Diclofenac Sodium Delayed-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 Delayed-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 50% of the ask volume. Dissolve with sonication for 20 min at 40° 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 1.0% 

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 

4.1 Dissolution 〈711〉 

Proceed as directed in Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method B to determine the amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved. 

Acid stage 

Medium: 0.1 N hydrochloric acid; 900 mL 

Apparatus 2: 50 rpm, paddles constructed of (or coated with) polytef being used 

Time: 2 h 

Detector: UV, maxima at about 276 nm 

Standard solution: Transfer 68 mg of USP Diclofenac Sodium RS to a 100-mL volumetric ask, add 10.0 mL of 0.1 N sodium hydroxide, and dilute with water to volume. Transfer 2.0 mL of this solution to a second 100-mL volumetric ask, dilute with a mixture of 0.1 N hydrochloric acid and 5 N sodium hydroxide (900:20) to volume, and mix. This Standard solution contains 13.6 µg/mL of USP Diclofenac Sodium RS. 

Sample solution: At the end of 2 h, remove each Tablet, or the major portion thereof if the Tablet is not intact, from the individual vessels, and subject them to the test under Buffer stage. To the 0.1 N hydrochloric acid remaining in each vessel, add 20.0 mL of 5 N sodium hydroxide, and stir for 5 min. 

Buffer stage 

Medium: pH 6.8 phosphate buffer; 900 mL 

Apparatus 2: 50 rpm 

Time: 45 min 

Detector: UV, maxima at about 276 nm 

Solution A: 76 mg/mL of tribasic sodium phosphate 

pH 6.8 phosphate buffer: Solution A and 0.1 N hydrochloric acid (1:3), adjusted with 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.05, if necessary 

Standard solution: Transfer 68 mg of USP Diclofenac Sodium RS to a 100-mL volumetric ask. Add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 3.0 mL of this solution to a 100-mL volumetric ask, dilute with Buffer stage Medium to volume, and mix. The nal concentration is about 0.0204 mg/mL of diclofenac sodium. 

Sample solution: Sample per Dissolution 〈711〉. Dilute with Medium to a concentration similar to that of the Standard solution. Tolerances: NLT 75% (Q) of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) is dissolved. 

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

5 IMPURITIES 

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 50% of the ask volume. Dissolve with sonication for 20 min at 40° and ll with Diluent to volume. Pass the solution through a suitable lter of 0.22-µm pore size. Chromatographic system: Proceed as directed in the Assay, except for the Detector. 

Detector: UV 254 nm 

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 2. Disregard any impurity peak less than 0.05%. 

Table 2 

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 tight, light-resistant containers. Store at controlled room temperature. Protect from moisture.

6.2 USP Reference Standards 〈11〉 

USP Diclofenac Sodium RS 

USP Diclofenac Related Compound A RS 

1-(2,6-Dichlorophenyl)indolin-2-one. 

C₁₄H₉Cl₂NO           278.13