Action and use
Angiotensin II (AT1) receptor antagonist.
DEFINITION
Olmesartan Tablets contain Olmesartan Medoxomil.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of olmesartan medoxomil, C29H30N6O6
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Shake a tablet in sufficient of 60% v/v of acetonitrile to prepare a solution containing 0.02% w/v of Olmesartan
Medoxomil and mix with the aid of ultrasound. Centrifuge and dilute 5 mL of the supernatant liquid to 100 mL with 60% v/v of acetonitrile. The light absorption of the resulting solution, Appendix II B, in the range 200 to 360 nm exhibits a maximum at about 258 nm.
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
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 a solution prepared by dissolving 6.80 g of potassium dihydrogen orthophosphate and 0.944 g of sodium hydroxide in water and dilute to 1000 mL with water, at a temperature of 37°, as the dissolution medium.
PROCEDURE
(1) After 45 minutes, withdraw a sample of the medium, filter and dilute the filtrate with sufficient of the dissolution medium to give a solution expected to contain about 0.001% w/v of Olmesartan Medoxomil. Measure the absorbance of this solution, Appendix II B, at 258 nm using dissolution medium in the reference cell.
(2) Measure the absorbance of a 0.001% w/v solution of olmesartan medoxomil BPCRS using dissolution medium in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of olmesartan medoxomil, C29H30N6O6, in the medium from the absorbances obtained and using the declared content of C29H30N6O6, in olmesartan medoxomil BPCRS.
LIMITS
The amount of olmesartan medoxomil 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.
(1) Shake a quantity of tablets in sufficient of 90% v/v of acetonitrile to prepare a solution containing 0.1% w/v of Olmesartan Medoxomil, mix with the aid of ultrasound, centrifuge and filter the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 50 volumes with 90% v/v of acetonitrile and dilute 1 volume of the resulting solution to 10 volumes with the same solvent.
(3) Dissolve 5 mg of olmesartan medoxomil for system suitability EPCRS in 90% v/v of acetonitrile and dilute to 5 mL with the same solvent.
CHROMATOGRAPHIC CONDITIONS
(a) A stainless steel column (10 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (3.5 μm) (Waters Symmetry C8 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 250 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
Mobile phase A 20 volumes of acetonitrile and 80 volumes of a 0.015M potassium dihydrogen orthophosphate buffer solution prepared in the following manner. Dissolve 4.08 g of potassium dihydrogen orthophosphate in water, dilute to 2000 mL and adjust the pH to 3.4 with a 0.173% w/v solution of orthophosphoric acid.
Mobile phase B 20 volumes of a 0.015M potassium dihydrogen orthophosphate buffer solution prepared as described under mobile phase A, and 80 volumes of acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-10 | 75 | 25 | isocratic |
| 10-35 | 75→0 | 25→100 | linear gradient |
| 35-45 | 0 | 100 | isocratic |
| 45-60 | 0→75 | 100→25 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions the retention times relative to olmesartan medoxomil (retention time, about 10 minutes) are: impurity A, about 0.2; impurity B, about 0.7; impurity C, about 1.5.
SYSTEM SUITABILITY
The test is not valid unless in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity B and olmesartan medoxomil is at least 3.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity A is not greater than 4.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.9%);
the area of any peak corresponding to impurity C is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
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 secondary peaks is not greater than 8.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.7%).
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
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) To 10 whole tablets add 80 mL of 60% v/v acetonitrile and shake. Dilute to 100 mL with 60% v/v acetonitrile and dissolve with the aid of ultrasound. Centrifuge the resulting solution and dilute a suitable quantity of the supernatent with 60% v/v acetonitrile to produce a solution containing 0.004% w/v Olmesartan medoximil.
(2) 0.004% w/v of olmesartan medoxomil BPCRS in 60% v/v of acetonitrile.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (L-Column ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 249 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
34 volumes of acetonitrile and 66 volumes of a 0.015M potassium dihydrogen orthophosphate buffer solution prepared in the following manner. Dissolve 4.08 g of potassium dihydrogen orthophosphate in water, dilute to 2000 mL and adjust the pH to 3.4 with a 0.173% w/v solution of orthophosphoric acid.
DETERMINATION OF CONTENT
Calculate the content of C29H30N6O6 in the tablets from the chromatograms obtained using the declared content of C29H30N6O6 in olmesartan medoxomil BPCRS
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Olmesartan Medoxomil.
