Action and use
Selective inhibitor of cyclic GMP-specific phosphodiesterase type V with vasodilator action; treatment of erectile dysfunction.
DEFINITION
Vardenafil Orodispersible Tablets contain Vardenafil Hydrochloride Trihydrate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of vardenafil, C23H32N6O4S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following.
(1) Disperse a quantity of the powdered tablets containing the equivalent of 20 mg of Vardenafil Hydrochloride Trihydrate in 100 mL of a solution of 1 volume of acetonitrile and 4 volumes of 0.1M hydrochloric acid and filter.
(2) 0.02% vardenafil hydrochloride EPCRS in a solution of 1 volume of acetonitrile and 4 volumes of 0.1M hydrochloric acid.
CHROMATOGRAPHIC CONDITIONS
(a) Use precoated silica gel F254 HPTLC plates (Merck silica gel 60 F254 HPTLC plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 8 cm.
(e) After removal of the plate, dry in air, and examine under ultraviolet light (254 nm).
MOBILE PHASE
1 volume each of acetone, of cyclohexane and of methanol.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and size to that in the chromatogram obtained with solution (2).
B. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as the principal peak in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Solvent A 1 volume of acetonitrile and 4 volumes of 0.1M hydrochloric acid.
(1) Disperse a quantity of powdered tablets containing the equivalent of 10 mg of vardenafil in 50 mL of solvent A with the aid of ultrasound and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with solvent A.
(3) Dilute 1 volume of solution (2) to 10 volumes with solvent A.
(4) 0.015% w/v of vardenafil for system suitability EPCRS solvent A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Zorbax Extend C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 245 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
Mobile phase A: 0.08% w/v of ammonium acetate in 90 volumes of water and 10 volumes of acetonitrile.
Mobile phase B: 0.08% w/v of ammonium acetate in 10 volumes of water and 90 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions, the relative retention times with reference to vardenafil (retention time about 8 min) are: impurity B, about 0.2; impurity 1, about 0.5; impurity 2, about 0.55; impurity A, about 0.6 and impurity C, about 1.3.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to vardenafil and impurity A is not less than 5.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak due to impurity 1 is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);
the area of any peak due to impurity B or impurity 2is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (3) (0.5%);
the area of any other secondary peak is not greater than 2 times the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);
the sum of the areas of all secondary peaks is not greater than 2 times the area of the principal peak in the chromatogram obtained with solution (2) (2%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Solvent A: 1 volumes of acetonitrile and 4 volumes of 0.1M hydrochloric acid.
(1) Disperse a quantity of powdered tablets containing the equivalent of 10 mg of vardenafil in solvent A with the aid of ultrasound, dilute to 50 mL and filter.
(2) 0.0215% of vardenafil hydrochloride EPCRS in solvent A.
(3) 0.015% w/v of vardenafil for system suitability EPCRS in solvent A.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to vardenafil and impurity A is not less than 5.0.
DETERMINATION OF CONTENT
Calculate the content of vardenafil, C23H32N6O4S, using the declared content of C23H32N6O4S, HCl, in vardenafil hydrochloride EPCRS. Each mg of vardenafil hydrochloride EPCRS is equivalent to 0.9306 mg of vardenafil.
STORAGE
Vardenafil Orodispersible Tablets should be stored at a temperature not exceeding 25° and protected from moisture and light.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Vardenafil Hydrochloride Trihydrate and:
1. 1-Ethyl-4-{4-ethoxy-3-[5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl]benzenesulfonyl}piperazine N1-oxide
2. 2-[2-Ethoxy-5-(piperazine-1-sulfonyl)phenyl]-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
