Diclofenac Sodium Topical Solution

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 Topical Solution is a solution of Diclofenac Sodium in a suitable vehicle. It contains NLT 90.0% and NMT 110.0% of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂). 

2 IDENTIFICATION 

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

B. The UV spectrum 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 

Solution A: Phosphoric acid and water (0.62:1000) 

Solution B: 1.86 g of monobasic sodium phosphate dihydrate in 1000 mL of water 

Solution C: Solution A and Solution B (50:50) 

Mobile phase: Methanol and Solution C (70:30) 

Diluent: Methanol and water (70:30) 

Standard stock solution: 0.6 mg/mL of USP Diclofenac Sodium RS prepared as follows. Transfer a quantity of USP Diclofenac Sodium RS to a suitable volumetric ask, add 20% of the ask volume of methanol, sonicate to dissolve, and dilute with Diluent to volume. Standard solution: 0.06 mg/mL of USP Diclofenac Sodium RS from Standard stock solution diluted with Diluent 

Sample solution: Nominally 0.06 mg/mL of diclofenac sodium prepared as follows. Transfer a quantity of Topical Solution to a suitable volumetric ask, add 20% of the ask volume of methanol, sonicate for about 10 min, and dilute with Diluent to volume. Pass a portion of the solution through a suitable lter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm. For Identication B, use a diode array detector in the range of 200–400 nm. 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Column temperature: 30° 

Flow rate: 1 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 percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) in the portion of Topical Solution 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 IMPURITIES 

4.1 Organic Impurities 

Solution A, Solution B, Solution C, and Diluent: Prepare as directed in the Assay. 

Mobile phase A: Use Solution C. 

Mobile phase B: Methanol and acetonitrile (90:10) 

Mobile phase: See Table 1. 

Table 1 

Standard stock solution: 0.3 mg/mL of USP Diclofenac Sodium RS prepared as follows. Transfer a quantity of USP Diclofenac Sodium RS to a suitable volumetric ask, add 20% of the ask volume of methanol, sonicate to dissolve, and dilute with Diluent to volume. Standard solution: 0.003 mg/mL of USP Diclofenac Sodium RS from Standard stock solution diluted with Diluent 

Sensitivity solution: 0.3 µg/mL of USP Diclofenac Sodium RS in Diluent from Standard solution 

Sample solution: Nominally 0.6 mg/mL of diclofenac sodium prepared as follows. Transfer a suitable quantity of the Topical Solution to a suitable volumetric ask, add 20% of the ask volume of methanol, and sonicate to disperse. Add 50% of the ask volume of Diluent, sonicate for about 15 min, and dilute with Diluent to volume. Pass a portion of the solution through a suitable lter of 0.45-µm pore size. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Column temperature: 45° 

Flow rate: 1.2 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: Standard solution and Sensitivity solution 

Suitability requirements 

Relative standard deviation: NMT 5.0%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each specied and any unspecied degradation product in the portion of Topical Solution taken: 

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100 

r_u = peak response of each specied or unspecied degradation product 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) 

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. 

Table 2 

a 2-[(2,6-Dichlorophenyl)amino]phenyl-2-oxoacetic acid.

b 1-(2,6-Dichlorophenyl)indolin-2-one. 

5 SPECIFIC TESTS 

5.1 Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉:

The total aerobic microbial count is NMT 102 cfu/mL, and the total combined yeasts and molds count is NMT 10 cfu/mL. It meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa. 

Delete the following: 

5.2 pH 〈791〉: 8.0–10.0▲ (RB 1-Apr-2021) 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage:

Store at controlled room temperature. 

6.2 USP Reference Standards 〈11〉 

USP Diclofenac Sodium RS