Diclofenac Sodium Extended-Release Tablets
DEFINITION
Diclofenac Sodium Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diclofenac sodium (C14H10Cl2NNaO2).
IDENTIFICATION
• A.
The retention time of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• B. Thin-Layer Chromatographic Identification Test 
201
201
Standard solution:
2.0 mg/mL of USP Diclofenac Sodium RS in methanol. [Note—Shake by mechanical means for 10 min before makeup to final volume. ]
Sample solution:
Equivalent to 2.0 mg/mL of diclofenac sodium from a portion of the powder (NLT 10 Tablets) in methanol. [Note—Sonicate for 10 min, and shake by mechanical means for 10 min before makeup to final volume. Centrifuge this solution, and use the clear supernatant. ]
Developing solvent system:
Methanol, toluene, and glacial acetic acid (8:12:0.1)
ASSAY
• Procedure
[Note—Protect the Standard solution, System suitability solution, and Sample solution from light. ]
Diluent:
Methanol and water (7:3)
Buffer:
0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. Adjust with appropriate component to a pH of 2.5.
Mobile phase:
Methanol and Buffer (7:3)
Standard solution:
0.5 mg/mL of USP Diclofenac Sodium RS in Diluent
Resolution solution:
20 µg/mL of diethyl phthalate, 7.5 µg/mL of USP Diclofenac Related Compound A RS, and 0.75 mg/mL of USP Diclofenac Sodium RS in Diluent
Sample solution:
Powder NLT 20 Tablets, and transfer a weighed portion of the powder, equivalent to 100 mg of diclofenac sodium, to a 200-mL volumetric flask, and add 150 mL of Diluent. Heat on a steam bath for 3–5 min, and sonicate for 20 min. Cool to room temperature, and dilute with Diluent to volume. Place the flask in an ice bath for 45 min, shaking occasionally to precipitate out any undissolved waxy material. Pass a portion of the chilled solution through a filter of 0.45-µm or finer pore size. Allow the filtrate to reach room temperature before using.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; packing L7
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and Resolution solution
[Note—The relative retention times for diethyl phthalate, diclofenac related compound A, and diclofenac are 0.5, 0.6, and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.2 between the diethyl phthalate and diclofenac related compound A peaks, and NLT 3.8 between the diclofenac related compound A and diclofenac peaks, Resolution solution
Relative standard deviation:
NMT 2.0% for diclofenac, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C14H10Cl2NNaO2 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of diclofenac from the Sample solution |
| rS | = | = peak response of diclofenac from the Standard solution |
| CS | = | = concentration of USP Diclofenac Sodium RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of diclofenac sodium in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
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 filter. Dilute with Medium, if necessary, to a concentration similar to that of the Standard solution.
Tolerances:
The percentages of the labeled amount of C14H10Cl2NNaO2 dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 15%–35% |
| 5 | 45%–65% |
| 10 | 65%–85% |
| 16 | 75%–95% |
| 24 | NLT 80% |
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium, Apparatus, and Analysis:
Proceed as directed for Dissolution Test 1.
Times:
1, 2, 4, 6, and 10 h
Tolerances:
The percentages of the labeled amount of C14H10Cl2NNaO2 dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | NMT 28% |
| 2 | 20%–40% |
| 4 | 35%–60% |
| 6 | 50%–80% |
| 10 | NLT 65% |
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:
The percentages of the labeled amount of C14H10Cl2NNaO2 dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 2 | 22%–42% |
| 4 | 34%–61% |
| 8 | 52%–82% |
| 16 | NLT 73% |
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 Test 1.
Apparatus 1:
100 rpm
Times:
2, 4, 8, and 16 h
Tolerances:
The percentages of the labeled amount of C14H10Cl2NNaO2 dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 2 | 20%–40% |
| 4 | 35%–55% |
| 8 | 60%–85% |
| 16 | NLT 85% |
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Diluent, Buffer, Mobile phase, Resolution solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Standard stock solution:
0.8 mg/mL of USP Diclofenac Related Compound A RS in Diluent
Standard solution:
4 µg/mL of USP Diclofenac Related Compound A RS, made by diluting a measured volume of Standard stock solution with Diluent
System suitability solution:
0.5 mg/mL of USP Diclofenac Sodium RS in Diluent
System suitability
Samples:
Resolution solution and System suitability solution
[Note—The relative retention times for diethyl phthalate, diclofenac related compound A, and diclofenac are 0.5, 0.6, and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.2 between the diethyl phthalate and diclofenac related compound A peaks; and NLT 3.8 between the diclofenac related compound A and the diclofenac peaks, Resolution solution
Standard deviation:
NMT 2.0% for the diclofenac peak, System suitability solution
Analysis
Samples:
Sample solution and Standard solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) ×100
| rU | = | = peak response for any impurity from the Sample solution |
| rS | = | = peak response for USP Diclofenac Related Compound A RS from the Standard solution |
| CS | = | = concentration (mg/mL) of USP Diclofenac Related Compound A RS in the Standard solution |
| CU | = | = concentration (mg/mL) of diclofenac sodium in the Sample solution |
Acceptance criteria
Total impurities:
NMT 1.5%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature, and protect from light.
• 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
11
USP Diclofenac Sodium RS 
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USP Diclofenac Related Compound A RS
N-(2,6-Dichlorophenyl)indolin-2-one.
C14H9Cl2NO 278.14
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N-(2,6-Dichlorophenyl)indolin-2-one.
C14H9Cl2NO 278.14
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2883
Pharmacopeial Forum: Volume No. 35(5) Page 1130