Vardenafil Orally Disintegrating Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Vardenafil Orally Disintegrating Tablets contain an amount of Vardenafil Hydrochloride equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of vardenafil (C₂₃H₃₂N₆O₄S).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

[NOTE-Protect all solutions containing vardenafil from light.]

Solution A: 0.8 g/L of ammonium acetate in a mixture of acetonitrile and water (10:90), prepared as follows. Dissolve the ammonium acetate in water, and then add acetonitrile to volume.

Solution B: 0.8 g/L of ammonium acetate in a mixture of acetonitrile and water (90:10), prepared as follows. Dissolve the ammonium acetate in water, and then add acetonitrile to volume.

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and 0.1 N hydrochloric acid (20:80)

System suitability solution: 0.15 mg/mL of USP Vardenafil System Suitability RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution: 0.22 mg/mL of USP Vardenafil Hydrochloride RS, equivalent to 0.2 mg/mL of vardenafil, in Diluent. Sonicate to dissolve, if necessary.

Sample solution: Nominally 0.2 mg/mL of vardenafil in Diluent prepared as follows. Transfer Tablets (NLT 5) into a suitable volumetric flask and add 80% of the flask volume of Diluent. Sonicate to dissolve, and dilute with Diluent to volume. Use the clear supernatant for analysis.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 245 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 5 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for 7-methyl vardenafil and vardenafil are 0.6 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 5.0 between vardenafil and 7-methyl vardenafil, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.5% from 6 replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of vardenafil (C₂₃H₃₂N₆O₄S) in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) ×100

r_U = peak response of vardenafil from the Sample solution

r_S = peak response of vardenafil from the Standard solution

C_S = concentration of USP Vardenafil Hydrochloride RS in the Standard solution (mg/mL) s

C_U = nominal concentration of vardenafil in the Sample solution (mg/mL)

M_r1 = molecular weight of vardenafil, 488.61

M_r2 = molecular weight of anhydrous vardenafil hydrochloride, 525.07 

Acceptance criteria: 95.0%-105.0%

4 PERFORMANCE TESTS

DISINTEGRATION (701): NMT 30 s

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

[NOTE-Protect all solutions containing vardenafil from light.]

Solution A, Solution B, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution: 0.1 mg/mL each of USP Vardenafil Related Compound D RS and USP Vardenafil Related Compound E RS, in Diluent. Sonicate to dissolve, if necessary.

System suitability solution: 0.22 mg/mL of USP Vardenafil Hydrochloride RS, and 0.001 mg/mL each of USP Vardenafil Related Compound D RS and USP Vardenafil Related Compound E RS, from System suitability stock solution, in Diluent

Standard stock solution: Use the Standard solution from the Assay.

Standard solution: 0.00022 mg/mL of USP Vardenafil Hydrochloride RS, equivalent to 0.0002 mg/mL of vardenafil, in Diluent from Standard stock solution

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times. The relative retention times for 7-methyl vardenafil, vardenafil, and vardenafil dimer are 0.6, 1.0, and 1.3, respectively.]

Suitability requirements

Resolution: NLT 2.0 between vardenafil related compound D and vardenafil related compound E, System suitability solution

Relative standard deviation: NMT 10.0% from 6 replicate injections, Standard solution

Signal-to-noise ratio: NLT 10, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual degradation product in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of each individual degradation product from the Sample solution

r_S = peak response of vardenafil from the Standard solution

C_S = concentration of USP Vardenafil Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of vardenafil in the Sample solution (mg/mL)

M_r1 = molecular weight of vardenafil, 488.61

M_r2 = molecular weight of anhydrous vardenafil hydrochloride, 525.07

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

^a 4-Ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulfonic acid.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature. Protect from light.

USP REFERENCE STANDARDS (11)

USP Vardenafil Hydrochloride RS

USP Vardenafil Related Compound D. RS

2-(2-Ethoxy-5-[(4-ethyl-4-oxido-1-piperazinyl) sulfonyl)phenyl)-5-methyl-7-propyl-imidazo[5,1-f][1,2,4]triazin-4(3H)-one.

C₂₃H₃₂N₆O₅S               504.61

USP Vardenafil Related Compound E RS

2-[2-Ethoxy-5-(1-piperazinylsulfonyl)phenyl]-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one.

C₂₂H₂₈N₆O₄S               460.55

USP Vardenafil System Suitability RS

Contains a mixture of the following two compounds: Vardenafil hydrochloride.

7-Methyl vardenafil (approximately 1%): (2-(2-Ethoxy-5-[(4-ethylpiperazin-1-yl) sulfonyl)phenyl)-5,7-dimethylimidazo[5,1-f][1,2,4]triazin-4(3H)-one).

C₂₁H₂₈N₆O₄S           460.55 _{▲(USP 1-Aug-2022)}