Diclofenac Sodium Delayed-Release Tablets
DEFINITION
Diclofenac Sodium Delayed-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 diclofenac peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
•  B. Identification Tests—General, Sodium 191: It meets the requirements of the flame test.
ASSAY
•  Procedure
Solution A:  Mix equal volumes of 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. If necessary, adjust with additional portions of the appropriate component to a pH of 2.5 ± 0.2.
Mobile phase:  Methanol and Solution A (7:3)
[Note—Increasing the proportion of buffer increases resolution. ]
Diluent:  Methanol and water (7:3)
System suitability 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
Standard solution:  0.75 mg/mL of USP Diclofenac Sodium RS in Diluent
Sample solution:  Transfer 20 Tablets to a volumetric flask of such capacity that when filled to volume, a concentration of 0.75 mg/mL of diclofenac sodium is obtained. Add Diluent to about 70% of the capacity of the flask, and shake by mechanical means for NLT 30 min to disintegrate the Tablets. Cool to room temperature, and dilute with Diluent to volume. Pass a portion of the solution through a filter of 0.5-µm or finer pore size, and use the filtrate as the Sample solution.
Chromatographic system 
Mode:  LC
Detector:  UV 254 nm
Column:  4.6-mm × 25-cm; packing L7 (end-capped)
Flow rate:  1 mL/min
Injection size:  10 µL
System suitability 
Samples:  System suitability solution and Standard 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; NLT 6.5 between the diclofenac related compound A and diclofenac peaks, System suitability solution
Relative standard deviation:  NMT 2.0%, 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: Proceed as directed for Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method B to determine the amount of 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 flask, 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 flask, 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 flask. 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 flask, dilute with Buffer stage Medium to volume, and mix. The final 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 C14H10Cl2NNaO2 is dissolved.
•  Uniformity of Dosage Units 905: Meet the requirements
IMPURITIES
Organic Impurities 
•  Procedure
Solution A, Mobile phase, Diluent, System suitability 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 methanol
Standard solution:  4 µg/mL of USP Diclofenac Related Compound A RS from the Standard stock solution in Diluent
Analysis:  Measure the peak responses over a period of 40 min.
Calculate the percentage of diclofenac related compound A in relation to the quantity of diclofenac sodium in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of diclofenac related compound A from the Sample solution
rS== peak response of diclofenac related compound A from the Standard solution
CS== concentration of USP Diclofenac Related Compound A RS in the Standard solution (mg/mL)
CU== nominal concentration of diclofenac sodium in the Sample solution (mg/mL)
Calculate the percentage of each impurity other than diethyl phthalate, if present, in relation to the diclofenac sodium in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response for each impurity from the Sample solution
rS== peak response for each impurity from the Standard solution
CS== concentration of USP Diclofenac Related Compound A RS in the Standard solution (mg/mL)
CU== nominal concentration of diclofenac sodium in the Sample solution (mg/mL)
Acceptance criteria 
Individual impurities:  NMT 0.5% of diclofenac related compound A; NMT 1.0% of any other individual impurity
Total impurities:  NMT 1.5%
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight, light-resistant containers.
•  USP Reference Standards 11
USP Diclofenac Sodium RS Click to View Structure
USP Diclofenac Related Compound A RS Click to View Structure
N-(2,6-Dichlorophenyl)indolin-2-one.
    C14H9Cl2NO        278.14
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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.
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(GCDF2010) General Chapters - Dosage Forms
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