Pharmaceutica Analytica Acta

Irbesartan, chemically,2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)Phenyl]phenyl}methyl)-1,3-diazospiro[4.4]non-1-en-4-one. Irbesartan, a non peptide tetrazole derivative, has anti hypertensive property [1]. It is an angiotensin II antagonist that selectively blocks the binding of an angiotensin II to the angiotensin I receptor [2]. The chemical structure of Irbesartan is shown (Figure 1).

Figure 1: Chemical structure of Irbesartan.

Irbesartan is practically insoluble in water so hydrotropic agents utilized to increase the water solubility [3]. Urea and sodium bicarbonate are the most common examples of hydrotropic agents. The solubility of various poorly water-soluble drugs was increased by hydrotropic solubilization phenomenon [4]. Literature survey reveals that various analytical methods had been developed such as HPLC [5], UV-Visible spectrophotometry [6], liquid chromatography [7] in biological fluids and in pharmaceutical formulations. To the best of our knowledge, there is no work in the literature reported about the Spectrophotometric method for the analysis of Irbesartan using hydrotropic agent. Therefore, it was thought worth wile to employ these hydrotropic solutions to extract out the drug from fine powder of tablets to carry out Spectrophotometric estimation.

Materials and methods

Instrumentation: Spectrophotometer used was Double beam UVVisible spectrophotometer with 10mm matched quartz cell Model- UV-1700 PHARMASPEC. Make – shimadzu, Japan and Analytical balance: shimadzu, Japan AX 200.

Chemicals and reagents: Irbesartan was procured from Smilax Laboratories Limited, Jeedimetla, Hyderabad-500055. All the reagents and chemicals used were of Analytical grade.

Method development

Preparation of standard stock solution and calibration curve: Standard stock solution of Irbesartan 100 μg/ml was prepared in mixed hydrotropic solution comprises 1 M sodium bicarbonate and 2 M urea (50:50% v/v). From this stock solution, appropriate dilution was made and scanned in the UV range 200-400 nm against the blank (Figure 2 and 3). The absorbance of Irbesartan was found to be 246.4 nm. The solubility of Irbesartan was increased more than 20 times in mixed hydrotropic solution as compared with distilled water. Aliquots of in the range of 10-35 μg /ml were prepared with the same solvent and scanned under Photometric mode for Absorbance at 246.4 nm. A calibration curve was plotted taking an absorbance on Y-axis against concentration of standard solution on X-axis (Table 1). The method was applied for Test sample solution and was found to be satisfactory for the analysis of dosage forms (Table 2).

Figure 2: Spectrum of NaHCO₃ and Urea.

Figure 3: Spectrum of Irbesartan in NaHCO₃ and Urea.

Table 1: Optical characteristics of the proposed method.

Table 2: Assay of IRBESARTAN tablets.

Method validation

The method was validated for different parameters like Linearity, Accuracy and Precision.

Linearity: Fresh aliquots were prepared from the stock solution (100 μg/ml) ranging from 10-35 μg/ml. The samples were scanned in UV-Visible spectrophotometer using 1 M sodium bicarbonate and 2 M urea (50:50% v/v) in water as blank. It was found that the selected drug shows linearity in the range of 10-35 μg/ml.

Accuracy: Accuracy of the method confirmed by studying recovery at 3 different concentrations for 80, 100, and 120% of these expected, in accordance with ICH guidelines, by replicate analysis. Standard drug solution was added to a pre analyzed sample solution and percentage drug content was measured. The results from study of accuracy were reported (Table 3). %Recovery = [(ct –cu)/ ca] × 100. Where ct is the total conc. of the analyte found; cu is the conc. of the analyte present in formulation; and ca is the conc. of the pure analyte added to the formulation.

Table 3: Accuracy data of the drug.

Precision: Precision (intra-day precision) of the method was evaluated by carrying out the five independent test samples of Irbesartan. The intermediate precision (inter-day precision) of the method was also evaluated using two different analyst, and different days in the same laboratory. The percent relative standard deviation (%RSD) and assay values obtained by two analysts were found to be good (Table 4).

Table 4: Precision of the Irbesartan working standards.

From the optical characteristics (Table 1) of the proposed method, Irbesartan was shown its λ_max at 246.4 nm in the solvent mixture of hydrotropic agents of 1M sodium bicarbonate and 2M urea (50:50% v/v) with a good correlation coefficient 0.9998. The percentage purity and relative standard deviation from the Assay of the tablet dosage forms (Table 2) were found to be within the limits. The accuracy data of the drug (Table 3) was shown good percentage recovery and %RSD with the range of 99.4 -101.3 and 0.2-0.4 respectively. The Inter-day and Intra-day (Table 4) precision values were found to be 0.79 and 0.57 respectively.

The proposed method for the estimation of Irbesartan was found to be simple, sensitive and reliable with good precision and accuracy. The method is specific while estimating the commercial formulations without interference of excipients and other additives.