Printed on: Tue Jul 26 2022, 11:56:19 PM(EST) Status: Currently Official on 27-Jul-2022 DocId: GUID-20F3DB54-53C6-47F8-AC5A-65BDCA0173AA_2_en-US

Printed by: Rock Pharma Official Date: Official as of 01-May-2016 Document Type: USP @2022 USPC
DOI Ref: sd841 DOI: https://doi.org/10.31003/USPNF_M24972_02_01
1

Calculate the percentage of the labeled amount of

Diclofenac Sodium Extended-Release diclofenac sodium (C14H10Cl2NNaO2) in the portion of
Tablets Tablets taken:
DEFINITION Result = (rU/rS) × (CS/CU) × 100
Diclofenac Sodium Extended-Release Tablets contain NLT
90.0% and NMT 110.0% of the labeled amount of diclofenac rU = peak response of diclofenac from the Sample
sodium (C14H10Cl2NNaO2). solution
rS = peak response of diclofenac from the Standard
IDENTIFICATION solution
• A. The retention time of the diclofenac peak of the Sample CS = concentration of USP Diclofenac Sodium RS in the
solution corresponds to that of the Standard solution, as Standard solution (mg/mL)
obtained in the Assay. CU = nominal concentration of diclofenac sodium in
• B. The UV (190–400 nm) spectrum of the diclofenac peak the Sample solution (mg/mL)
of the Sample solution corresponds to that of the Standard
solution, as obtained in the Assay. Acceptance criteria: 90.0%–110.0%
ASSAY PERFORMANCE TESTS
• PROCEDURE • DISSOLUTION á711ñ
Solution A: 0.7708 g/L of ammonium acetate in water. Test 1
Adjust with acetic acid to a pH of 5.3. Pass through a Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL
suitable filter of 0.2-µm pore size. Apparatus 2: 50 rpm; use wire sinkers.
Solution B: Acetonitrile Times: 1, 5, 10, 16, and 24 h

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Mobile phase: See Table 1. Detector: UV 276 nm
Standard solution: USP Diclofenac Sodium RS in Medium
Table 1 Analysis: Pass portions of the solution under test through a
Time Solution A Solution B suitable filter. Dilute with Medium, if necessary, to a
(min) (%) (%) ci concentration similar to that of the Standard solution.
0.00 70 30 Tolerances: See Table 2.
0.50 70 30 Table 2
8.50 5 95 Time Amount
(h) Dissolved
10.00 5 95
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1 15%–35%
10.01 70 30
5 45%–65%
14.00 70 30
10 65%–85%

Diluent: Acetonitrile and water (50:50) 16 75%–95%

Standard solution: 0.2 mg/mL of USP Diclofenac
O

24 NLT 80%
Sodium RS in Diluent
Sample solution: Nominally 0.2 mg/mL of diclofenac
sodium in Diluent prepared as follows. Transfer a suitable The percentages of the labeled amount of diclofenac
portion of diclofenac sodium to a suitable volumetric flask sodium (C14H10Cl2NNaO2) dissolved at the times
from NLT 20 finely powdered Tablets. Add Diluent specified conform to Acceptance Table 2 in á711ñ.
equivalent to 70% of the flask volume. Dissolve with the aid Test 2: If the product complies with this test, the labeling
of sonication for 25 min at 45° and fill with Diluent to indicates that it meets USP Dissolution Test 2.
volume. Pass the solution through a suitable filter of Medium, Apparatus 2, and Analysis: Proceed as
0.22-µm pore size. directed for Dissolution Test 1.
[NOTE—Protect the Standard solution and Sample solution Times: 1, 2, 4, 6, and 10 h
from light.] Tolerances: See Table 3.
Chromatographic system
(See Chromatography á621ñ, System Suitability.) Table 3
Mode: LC Time Amount
Detector: UV 280 nm. For Identification test B, use a (h) Dissolved
photo-diode array detector. 1 NMT 28%
Column: 10-cm × 2.0-mm; 1.9-µm packing L1
Column temperature: 35° 2 20%–40%
Flow rate: 0.3 mL/min 4 35%–60%
Injection volume: 1 µL
System suitability 6 50%–80%
Sample: Standard solution 10 NLT 65%
[NOTE—See Table 2 for relative retention times.]
Suitability requirements
Tailing factor: NMT 1.2 The percentages of the labeled amount of diclofenac
Relative standard deviation: NMT 2.8% sodium (C14H10Cl2NNaO2) dissolved at the times
Analysis specified conform to Acceptance Table 2 in á711ñ.
Samples: Standard solution and Sample solution Test 3: If the product complies with this test, the labeling
indicates that it meets USP Dissolution Test 3.

