Sildenafil 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 

Sildenafil Tablets contain Sildenafil citrate equivalent to NLT 90% and NMT 110% of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S).

2 IDENTIFICATION 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

Solution A: Ammonium hydroxide and water (10:90) 

Standard solution: 1.4 mg/mL of USP Sildenafil Citrate RS in Solution A 

Sample solution: Grind 1 Tablet and add a sufficient amount of Solution A to obtain nominally 1 mg/mL of Sildenafil. Sonicate for 2 min, shake well, and centrifuge. Use the supernatant. 

Analysis: For each of the Standard solution and the Sample solution, prewash a 6-cc C18 solid phase extraction cartridge with 10 mL of methanol followed by 10 mL of Solution A, discarding both washings. Apply 5 mL each of the Standard solution and the Sample solution to separate prewashed cartridges and draw each solution through the cartridge. Wash each cartridge with 10 mL of water and allow the cartridge to dry under vacuum. Elute the Sildenafil from each cartridge with 5 mL of methanol, collecting the eluant in a suitable container. Add about 200 mg of potassium bromide to each container, mix well, and evaporate to dryness. To about 70 mg of each dried mixture, add about 140 mg of potassium bromide and mix. 

Acceptance criteria: Meet the requirements 

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 

Buffer: Dilute 7 mL of triethylamine with water to 1 L. Adjust with phosphoric acid to a pH of 3.0. 

Mobile phase: Buffer, methanol, and acetonitrile (58:25:17) 

Diluent: Acetonitrile and water (90:10) 

Standard solution: 0.028 mg/mL of USP Sildenafil Citrate RS in Mobile phase 

Sample stock solution: Disperse 1 Tablet in at least 5 mL of Diluent with the aid of sonication. Once the Tablet is fully dispersed, dilute with Mobile phase to 250.0 mL while swirling. Centrifuge and use the supernatant. 

Sample solution: Nominally 0.02 mg/mL of Sildenafil prepared by diluting a suitable portion of the Sample stock solution with Mobile phase Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 290 nm 

Column: 3.9-mm × 15-cm; 5-µm packing L1 

Column temperature: 30° 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

Run time: NLT 1.5 times the retention time of Sildenafil 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 1.3 

Relative standard deviation: NMT 3.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S) 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 Sildenafil from the Sample solution 

r_S = peak response of Sildenafil from the Standard solution 

C_S = concentration of USP Sildenafil Citrate RS in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of Sildenafil, 474.58  

M_r2 = molecular weight of Sildenafil citrate, 666.70 

Acceptance criteria: 90%–110% 

4 PERFORMANCE TESTS 

Change to read: 

Dissolution 〈711〉 

Test 1  

Medium: 0.01 N hydrochloric acid; 900 mL 

Apparatus 1: 100 rpm Time: 15 min 

Standard solution: 0.03 mg/mL of USP Sildenafil Citrate RS in Medium 

Sample solution: A filtered portion of the solution under test, suitably diluted with Medium, if necessary 

Instrumental conditions 

Mode: UV-Vis 

Analytical wavelength: Maximum at about 290 nm 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S) dissolved: 

Result = (A_U/A_S) × C_S × D × V × (1/L) × (M_r1 /M_r2) × 100 

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution 

C_S = concentration of USP Sildenafil Citrate RS in the Standard solution (mg/mL) 

D = dilution factor for the Sample solution, if needed 

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

M_r1 = molecular weight of Sildenafil, 474.58  

M_r2 = molecular weight of Sildenafil citrate, 666.70

Tolerances: NLT 80% (Q) of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S) is dissolved. 

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. 

Medium: 0.1 N hydrochloric acid; 500 mL 

Apparatus 1: 100 rpm 

Time: 15 min 

Standard solution: 0.03 mg/mL of USP Sildenafil Citrate RS in Medium. Sonicate to dissolve, if necessary. Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Dilute with Medium to a concentration similar to that of the Standard solution. Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: UV 

Analytical wavelength: 290 nm 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S dissolved: 

Result = (A_U/A_S) × C_S × D × V × (1/L) × (M_r1 /M_r2) × 100 

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution 

C_S = concentration of USP Sildenafil Citrate RS in the Standard solution (mg/mL) 

D = dilution factor for the Sample solution, if needed 

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

M_r1 = molecular weight of Sildenafil, 474.58  

M_r2 = molecular weight of Sildenafil citrate, 666.70 

Tolerances: NLT 80% (Q) of the labeled amount of Sildenafil (C₂₂H₃₀N₆O₄S) is dissolved.  

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Organic Impurities 

Buffer, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay, except for Run time. Run time: NLT 3 times the retention time of Sildenafil 

System suitability solution: A mixture of Sildenafil and Sildenafil N-oxide in Mobile phase, prepared as follows. Dissolve 70 mg of USP Sildenafil Citrate RS in 1 mL of a solution of Hydrogen peroxide and formic acid (2:1), allow to stand for NMT 10 min, and then dilute with Mobile phase to 250.0 mL. 

Standard solution: 0.0014 mg/mL of USP Sildenafil Citrate RS in Mobile phase 

Sensitivity solution: 0.00035 mg/mL of USP Sildenafil Citrate RS in Mobile phase from the Standard solution 

Sample stock solution: Transfer 5 Tablets to a 250-mL volumetric ask and disperse in 25 mL of Diluent with the aid of sonication. Dilute with Mobile phase to volume. Sonicate, if necessary. Centrifuge and use the supernatant. 

Sample solution: Nominally 0.5 mg/mL of Sildenafil prepared by diluting a suitable portion of the Sample stock solution with Mobile phase System suitability 

Samples: System suitability solution, Standard solution, and Sensitivity solution 

[Note—See Table 1 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 2.6 between Sildenafil N-oxide and Sildenafil, System suitability solution 

Tailing factor: NMT 1.3, Standard solution 

Relative standard deviation: NMT 3.0%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of any 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 any individual degradation product from the Sample solution

r_S = peak response of Sildenafil from the Standard solution 

C_S = concentration of USP Sildenafil Citrate RS in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of Sildenafil, 474.58  

M_r2 = molecular weight of Sildenafil citrate, 666.70 

Acceptance criteria: See Table 1. Disregard any peak less than 0.05%. 

Table 1 

a 1-{[3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl}-4-methylpiperazine N4-oxide. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature. 

Add the following: 

Labeling: The labeling states the Dissolution test used only if Test 1 is not used.  

USP Reference Standards 〈11〉 

USP Sildenafil Citrate RS