Accessed from 122.180.123.

34 by anware10 on Fri Dec 23 01:50:11 EST 2011

2880 Diclofenac / Official Monographs

AssayDissolve about 300 mg of Diclofenac Potassium, accurately weighed, in 50 mL of glacial acetic acid, and titrate with 0.1 N per chloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 N per chloric acid is equivalent to 33.424 mg of C 14H10Cl2KNO2.

USP 35
sponses. Calculate the per centage of diclofenac related compound A relative to the diclofenac potassium labeled content in the portion of T ablets taken by the formula: 100 0.001(CA / CT)(rU / rS) in which 0.001 is a conversion coefficient from g per mL to mg per mL; CA is the concentration, in g per mL, of diclofenac related compound A in the Standard solution; CT is the concentration, in mg per mL, of diclofenac potassium in the Test solution, based on the label claim; 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% of diclofenac related compound A is found. Calculate the percentage of each of the other impurities, other than diethyl phthalate, if present, relative to the diclofenac potassium labeled content in the portion of T ablets taken by the formula: 100 0.001(CA / CT)(ri / rS) in which ri is the response of an individual impurity peak obtained from the Test solution, and the other terms are as defined above: not more than 0.5% of each individual impurity is found, and not more than 1.5% of total impurities is found. Assay pH 2.5 Phosphate bufferMix equal volumes of 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. If necessary, adjust with additional portions of the appropriate components to a pH of 2.5 0.2. Mobile phasePrepare a filtered and degassed mixture of methanol and pH 2.5 Phosphate buffer (70:30). Make adjustments if necessar y (see System Suitability under Chromatography 621). DiluentPrepare a mixture of methanol and water (70:30). Standard preparationDissolve an accurately weighed quantity of USP Diclofenac Potassium RS in Diluent, and dilute quantitatively, and stepwise if necessar y, to obtain a solution having a known concentration of about 0.5 mg per mL. Assay preparationWeigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 50 mg of diclofenac potassium, to a 100-mL volumetric flask. Add about 70 mL of Diluent, stir for 60 minutes, dilute with Diluent to volume, mix, and centrifuge. Resolution solutionPrepare a solution in Diluent containing 40 g per mL of diethyl phthalate, 0.5 mg per mL of USP Diclofenac Potassium RS, and 37.5 g per mL of USP Diclofenac Potassium Related Compound A RS. 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 5- m packing L7. The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between diethyl phthalate and diclofenac related compound A is not less than 2.5, and the resolution, R, between diclofenac related compound A and diclofenac is not less than 3.5. 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%. ProcedureSeparately inject equal volumes (about 10 L) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the per centage of the labeled amount of diclofenac potassium (C 14H10Cl2KNO2) in the portion of the T ablets taken by the formula: 100(CS / CU)(rU / rS) in which CS is the concentration, in mg per mL, of diclofenac potassium in the Standard preparation; CU is the concentration, in mg per mL, of diclofenac potassium in the Assay preparation, based on the label claim; and rU and rS are the peak responses

Diclofenac Potassium Tablets

.

Diclofenac Potassium T ablets contain not less than 90.0 per cent and not more than 110.0 percent of the labeled amount of diclofenac potassium (C 14H10Cl2KNO2).
Packaging and storagePreserve in tight, light-resistant containers, and store at controlled room temperature. USP Reference standards 11 USP Diclofenac Potassium RS USP Diclofenac Related Compound A RS N-(2,6-Dichlorophenyl)indolin-2-one. C14H9Cl2NO 278.14 Identification A: The retention time of the diclofenac peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay. B: It meets the requirements of the flame test for Potassium 191. Dissolution 711 Medium: simulated intestinal fluid (without enzyme); 900 mL. Apparatus 2: 50 rpm. Time: 60 minutes. ProcedureDetermine the amount of C 14H10Cl2KNO2 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 276 nm on portions of the solution under test passed through a 0.45- m filter, suitably diluted with Medium, if necessar y, in comparison with a Standard solution having a known concentration of USP Diclofenac Potassium RS in the same Medium. Calculate the per centage of diclofenac potassium (C 14H10Cl2KNO2) dissolved by the formula:

in which AU and AS are the absorbances obtained from the solution under test and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the T ablet label claim, in mg, of diclofenac potassium. TolerancesNot less than 75% ( Q) of the labeled amount of C14H10Cl2KNO2 is dissolved in 60 minutes. Uniformity of dosage units: meets the requirements. Related compounds pH 2.5 Phosphate buffer, Mobile phase, Diluent, Resolution solution, and Chromatographic systemPrepare as directed in the Assay. Standard solutionDissolve an accurately weighed quantity of USP Diclofenac Related Compound A RS in Diluent, and dilute quantitatively, and stepwise if necessar y, to obtain a solution having a known concentration of about 2.5 g per mL. Test solutionUse the Assay preparation. ProcedureSeparately inject equal volumes (about 30 L) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak re-

Official from May 1, 2012 Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved.

