Accessed from 10.6.1.1 by apman3 on Fri Feb 05 11:27:55 EST 2016
`
`USP 38
`
`Official Monographs / Diclofenac 3087
`
`USP Monographs
`
`centage of the labeled amount of diclofenac potassium
`(C14H10Cl2KNO2) in the portion of the Tablets 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 obtained from the Assay preparation
`and the Standard preparation, respectively.
`
`.
`
`Diclofenac Sodium
`
`C14H10Cl2NNaO2 318.13
`Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, mono-
`sodium 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 percent of
`C14H10Cl2NNaO2, calculated on the dried basis.
`Packaging and storage—Preserve in tight, light-resistant
`containers.
`USP Reference standards Æ11æ—
`USP Diclofenac Sodium RS
`USP Diclofenac Related Compound A RS
`N-(2,6-Dichlorophenyl)indolin-2-one.
`C14H9Cl2NO 278.14
`Identification—
`A: Infrared Absorption Æ197Kæ.
`B: The retention time of the diclofenac peak in the chro-
`matogram of the Test solution corresponds to that of the
`Resolution solution as obtained in the test for Chromato-
`graphic purity.
`C: The residue obtained by igniting it responds to the
`flame test for Sodium Æ191æ.
`Color of solution—A 1 in 20 solution of it in methanol is
`colorless to faintly yellow, and the absorbance of the solu-
`tion, determined in a 1-cm cell at 440 nm, is not more than
`0.050, methanol being used as the blank.
`Clarity of solution—The 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 Æ791æ:
` between 7.0 and 8.5, in a solution (1 in 100).
`Loss on drying Æ731æ—Dry it at 105(cid:176) to 110(cid:176) for 3 hours:
`it loses not more than 0.5% of its weight.
`
`Delete the following:
`•.Heavy metals, Method II Æ231æ—To prepare the Test Prep-
`aration, use a 100-mL borosilicate glass beaker or a quartz
`crucible. If the residue is not completely white after the igni-
`tion at 500(cid:176) to 600(cid:176), add enough hydrogen peroxide to
`dissolve it, heat gently until dry, and ignite for 1 hour. Re-
`peat the hydrogen peroxide treatment and ignition until the
`residue is completely white. Proceed as directed in Test Prep-
`
`aration, beginning with “Cool, add 4 mL of 6 N hydrochlo-
`ric acid.” The limit is 0.001%.• (Official 1-Dec-2015)
`Chromatographic purity—
`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 appropri-
`ate 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 ad-
`justments if necessary (see System Suitability under Chroma-
`tography Æ621æ). [ NOTE—Increasing the proportion of buffer
`increases resolution.]
`Diluent—Prepare a mixture of methanol and water
`(70:30).
`Standard solution—Prepare a solution of USP Diclofenac
`Related Compound A RS in methanol having a known con-
`centration 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 mg per mL.
`Resolution solution—Prepare a solution in Diluent contain-
`ing 20 mg of diethyl phthalate, 7.5 mg of USP Diclofenac Re-
`lated Compound A RS, and 0.75 mg of USP Diclofenac So-
`dium RS per mL.
`Test solution—Transfer about 75 mg of Diclofenac So-
`dium, accurately weighed, to a 100-mL volumetric flask, dis-
`solve in and dilute with Diluent to volume, and mix.
`Chromatographic system (see Chromatography Æ621æ)—The
`liquid chromatograph is equipped with a 254-nm detector
`and a 4.6-mm · 25-cm column containing packing L7 (end-
`capped). The flow rate is about 1 mL per minute. Chromat-
`ograph the Resolution solution, and record the peak re-
`sponses 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 resolu-
`tion, 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%.
`Procedure—Separately inject equal volumes (about 10 mL)
`of the Standard solution and the Test solution into the chro-
`matograph, record the chromatograms, and measure the
`peak responses over a period of 2.5 times the retention time
`of diclofenac. Calculate the percentage 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 mg 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 percentage 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 impu-
`rity is found. The sum of all of the impurities found is not
`more than 0.5%.
`Assay—Dissolve about 450 mg of Diclofenac Sodium, accu-
`rately weighed, in 25 mL of glacial acetic acid, and titrate
`with 0.1 N perchloric acid VS, determining the endpoint
`potentiometrically. Perform a blank determination, and
`
`Official from December 1, 2015
`Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
`
`Page 1 of 2
`
`

`
`Accessed from 10.6.1.1 by apman3 on Fri Feb 05 11:27:55 EST 2016
`
`3088 Diclofenac / Official Monographs
`
`USP 38
`
`rS
`
`make any necessary correction. Each mL of 0.1 N perchloric
`acid is equivalent to 31.81 mg of C14H10Cl2NNaO2.
`
`.
`
`Diclofenac Sodium Delayed-Release
`Tablets
`
` It meets
`
`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 Sam-
`ple solution corresponds to that of the Standard solution,
`as obtained in the Assay.
`• B. IDENTIFICATION TESTS—GENERAL, Sodium Æ191æ:
`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 nec-
`essary, adjust with additional portions of the appropri-
`ate 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 mg/mL of diethyl
`phthalate, 7.5 mg/mL of USP Diclofenac Related Com-
`pound A RS, and 0.75 mg/mL of USP Diclofenac So-
`dium RS in Diluent
`Standard solution: 0.75 mg/mL of USP Diclofenac So-
`dium RS in Diluent
`Sample solution: Transfer 20 Tablets to a volumetric
`flask of such capacity that when filled to volume, a con-
`centration of 0.75 mg/mL of diclofenac sodium is ob-
`tained. 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-mm or finer pore size,
`and use the filtrate as the Sample solution.
`Chromatographic system
`(See Chromatography Æ621æ, System Suitability.)
`Mode: LC
`Detector: UV 254 nm
`Column: 4.6-mm · 25-cm; packing L7 (end-capped)
`Flow rate: 1 mL/min
`Injection size: 10 mL
`System suitability
`Samples: System suitability solution and Standard
`solution
`[NOTE—The relative retention times for diethyl phthal-
`ate, 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) · (C S/CU) · 100
`= peak response of diclofenac from the Sample
`solution
`
`rU
`
`USP Monographs
`
`CS
`
`CU
`
` Meet the
`
`= peak response of diclofenac from the Standard
`solution
`= concentration of USP Diclofenac Sodium RS in
`the Standard solution (mg/mL)
`= nominal concentration of diclofenac sodium in
`the Sample solution (mg/mL)
`Acceptance criteria: 90.0%–110.0%
`PERFORMANCE TESTS
`• DISSOLUTION Æ711æ:
` Proceed as directed for Procedure, Ap-
`paratus 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 mg/mL of USP Diclofenac Sodium RS.
`Sample solution: At the end of 2 h, remove each Tab-
`let, 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 so-
`dium 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 hydro-
`chloric 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 vol-
`ume, and mix. Transfer 3.0 mL of this solution to a
`100-mL volumetric flask, dilute with Buffer stage Me-
`dium to volume, and mix. The final concentration is
`about 0.0204 mg/mL of diclofenac sodium.
`Sample solution: Sample per Dissolution Æ711æ. 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 Æ905æ:
`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 mg/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.
`
`Official from December 1, 2015
`Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
`
`Page 2 of 2