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 TestsGeneral, 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)
[NoteIncreasing 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
[NoteThe 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
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
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
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.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2881
Pharmacopeial Forum: Volume No. 35(5) Page 1129
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