicating Method Development and Validation of Candesartan in Bulk and Pharmaceutical Dosage Form by Derivative Spectrophotometric Method (First Order). International Journal of Pharmamedix India. 2013; 1(2): 222-232.

5.      Rele Rajan V. UV spectrophotometric estimation of candesartan cilexetil by area under curve and second order derivative methods in bulk and pharmaceutical dosage form. Der Pharmacia Lettre. 2015; 7(6):237-243.

6.      Rele Rajan V. Tiwatane Prathmesh P. Determination of Candesartan cilexetil from pharmaceutical dosage form by extractive ion pair complex colorimetric method. Asian J. Research Chem. 2025; 18(4): 243-245. DOI: 10.52711/0974-4150.2025.00037.

7.      Naga Dileep P.V, Putta Rajesh Kumar, Salahuddin Md., Shanta Kumar S.M. Candesartan cilexetil analytical method development and validation studies by reverse phase HPLC technique. International Journal of Pharmaceutical Frontier Research. 2012; 2(3): 36-43.

8.      R Revathi, T Ethiraj, Jhansi L. Marreddy, V Ganeshan. Development and validation of a dissolution test for Candesartan cilexetil in tablet forms using reverse phase – High performance liquid chromatography. Pharm Education Res. 2011; 2(2):  71-77.

9.      V. Kamalakkannan, A. Puratchikody, K. Masilamani, T. Saraswathy.  Analytical method development and validation for Candesartan Cilexetil as bulk drug and in pharmaceutical dosage forms by HPLC. Der Pharmacia Lettre. 2011; 3(3): 286-296.

10.   Amit Asati, Anita Shinde, Suman Malik, K.C. Asati. Analytical Assay Development and Validation for Estimation of Trityl Candesartan in Bulk Drug by of Reverse Phase Liquid Chromatography. Int. J. Pharm. Sci. Rev. Res. 2014; 26(1): 169-173.

11.   Syeda Kulsum, G Vidya Sagar, K. Nagalakshmi, R. Snehalatha.  Development and validation of RP-HPLC method for estimation of candesartan from tablet dosage form. World of Pharmacy and Pharmaceutical Science. 2014; 3(4): 781-786.

12.   Manisha P Puranik, Sailesh J Wadher, Ashish L Kosarkar, Pramod G Yeole. Method Development and Validation of Candesartan cilexetil by RP-HPLC. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2014; 3(3): 1227-1230.

13.   Manju Latha Y.B. Gowri Shankar D. stability indicating RP-HPLC method for determination of candesertan in pure and pharmaceutical formulation. International Journal of Pharmacy and Industrial Research. 2011; 1(4): 344-349.

14.   Gunda Srinivas, Kakumani Kishore Kumar, Gangaram V. Kanumula, M. Vishnu Priya1, K. Mukkanti, A Stability Indicating UPLC Method for Candesartan in Bulk Drug Samples. American Journal of Analytical Chemistry. 2012; 3: 704-709.

15.   Rele Rajan V. A validated non-aqueous potentiometric titration method for quantitative determination of candesartan cilexetil from pharmaceutical preparation. Int. J. Chem. Sci. 2016; 14(4): 2696-2702.

 

 

 

Received on 14.08.2025      Revised on 29.08.2025

Accepted on 19.09.2025      Published on 30.09.2025

Available online from October 07, 2025

Asian J. Research Chem.2025; 18(5):324-326.

DOI: 10.52711/0974-4150.2025.00049

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