Edition: BP 2025 (Ph. Eur. 11.6 update)
Irbesartan Tablets
General Notices
Action and use
Angiotensin II (AT1) receptor antagonist.
DEFINITION
Irbesartan Tablets contain Irbesartan.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of irbesartan, C25H28N6O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Dissolve a quantity of the powdered tablets containing 0.3 g of Irbesartan in 10 mL of methanol with the aid of ultrasound. Filter through a Whatman GF/C filter and then through a 0.45-µm filter. Evaporate the filtrate to dryness under a stream of nitrogen and dry the residue at 60° for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of Irbesartan (RS 467). Disregard any bands occurring between 1125 and 1000 -1 cm .
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the requirements in the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary to produce a solution containing 0.0083% w/v of Irbesartan, at the maximum at 254 nm, Appendix II B using 0.1M hydrochloric acid in the reference cell.
(2) Measure the absorbance of a 0.0083% w/v solution of irbesartan BPCRS using 0.1M hydrochloric acid in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of irbesartan, C25H28N6O in the medium from the absorbances obtained and using the declared content of C25H28N6O in irbesartan BPCRS.
LIMITS
The amount of irbesartan released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Prepare a 0.025M solution of sodium dihydrogen orthophosphate monohydrate, adjusted to pH 3.2 with orthophosphoric acid (solvent A).
(1) To a quantity of the powdered tablets containing 62.5 mg of Irbesartan, add 125 mL of methanol and mix with the aid of ultrasound. Add 100 mL of solvent A and shake. Dilute to 250 mL with solvent A, mix and filter (a 0.45-µm filter is suitable).
(2) Dilute 1 volume of solution (1) to 50 volumes with equal volumes of methanol and solvent A. Dilute 1 volume of this solution to 10 volumes with solvent A.
(3) 0.025% w/v of irbesartan impurity A BPCRS in methanol.
(4) To 25 mg of irbesartan BPCRS, add 50 mL of methanol and mix with the aid of ultrasound, add sufficient solvent A to produce 100 mL.
(5) Dilute 1 volume of solution (3) to 200 volumes with solution (4).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.0 mm) packed with octadecylsilyl silica gel for chromatography (3.5 µm) (Waters SunFire C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 0.6 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 10 µL of solutions 1, 2 and 5.
MOBILE PHASE
Mobile phase A 42 volumes of acetonitrile R1 and 58 volumes of solvent A.
Mobile phase B 20 volumes of solvent A and 80 volumes of acetonitrile R1.
| Time (Minutes) | Mobile phase A (%) | Mobile phase B (%) | Comment |
|---|---|---|---|
| 0–6 | 100 | 0 | isocratic |
| 6–11 | 100→0 | 0→100 | linear gradient |
| 11–12 | 0 | 100 | isocratic |
| 12–13 | 0→100 | 100→0 | linear gradient |
| 13–15 | 100 | 0 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions the relative retention, with reference to Irbesartan (retention time = about 5 minutes), of impurity A is about 0.8.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (5), the resolution factor between the peaks due to irbesartan and irbesartan impurity A is at least 4.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to irbesartan impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any other secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Prepare a 0.025M solution of sodium dihydrogen orthophosphate monohydrate, adjusted to pH 3.2 with orthophosphoric acid (solvent B).
(1) To a quantity of the powdered tablets containing 62.5 mg of irbesartan, add 125 mL of methanol and mix with the aid of ultrasound. Add 100 mL of solvent B and shake. Dilute to 250 mL with solvent B, mix and filter (a 0.45-µm filter is suitable).
(2) To 25 mg of irbesartan BPCRS, add 50 mL of methanol and mix with the aid of ultrasound. Dilute to 100 mL with solvent B.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used with a detection wavelength of 250 nm.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (2), the symmetry factor of the peak due to irbesartan is between 0.8 and 2.0.
DETERMINATION OF CONTENT
Calculate the content of C25H28N6O in the tablets using the declared content of C25H28N6O in irbesartan BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurity A listed under Irbesartan.
