Diclofenac Potassium for Oral 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 

To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb diclofenac-na-for-os-20220429. 

Diclofenac Potassium for Oral Solution contains NLT 95.0% and NMT 105.0% of the labeled amount of diclofenac potassium (C₁₄H₁₀Cl₂NKO₂).  

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: Dissolve 1.56 g of monobasic sodium phosphate dihydrate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.5.

Solution B: Dissolve 6.8 g of monobasic potassium phosphate and 0.88 g of sodium hydroxide in 1000 mL of water. Adjust with 1 N sodium hydroxide to a pH of 6.8. 

Mobile phase: Acetonitrile and Solution A (40:60) 

Diluent: Methanol and Solution B (10:90) 

Standard solution: 0.2 mg/mL of USP Diclofenac Potassium RS in Diluent. Sonicate to dissolve, if needed. 

Sample stock solution: Nominally 0.5 mg/mL of diclofenac potassium prepared as follows. Transfer a portion of nely powdered contents of NLT 5 packets of Diclofenac Potassium for Oral Solution, equivalent to 100 mg of diclofenac potassium, to a 200-mL volumetric ask. Add 140 mL of Diluent, and sonicate for about 10 min. Dilute with Diluent to volume. Centrifuge a portion of the solution. [Note—A centrifuge speed of 3500 rpm for 10 min may be suitable.] 

Sample solution: Nominally 0.2 mg/mL of diclofenac potassium in Diluent from the Sample stock solution. Pass 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 × 15-cm; 5-µm packing L1 

Column temperature: 40° 

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

Run time: NLT 1.4 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 potassium (C₁₄H₁₀Cl₂NKO₂) in the portion of Diclofenac Potassium for Oral 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 Potassium RS in the Standard solution (mg/mL) 

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

4 PERFORMANCE TESTS 

4.1 Dissolution 〈711〉 

Medium: pH 6.8 phosphate buffer (19 g/L of trisodium phosphate dodecahydrate in 0.1 N hydrochloric acid, adjusted with 1 N sodium hydroxide to a pH of 6.8); 400 mL 

Apparatus 2: 75 rpm 

Time: 5 min 

Solution A and Chromatographic system: Proceed as directed in the Assay. 

Mobile phase: Acetonitrile and Solution A (50:50) 

Standard solution: 0.125 mg/mL of USP Diclofenac Potassium RS prepared as follows. Transfer a quantity of USP Diclofenac Potassium RS to a suitable volumetric ask. Add methanol to 5% of the ask volume and sonicate to dissolve. Dilute with Medium to volume. Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-um pore size. 

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 potassium (C₁₄H₁₀Cl₂NKO₂) dissolved: 

Result = (r_u/r_s) × C_s × V × (1/L) × 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 Potassium RS in the Standard solution (mg/mL) 

V = volume of Medium, 400 mL 

L = label claim of diclofenac potassium (mg/packet) 

Tolerances: NLT 80% (Q) of the labeled amount of diclofenac potassium (C₁₄H₁₀Cl₂NKO₂) is dissolved. 

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

5 IMPURITIES 

5.1 Organic Impurities 

Solution A: Prepare as directed in the Assay. 

Solution B: Dissolve 6.8 g of monobasic potassium phosphate in 1000 mL of water. Adjust with 1 N sodium hydroxide to a pH of 6.8. Mobile phase: Methanol and Solution A (66:34) 

Diluent: Methanol and Solution B (10:90) 

Sensitivity solution: 0.5 µg/mL of USP Diclofenac Potassium RS in Diluent 

Standard stock solution: 0.15 mg/mL of USP Diclofenac Related Compound A RS in methanol 

Standard solution: 1 µg/mL of USP Diclofenac Related Compound A RS and 2.5 µg/mL of USP Diclofenac Potassium RS, prepared as follows. Transfer a volume of Standard stock solution and a quantity of USP Diclofenac Potassium RS to a suitable volumetric ask, and add Diluent to dissolve. Sonicate if needed. Dilute with Diluent to volume. 

Sample solution: Nominally 500 µg/mL of diclofenac potassium in Diluent, prepared as follows. Transfer a portion of nely powdered contents of NLT 5 packets of Diclofenac Potassium for Oral Solution, equivalent to 50 mg of diclofenac potassium, to a 100-mL volumetric ask. Add 70 mL of Diluent, and sonicate for 10 min. Dilute with Diluent to volume. Pass a portion of the solution through a suitable lter of 0.45-µm pore size, and discard the rst 5 mL of the ltrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

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

Flow rate: 1 mL/min 

Injection volume: 25 µL 

Run time: NLT 2.2 times the retention time of diclofenac 

System suitability 

Samples: Sensitivity solution and Standard solution 

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

Suitability requirements 

Relative standard deviation: NMT 5.0% for diclofenac and diclofenac related compound A, Standard solution Signal-to-noise ratio: NLT 10, Sensitivity solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of diclofenac related compound A in the portion of Diclofenac Potassium for Oral Solution 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 (µg/mL) 

C_u = nominal concentration of diclofenac potassium in the Sample solution (µg/mL) 

Calculate the percentage of any unspecied degradation product in the portion of Diclofenac Potassium for Oral Solution taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100 

r_u = peak response of any unspecied degradation product from the Sample solution 

r_s = peak response of diclofenac from the Standard solution 

C_s = concentration of USP Diclofenac Potassium RS in the Standard solution (µg/mL) 

C_u = nominal concentration of diclofenac potassium in the Sample solution (µg/mL) 

Acceptance criteria: See Table 1. 

Table 1 

6 SPECIFIC TESTS 

6.1 Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉

The total aerobic microbial count is NMT 103 cfu/g. The total combined yeasts and molds count is NMT 102 cfu/g. It meets the requirements of the test for absence of Escherichia coli.

Change to read: 

6.2 pH 〈791〉 

Sample: Dissolve the contents of a unit dosage of Diclofenac Potassium for Oral Solution in 30 mL of water.

Acceptance criteria: 7.0–11.5 (RB 31-Mar-2022) 

7 ADDITIONAL REQUIREMENTS 

7.1 Packaging and Storage: Store at controlled room temperature. 

7.2 USP Reference Standards 〈11〉 

USP Diclofenac Potassium RS 

USP Diclofenac Related Compound A RS 

1-(2,6-Dichlorophenyl)indolin-2-one. 

C₁₄H₉Cl₂NO           278.13