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Printed on: Tue Jul 26 2022, 11:56:19 PM(EST) Status: Currently Official on 27-Jul-2022 DocId: GUID-20F3DB54-53C6-47F8-AC5A-65BDCA0173AA_2_en-US
Printed by: Rock Pharma Official Date: Official as of 01-May-2016 Document Type: USP @2022 USPC
DOI Ref: sd841 DOI: https://doi.org/10.31003/USPNF_M24972_02_01
2

Medium and Analysis: Proceed as directed for Dissolution Suitability requirements

Test 1. Relative standard deviation: NMT 5%
Apparatus 1: 100 rpm Signal-to-noise ratio: NLT 10
Times: 2, 4, 8, and 16 h Analysis
Tolerances: See Table 4. Samples: Standard solution and Sample solution
Calculate the percentage of diclofenac related compound A
Table 4 in the portion of Tablets taken:
Time Amount
(h) Dissolved Result = (rU/rS) × (CS/CU) × 100
2 22%–42% rU = peak response of diclofenac related compound A
4 34%–61% from the Sample solution
rS = peak response of diclofenac related compound A
8 52%–82% from the Standard solution
16 NLT 73% CS = concentration of USP Diclofenac Related
Compound A RS in the Standard solution
The percentages of the labeled amount of diclofenac (mg/mL)
sodium (C14H10Cl2NNaO2) dissolved at the times CU = nominal concentration of diclofenac sodium in
the Sample solution (mg/mL)
specified conform to Acceptance Table 2 in á711ñ.
Test 4: If the product complies with this test, the labeling Calculate the percentage of any other impurity in the
indicates that it meets USP Dissolution Test 4. portion of Tablets taken:
Medium and Analysis: Proceed as directed for Dissolution

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Test 1. Result = (rU/rS) × (CS/CU) × 100
Apparatus 1: 100 rpm
Times: 2, 4, 8, and 16 h rU = peak response of each individual impurity from
Tolerances: See Table 5. the Sample solution
ci rS = peak response of diclofenac from the Standard
Table 5 solution
Time Amount CS = concentration of USP Diclofenac Sodium RS in the
(h) Dissolved Standard solution (mg/mL)
2 20%–40% CU = nominal concentration of diclofenac sodium in
the Sample solution (mg/mL)
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4 35%–55%

8 60%–85% Acceptance criteria: See Table 6. Disregard any impurity

peak less than 0.05%.
16 NLT 85%
Table 6
The percentages of the labeled amount of diclofenac Relative Acceptance
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sodium (C14H10Cl2NNaO2) dissolved at the times Retention Criteria,

Name Time NMT (%)
specified conform to Acceptance Table 2 in á711ñ.
• UNIFORMITY OF DOSAGE UNITS á905ñ: Meet the Oxindole a, b
0.4 —
requirements
Diclofenac 1.0 —
IMPURITIES Diclofenac related compound D (diclofe-
• ORGANIC IMPURITIES nac bromo analog)c, b 1.04
—
Mobile phase and Diluent: Proceed as directed in the
Assay. Diclofenac related compound A 1.48 0.5
Standard solution: 0.001 mg/mL each of USP Diclofenac Diclofenac alcohol analog d, b
1.55 —
Sodium RS and USP Diclofenac Related Compound A RS in
Diluent Diclofenac benzaldehyde analog e, b
1.81 —
Sample solution: Nominally 1.0 mg/mL of diclofenac Any individual unspecified
—
sodium in Diluent prepared as follows. Transfer a suitable impurity 0.5
portion of diclofenac sodium to a suitable volumetric flask
Total impurities b — 1.5
from NLT 20 finely powdered Tablets. Add Diluent
equivalent to 70% of the flask volume. Dissolve with the aid a 1,3-Dihydro-2H-indol-2-one.
of sonication for 25 min at 45° and fill with Diluent to b Process-related impurities, not to be counted in total impurities.
volume. Pass the solution through a suitable filter of c 2-{2-[(2-Bromo-6-chlorophenyl)amino]phenyl}acetic acid.
0.22-µm pore size. d {2-[(2,6-Dichlorophenyl)amino]phenyl}methanol.
Chromatographic system e 2-[(2,6-Dichlorophenyl)amino]benzaldehyde.
(See Chromatography á621ñ, System Suitability.)
Mode: LC ADDITIONAL REQUIREMENTS
Detector: UV 254 nm • PACKAGING AND STORAGE: Preserve in well-closed
Column: 10-cm × 2.0-mm; 1.9-µm packing L1 containers. Store at controlled room temperature, and
Column temperature: 35° protect from light and moisture.
Flow rate: 0.3 mL/min • LABELING: When more than one Dissolution test is given, the
Injection volume: 1 µL labeling states the test used only if Test 1 is not used.
System suitability • USP REFERENCE STANDARDS á11ñ
Sample: Standard solution USP Diclofenac Sodium RS

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Printed on: Tue Jul 26 2022, 11:56:19 PM(EST) Status: Currently Official on 27-Jul-2022 DocId: GUID-20F3DB54-53C6-47F8-AC5A-65BDCA0173AA_2_en-US
Printed by: Rock Pharma Official Date: Official as of 01-May-2016 Document Type: USP @2022 USPC
DOI Ref: sd841 DOI: https://doi.org/10.31003/USPNF_M24972_02_01
3

USP Diclofenac Related Compound A RS

1-(2,6-Dichlorophenyl)indolin-2-one.
C14H9Cl2NO 278.13

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ci
ffi
O

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