Diclofenac Sodium Extended-Release 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 

Diclofenac Sodium Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂). 

2 IDENTIFICATION 

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

B. The UV (190–400 nm) spectrum of the diclofenac peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

3.1 Procedure 

Solution A: 0.7708 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.3. Pass through a suitable lter of 0.2-µm pore size. 

Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1 

Diluent: Acetonitrile and water (50:50) 

Standard solution: 0.2 mg/mL of USP Diclofenac Sodium RS in Diluent 

Sample solution: Nominally 0.2 mg/mL of diclofenac sodium in Diluent prepared as follows. Transfer a suitable portion of diclofenac sodium to a suitable volumetric ask from NLT 20 nely powdered Tablets. Add Diluent equivalent to 70% of the ask volume. Dissolve with the aid of sonication for 25 min at 45° and ll with Diluent to volume. Pass the solution through a suitable lter of 0.22-µm pore size. [Note—Protect the Standard solution and Sample solution from light.] 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 280 nm. For Identication test B, use a photo-diode array detector. 

Column: 10-cm × 2.0-mm; 1.9-µm packing L1 

Column temperature: 35° 

Flow rate: 0.3 mL/min 

Injection volume: 1 µL 

System suitability 

Sample: Standard solution 

[Note—See Table 2 for relative retention times.] 

Suitability requirements 

Tailing factor: NMT 1.2 

Relative standard deviation: NMT 2.8% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of diclofenac from the Sample solution 

r_s = peak response of diclofenac from the Standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Standard solution (mg/mL) 

C_u = nominal concentration of diclofenac sodium in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Change to read: 

4.1 Dissolution 〈711〉 

Test 1 

Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL 

Apparatus 2: 50 rpm; use wire sinkers. 

Times: 1, 5, 10, 16, and 24 h 

Detector: UV 276 nm 

Standard solution: USP Diclofenac Sodium RS in Medium 

Analysis: Pass portions of the solution under test through a suitable lter. Dilute with Medium, if necessary, to a concentration similar to that of the Standard solution. 

Tolerances: See Table 2. 

Table 2 

The percentages of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved at the times specied conform to Acceptance Table 2 in 〈711〉. 

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

Medium, Apparatus 2, and Analysis: Proceed as directed for Dissolution Test 1. 

Times: 1, 2, 4, 6, and 10 h 

Tolerances: See Table 3. 

Table 3 

The percentages of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved at the times specied conform to Acceptance

Table 2 in 〈711〉. 

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3. 

Medium and Analysis: Proceed as directed for Dissolution Test 1. 

Apparatus 1: 100 rpm 

Times: 2, 4, 8, and 16 h 

Tolerances: See Table 4. 

Table 4 

The percentages of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved at the times specied conform to Acceptance Table 2 in 〈711〉. 

Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4. 

Medium and Analysis: Proceed as directed for Dissolution Test 1. 

Apparatus 1: 100 rpm 

Times: 2, 4, 8, and 16 h 

Tolerances: See Table 5. 

Table 5 

The percentages of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved at the times specied conform to Acceptance Table 2 in 〈711〉. 

Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5. 

Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL, deaerated 

Apparatus 2: 50 rpm; with sinkers (Dissolution 〈711〉, Figure 2a) 

Times: 1, 2, 4, 6, and 12 h 

Buffer: Dissolve 0.77 g of ammonium acetate in 1 L of water. Adjust with acetic acid to a pH of 5.3. 

Mobile phase: Acetonitrile and Buffer (45:55) 

Standard stock solution: 0.28 mg/mL of USP Diclofenac Sodium RS prepared as follows. Transfer a quantity of USP Diclofenac Sodium RS to an appropriate volumetric ask and dissolve in 5% of the ask volume of methanol. Dilute with Medium to volume. Standard solution: 0.112 mg/mL of USP Diclofenac Sodium RS from the Standard stock solution in Medium 

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size, discarding an appropriate volume of ltrate so that a consistent result can be obtained. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 280 nm 

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

Column temperature: 35° 

Flow rate: 1.2 mL/min 

Injection volume: 10 µL 

Run time: NLT 2 times the retention time of diclofenac 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the concentration (C ) of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) in the sample withdrawn from the vessel at each time point (i): 

Result = (r_u/r_s) × C_s

r_u = peak response of diclofenac from the Sample solution 

r_s = peak response of diclofenac from the Standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Standard solution (mg/mL) 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100 

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100 

Result₃ = ({C₃ × [V − (2 × V_S)]} + [(C₂ + C₁) × V_S]) × (1/L) × 100 

Result₄ = ({C₄ × [V − (3 × V_S)]} + [(C₃ + C₂ + C₁) × V_S)] × (1/L) × 100 

Result₅ = ({C₅ × [V − (4 × V_S)]} + [(C₄ + C₃ + C₂ + C₁) × V_S]) × (1/L) × 100 

C = concentration of diclofenac sodium in the portion of sample withdrawn at time point i (mg/mL) 

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

V = volume of the Sample solution withdrawn at each time point (mL) 

Tolerances: See Table 6. 

Table 6 

The percentages of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.(RB 1-Dec-2024) 

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Change to read: 

5.1 Organic Impurities 

Mobile phase and Diluent: Proceed as directed in the Assay. 

Standard solution: 0.001 mg/mL each of USP Diclofenac Sodium RS and USP Diclofenac Related Compound A RS in Diluent Sample solution: Nominally 1.0 mg/mL of diclofenac sodium in Diluent prepared as follows. Transfer a suitable portion of diclofenac sodium to a suitable volumetric ask from NLT 20 nely powdered Tablets. Add Diluent equivalent to 70% of the ask volume. Dissolve with the aid of sonication for 25 min at 45° and ll with Diluent to volume. Pass the solution through a suitable lter of 0.22-µm pore size. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 10-cm × 2.0-mm; 1.9-µm packing L1 

Column temperature: 35° 

Flow rate: 0.3 mL/min 

Injection volume: 1 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 5% 

Signal-to-noise ratio: NLT 10 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of diclofenac related compound A in the portion of Tablets taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of diclofenac related compound A from the Sample solution  

r_s = peak response of diclofenac related compound A from the Standard solution 

C_s = concentration of USP Diclofenac Related Compound A RS in the Standard solution (mg/mL) 

C_u = nominal concentration of diclofenac sodium in the Sample solution (mg/mL) 

Calculate the percentage of any other impurity in the portion of Tablets taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100 

r_u = peak response of each individual impurity from the Sample solution 

r_s = peak response of diclofenac from the Standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Standard solution (mg/mL) 

C_u = nominal concentration of diclofenac sodium in the Sample solution (mg/mL) 

Acceptance criteria: See Table 7. (RB 1-Dec-2024) Disregard any impurity peak less than 0.05%. 

Table 7 (RB 1-Dec-2024) 

a 1,3-Dihydro-2H-indol-2-one.

b Process-related impurities, not to be counted in total impurities. 

c 2-{2-[(2-Bromo-6-chlorophenyl)amino]phenyl}acetic acid. 

d {2-[(2,6-Dichlorophenyl)amino]phenyl}methanol. 

e 2-[(2,6-Dichlorophenyl)amino]benzaldehyde. 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage:

Preserve in well-closed containers. Store at controlled room temperature, and protect from light and moisture.

6.2 Labeling

When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used. • USP Reference Standards 〈11〉 

6.3 USP Diclofenac Sodium RS 

USP Diclofenac Related Compound A RS 

1-(2,6-Dichlorophenyl)indolin-2-one. 

C₁₄H₉Cl₂NO               278.13