Identification
A:
The retention time of the diclofenac peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B:
It meets the requirements of the flame test for
Sodium 191.
Dissolution 711
Proceed as directed for
Procedure for
Method B under
Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms.
acid stage
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 2
(paddles constructed of, or coated with, polytef being used): 50 rpm.
Procedure
At the end of 2 hours, remove each Tablet, or the major portion thereof if the Tablet is not intact, from the individual vessels, and subject them to the test in the
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 minutes. Determine the amount of C
14H
10Cl
2NNaO
2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solution under test in comparison with a Standard solution prepared as follows. Transfer about 68 mg of
USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. 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 about 13.6 µg of
USP Diclofenac Sodium RS per mL.
buffer stage
pH 6.8 Phosphate buffer
Dissolve 76 g of tribasic sodium phosphate in water to obtain 1000 mL of solution. Mix 250 mL of this solution with 750 mL of 0.1 N hydrochloric acid, and, if necessary, adjust with 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.05.
Medium:
pH 6.8 Phosphate buffer; 900 mL.
Apparatus 2:
50 rpm.
Procedure
At the end of 45 minutes, determine the amount of C
14H
10Cl
2NNaO
2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solutions under test, suitably diluted with
Medium, in comparison with a Standard solution prepared as follows. Transfer about 68 mg of
USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 2.0 mL of this solution to a second 100-mL volumetric flask, dilute with
Medium, as obtained in the
Buffer stage, to volume, and mix. This Standard solution contains about 0.02 mg of
USP Diclofenac Sodium RS per mL.
Tolerances
Not less than 75% (Q) of the labeled amount of C14H10Cl2NNaO2 is dissolved.
Chromatographic purity
pH 2.5 Phosphate buffer, Mobile phase, Diluent, Resolution solution, and Chromatographic system
Proceed as directed in the Assay.
Standard solution
Prepare a solution having a known concentration of about 0.8 mg per mL of
USP Diclofenac Related Compound A RS in methanol. Dilute an accurately measured volume of this stock solution with
Diluent to obtain a solution having a known concentration of about 4 µg per mL.
Test solution
Use the Assay preparation, prepared as directed in the Assay.
Procedure
Separately inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the peak responses over a period of 40 minutes. Calculate the percentage of diclofenac related compound A in relation to the quantity of diclofenac sodium in the Tablets taken by the formula:
10(C/A)(rU / rS)
in which
C is the concentration, in µg per mL, of
USP Diclofenac Related Compound A RS in the
Standard solution; A is the quantity, in mg, of diclofenac sodium (C
14H
10Cl
2NNaO
2) in the Tablets taken for the
Assay, as determined in the
Assay; and
rU and
rS are the diclofenac related compound A peak responses obtained from the
Test solution and the
Standard solution, respectively: not more than 0.5% is found. Calculate the percentage of each other impurity, other than diethyl phthalate, if present, in relation to the diclofenac sodium in the Tablets taken by the formula:
10(C/A)(ri / rS)
in which
ri is the peak response for each impurity obtained from the
Test solution, and the other terms are as defined above: not more than 1.0% of any individual impurity is found, and not more than 1.5% of total impurities is found.
Assay
pH 2.5 Phosphate buffer
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
Prepare a filtered and degassed mixture of methanol and
pH 2.5 Phosphate buffer (700:300). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
[noteIncreasing the proportion of buffer increases resolution.
]
Diluent
Prepare a mixture of methanol and water (70:30).
Standard preparation
Prepare a solution of
USP Diclofenac Sodium RS in
Diluent having a known concentration of about 0.75 mg per mL.
Assay preparation
Transfer 20 Tablets to a volumetric flask of such capacity that when filled to volume, a concentration of about 0.75 mg of diclofenac sodium per mL is obtained. Add Diluent to about 70% of the capacity of the flask, and shake by mechanical means for not less than 30 minutes to disintegrate the Tablets. Cool to room temperature, dilute with Diluent to volume, and mix. Pass a portion of the solution through a filter having a 0.5-µm or finer porosity, and use the filtrate as the Assay preparation.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L7 (end-capped). The flow rate is about 1 mL per minute. Chromatograph the
Resolution solution, and record the peak responses as directed for
Procedure: the relative retention times are about 0.5 for diethyl phthalate, 0.6 for diclofenac related compound A, and 1.0 for diclofenac; and the resolution,
R, between diethyl phthalate and diclofenac related compound A is not less than 2.2, and between diclofenac related compound A and diclofenac is not less than 6.5. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 10 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of diclofenac sodium (C
14H
10Cl
2NNaO
2) in each Tablet taken by the formula:
(VC / 20)(rU / rS)
in which
C is the concentration, in mg per mL, of
USP Diclofenac Sodium RS in the
Standard preparation; V is the volume of the flask used, in mL; and
rU and
rS are the diclofenac peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.