Tadalafil 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

Tadalafi Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of Tadalafil (C₂₂H₁₉N₃O₄).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy 197D or 197K (CN 1-May-2020)

Standard: Add 10 mg of USP tadalafil

RS to 15 mL of water. Shake for 20 min, centrifuge for 10 min, and discard the supernatant. Suspend the precipitate in 8 mL of ethyl acetate, and shake for 5 min. Centrifuge for 10 min, and collect the supernatant. Dry the supernatant under a stream of nitrogen. The supernatant may be heated up to 70° to aid evaporation of the ethyl acetate. [Note—Ethyl acetate must be completely removed to prevent interference in the spectrum.]

Sample: Transfer a quantity of Tablets, equivalent to 10–20 mg of tadalafil, into a suitable container. Add 15 mL of water, and shake for 10 min, or until the Tablets are completely dispersed. Centrifuge for 10 min, and discard the supernatant. Suspend the precipitate in 8 mL of ethyl acetate, and shake for 5 min. Centrifuge for 10 min, and collect the supernatant. Dry the supernatant under a stream of nitrogen. The supernatant may be heated up to 70° to aid evaporation of the ethyl acetate. [Note—Ethyl acetate must be completely removed to prevent interference in the spectrum.]

Acceptance criteria: Meet the requirements over the range from 1700–400 cm−1

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

3.1 Procedure

Mobile phase: Acetonitrile, water, and trifluoroacetic acid (35:65: 0.1)

Diluent: Acetonitrile and water (1:1)

Standard solution: 0.25 mg/mL of USP tadalafil

RS in Diluent

System suitability solution: To partially convert tadalafil to the 6R,12aS diastereomer, transfer 25 mL of the Standard solution into a suitable container. Add 0.25 mL of 5 N sodium hydroxide, mix well, and let stand for 30 min. Neutralize the solution to pH 7 by drop-wise addition of trifluoroacetic acid. [Note—This solution is stable for 1 month when stored in a refrigerator.]

Sample solution: Place NLT 20 Tablets into an appropriate size volumetric flask. Fill the flask about halfway with Diluent, and shake the mixture for about 15 min to disintegrate the Tablets. If any large fragments remain, sonicate the solution for 2 min or until fragments are dispersed. Dilute with Diluent to volume, and mix. Allow the solution to stand for at least 1 h to further aid Tablet dissolution. If necessary, shake the solution and perform a secondary dilution to obtain a final nominal concentration of 0.25 mg/mL. Centrifuge or filter the solution.

[Note—The initial concentration before a secondary dilution step should not exceed 6 mg/mL.]

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm × 15-cm; 3.5-μm packing L7

Column temperature: 35°

Flow rate: 1.0 mL/min

Injection volume: 10 μL

3.3 System suitability

Samples: Standard solution and System suitability solution

[Note—The relative retention times for tadalafil and the 6R,12aS diastereomer of tadalafil are about 1.0 and 1.2, respectively.]

3.4 Suitability requirements

Resolution: NLT 3 between tadalafil and the 6R,12aS diastereomer peak, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tadalafil (C₂₂H₁₉N₃O₄) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.5% sodium dodecyl sulfate; 1000 mL

Apparatus 2: 50 rpm, use suitable sinkers if necessary

Times: 10 and 30 min

Mobile phase: Methanol and water (50:50)

Standard stock solution: 0.25 mg/mL of USP tadalafil

RS in acetonitrile and water (1:1)

Standard solution: 0.0075 mg/mL of USP tadalafil

RS in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 5.0-cm; 3.5-μm packing L7

Column temperature: 40°

Flow rate: 2.0 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tadalafil (C₂₂H₁₉N₃O₄) dissolved at each time point (Q):

Q₁₀ = (r_U /r_S ) × (C_S /L) × V × 100

Q₃₀ = (Q₁₀ × v/V) + [(r_U /r_S ) × (C_S /L) × (V − v) × 100]

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 1000 mL

v = volume of the sample withdrawn at initial time point (mL)

Tolerances: NLT 40% (Q) of the labeled amount of tadalafil is dissolved in 10 min and NLT 80% (Q) of the labeled amount of tadalafil is dissolved in 30 min.

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

Medium, Mobile phase, Standard stock solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in Test 1.

Apparatus 2: 50 rpm, use suitable sinkers if necessary

Time: 15 min

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tadalafil (C₂₂H₁₉N₃O₄ ) dissolved:

Result = (r_U /r_S ) × C_S × V × (1/L) × 100

r_U= peak response of tadalafil from the Sample solution

r_S = peak response of tadalafil from the Standard solution

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

V = volume of Medium, 1000 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of tadalafil (C₂₂H₁₉N₃O₄) is dissolved.

Uniformity of Dosage Units 〈905〉

Procedure for content uniformity

Diluent: Acetonitrile and water (1:1)

Standard solution: 0.1–0.2 mg/mL of USP tadalafil RS in Diluent

Sample solution: Add 1 Tablet to a suitable volumetric flask to prepare a solution having a nominal concentration of 0.1–0.2 mg/mL of tadalafil. Add a volume of Diluent equivalent to 50% of the volume of the flask, and mechanically shake for 15 min. Dilute with Diluent to volume, and pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Cell: 0.1 cm

Analytical wavelength: Absorption maximum at about 285 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tadalafil (C₂₂H₁₉N₃O₄) in the Tablet taken:

Result = (A_U/A_S) × (C_S /C_U ) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

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

Acceptance criteria: Meet the requirements for coated Tablets

5 IMPURITIES

Organic Impurities

Mobile phase, Diluent, Standard solution, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.25 μg/mL of USP tadalafil RS in Diluent from the Standard solution

System suitability

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

[Note—The relative retention times for tadalafil and the 6R,12aS diastereomer of tadalafil are about 1.0 and 1.2, respectively.]

Suitability requirements

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Resolution: NLT 3 between tadalafil and the 6R,12aS diastereomer peak, System suitability solution

Signal-to-noise ratio: NLT 20, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U/r_T ) × 100

r_U = peak response of each impurity from the Sample solution

r_T = sum of the peak responses from the Sample solution

Acceptance criteria

Individual impurities: NMT 0.2%

Total impurities: NMT 0.3%

Reporting level for impurities: 0.05%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP tadalafil RS