Determination of Candesartan cilexetil from pharmaceutical dosage form by extractive ion pair complex colorimetric method
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 colorimetric method was developed for the estimation of Candesartan cilexetil in Pharmaceutical dosage forms. The method was based on the formation of colored ion pair complexes by the drugs with thiocynate ions. These ion pair complexes were quantitatively extracted under the experimental condition in chloroform. The absorbance values were measured at 622 nm respectively. The proposed method was validated statistically. A recovery of method was carried out by standard addition methods. The Beer’s law ranges were found to be 2-18 μg/ml, respectively. The low values of standard deviation and percentage RSD indicate high precision of method. Hence the method is useful for routine estimation of Candesartan cilexetil in tablets respectively.
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 Spectrophotometric 1-5, HPLC 5-12, UPLC 13 and non aqueous titration14 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 10mm matched quartz cell was used to measure absorbance of solutions. A Shimadzu analytical balance was used.
Cobalt nitrate, Ammonium thiocynate, 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 ethanol. From this stock solution working standard (10μg/ml) was prepared by diluting 10 ml stock solution to 100 ml with distilled water.
EXPERIMENTAL
Preparation of solutions
Stock solutions of Candesartan cilexetil (100 μg /ml) were prepared in ethanol.
From these stock solutions, working standard solutions (10 μg/ ml) were prepared by diluting 10 ml stock solution to 100 μg/ ml with distilled water.
Preparation of reagents
Cobalt thiocynate was prepared by dissolving cobalt nitrate and ammonium thiocynate in 1:2 molar proportions in distilled water.
Experimental:
Into a series of separating funnels appropriate amount of the working standard drug solutions were pipetted out. To each funnel 1.6 ml of cobalt thiocynate complex solution was added along with 10 ml of chloroform to each funnel. The solutions were shaken for thorough mixing of the two phases and were allowed to stand for separation of the layers. The absorbance value of the chloroform layers were measured against their respective reagent blank at the wavelength of the maximum absorbance (λ max 622 nm).
Estimation from tablets
Twenty tablets of Candesartan cilexetil were weighed accurately. Average weight of each tablet of candesartan cilexetil was determined. Tablets were crushed into fine powder. An accurately weighed quantity of powder equivalent to 10 mg of candesartan cilexetil was transferred into a beaker and it was shaken with 50 ml of ethanol and filtered. The filtrate and the washing were collected in a 100.0 ml volumetric flask. This filtrate and the washing were diluted up to the mark with ethanol to obtain final concentration as 100 μg /ml. A 10 ml. of this solution was further diluted to give 10 μg /ml. Such solutions were further used for estimation of candesartan cilexetil respectively. Appropriate aliquots of drug solution were taken. The individual assay procedures were carried out for the estimation of drug contents in tablets. The concentration of the drug in the tablets was calculated using calibration curve. Fig. no.1
Fig. no: 1. Calibration curve
The recovery experiment was carried out by standard addition method. The values of optical and regression terms of analysis are given in table no1.
Table 1: Values of results of optical and regression of drug
|
Parameter |
Values |
|
Detection Wavelength (nm) |
622 |
|
Beer Law Limits (µg/ml) |
2-18 |
|
Correlation coefficient(r2) |
0.9999 |
|
Regression equation (y=b+ac) |
|
|
Slope (a) |
0.012 |
|
Intercept (b) |
0.00009 |
RESULT:
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. The colour ion –pair complexes are formed and 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 optical characteristics such as absorption maxima (nm), correlation coefficient (r) and were calculated and are also summarized in table I. Assay results of recovery studies are given in table no. 2.
Table no 2: Results of recovery studies
|
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 |
2.019048 |
100.9524 |
0.017156 |
0.849684 |
|
2 |
2 |
4.020238 |
100.506 |
0.011644 |
0.289634 |
|
2 |
4 |
6.027381 |
100.4563 |
0.011501 |
0.190814 |
|
2 |
6 |
8.028571 |
100.3571 |
0.009449 |
0.117694 |
|
|
|
|
|
Mean= 0.012437 |
Mean=0.361956 |
Results are in good in agreement with labelled value. The percent recovery obtained indicates non interference from the common excipient used in the formulation.
DISCUSSION:
The reproducibility, repeatability and accuracy of these methods were found to be good, which is evidenced by low values of standard deviations. Colorimetric methods suggested in literature were applied in UV region, need costly reagents for development of chromogen and useful in higher concentration. The proposed methods are simple, sensitive, accurate, precise, and reproducible applicable to even very low concentration as compare to previous methods suggested in literature. They are directly applied to drug to form chromogen. Hence they can be successfully applied for the routine estimation of Candesartan cilexetil in bulk and pharmaceutical dosage form even at very low concentration 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, D. G. Ruparel College for providing necessary facilities and encouragement for research work.
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Received on 28.05.2025 Revised on 14.06.2025 Accepted on 30.06.2025 Published on 12.08.2025 Available online from August 18, 2025 Asian J. Research Chem.2025; 18(4):243-245. DOI: 10.52711/0974-4150.2025.00037 ©A and V Publications All Right Reserved
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