Accessed from 122.180.123.34 by anware10 on Fri Dec 23 01:50:11 EST 2011

USP 35
obtained from the Assay preparation and the Standard preparation, respectively.

Official Monographs / Diclofenac 2881

tion of about 0.75 mg per mL. Quantitatively dilute an accurately measured volume of this stock solution with Diluent to obtain a solution having a known concentration of about 1.5 g per mL. Resolution solutionPrepare a solution in Diluent containing 20 g of diethyl phthalate, 7.5 g of USP Diclofenac Related Compound A RS , and 0.75 mg of USP Diclofenac Sodium RS per mL. Test solutionTransfer about 75 mg of Diclofenac Sodium, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix. Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm 25-cm column containing packing L7 (endcapped). 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 that between diclofenac related compound A and diclofenac is not less than 6.5. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5%. ProcedureSeparately inject equal volumes (about 10 L) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses over a period of 2.5 times the retention time of diclofenac. Calculate the per centage of diclofenac related compound A in the portion of Diclofenac Sodium taken by the formula: 10(C / W)(rU / rS) in which C is the concentration, in g per mL, of USP Diclofenac Related Compound A RS in the Standard solution; W is the quantity, in mg, of Diclofenac Sodium taken to prepare the Test solution; 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 0.2% is found. Calculate the per centage of each other impurity in the portion of Diclofenac Sodium taken by the formula: 10(C / W)(ri / rS) in which ri is the response of an individual impurity peak obtained from the Test solution, and the other terms are as defined above: not more than 0.2% of any individual impurity is found. The sum of all of the impurities found is not more than 0.5%. AssayDissolve about 450 mg of Diclofenac Sodium, accurately weighed, in 25 mL of glacial acetic acid, and titrate with 0.1 N per chloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N per chloric acid is equivalent to 31.81 mg of C 14H10Cl2NNaO2.

Diclofenac Sodium
.

C14H10Cl2NNaO2 318.13 Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, monosodium salt. Sodium [o-(2,6-dichloroanilino)phenyl]acetate [15307-79-6].

Diclofenac Sodium contains not less than 99.0 percent and not more than 101.0 per cent of C14H10Cl2NNaO2, calculated on the dried basis.
Packaging and storagePreserve in tight, light-resistant containers. USP Reference standards 11 USP Diclofenac Sodium RS USP Diclofenac Related Compound A RS N-(2,6-Dichlorophenyl)indolin-2-one. C14H9Cl2NO 278.14 Identification A: Infrared Absorption 197K. B: The retention time of the diclofenac peak in the chromatogram of the Test solution corresponds to that of the Resolution solution as obtained in the test for Chromatographic purity. C: The residue obtained by igniting it responds to the flame test for Sodium 191. Color of solutionA 1 in 20 solution of it in methanol is colorless to faintly yellow, and the absorbance of the solution, determined in a 1-cm cell at 440 nm, is not more than 0.050, methanol being used as the blank. Clarity of solutionThe solution prepared as directed under Color of solution is not significantly less clear than an equal volume of methanol contained in a similar vessel and examined similarly. pH 791: between 7.0 and 8.5, in a solution (1 in 100). Loss on drying 731Dry it at 105 to 110 for 3 hours: it loses not more than 0.5% of its weight. Heavy metals, Method II 231To prepare the Test Preparation, use a 100-mL borosilicate glass beaker or a quartz crucible. If the residue is not completely white after the ignition at 500 to 600, add enough hydrogen peroxide to dissolve it, heat gently until dr y, and ignite for 1 hour. Repeat the hydrogen peroxide treatment and ignition until the residue is completely white. Proceed as directed in Test Preparation, beginning with Cool, add 4 mL of 6 N hydrochloric acid. The limit is 0.001%. Chromatographic purity pH 2.5 Phosphate bufferMix 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 phasePrepare a filtered and degassed mixture of methanol and pH 2.5 Phosphate buffer (700:300). Make adjustments if necessar y (see System Suitability under Chromatography 621). [ NOTEIncreasing the proportion of buffer increases resolution.] DiluentPrepare a mixture of methanol and water (70:30). Standard solutionPrepare a solution of USP Diclofenac Related Compound A RS in methanol having a known concentra-

Diclofenac Sodium Delayed-Release Tablets

.

DEFINITION Diclofenac Sodium Delayed-Release T ablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diclofenac sodium (C 14H10Cl2NNaO2). 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.

Official from May 1, 2012 Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved.