Clemastine Fumarate Tablets
» Clemastine Fumarate Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C21H26ClNO·C4H4O4.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
Spray reagent Prepare as directed in the test for Chromatographic purity under Clemastine Fumarate.
Standard preparation Prepare a solution in a mixture of chloroform and methanol (1:1) having a concentration of about 2.5 mg of USP Clemastine Fumarate RS per mL.
Test preparation Place a portion of powdered Tablets, equivalent to about 2.5 mg of clemastine fumarate, in a glass-stoppered flask. Add 10 mL of a mixture of chloroform and methanol (1:1), and shake for 20 minutes. Filter, wash the residue with two 5-mL portions of the mixture of chloroform and methanol (1:1), and evaporate the combined filtrate and washings to dryness under vacuum. Dissolve the residue so obtained in 1 mL of the mixture of chloroform and methanol (1:1), and mix.
Procedure Proceed as directed for Procedure in the test for Chromatographic purity under Clemastine Fumarate, applying 5-µL portions of the Standard preparation and the Test preparation on the thin-layer chromatographic plate: the RF value of the principal spot obtained from the Test preparation corresponds to that obtained from the Standard preparation.
pH 4.0 citrate buffer Dissolve 20.0 g of monohydrate citric acid in about 1000 mL of water, add 22.0 mL of sodium hydroxide solution (3 in 10) and 8.8 mL of hydrochloric acid, and dilute with water to 2000 mL. Adjust, if necessary, with sodium hydroxide solution (1 in 2) to a pH of 4.0.
Medium: pH 4.0 citrate buffer; 500 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure Centrifuge 60 mL of the solution under test for 20 minutes at 4000 rpm, and transfer 50.0 mL of the supernatant to a 125-mL separator. To a second 125-mL separator transfer 50.0 mL of a Standard preparation that is prepared by dissolving an accurately weighed quantity of USP Clemastine Fumarate RS in Dissolution Medium and diluting quantitatively and stepwise with Dissolution Medium to yield a solution having a known concentration comparable with that of the solution under test. To a third 125-mL separator transfer 50.0 mL of Dissolution Medium to provide a blank. Treat each of the solutions in the three separators as follows. Add 10 mL of methyl orange solution (2 in 10,000), mix, add 20.0 mL of chloroform, shake simultaneously by mechanical means for 10 minutes, remove the chloroform layer, and centrifuge the chloroform layer for 10 minutes at 4000 rpm. Determine the amount of C21H26ClNO·C4H4O4 dissolved from absorbances at the wavelength of maximum absorbance at about 420 nm of the chloroform solutions obtained from the solution under test and the Standard preparation, using the chloroform solution obtained from the blank to set the instrument.
Tolerances Not less than 75% (Q) of the labeled amount of C21H26ClNO·C4H4O4 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
procedure for content uniformity
Dye solution Dissolve 100 mg of bromocresol purple in 1000 mL of 0.33 N acetic acid, and mix.
Acetous methanol Dilute 100 mL of methanol with sufficient 0.33 N acetic acid to prepare 1000 mL of solution, and mix.
Standard preparation Transfer about 27 mg of USP Clemastine Fumarate RS, accurately weighed, to a 100-mL volumetric flask, dissolve in 10 mL of methanol, dilute with 0.33 N acetic acid to volume, and mix. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, dilute with Acetous methanol to volume, and mix.
Test preparation Mix 1 finely powdered Tablet with an accurately measured volume of Acetous methanol, sufficient to obtain a solution having a concentration of about 27 µg of clemastine fumarate per mL. Shake for 30 minutes, and filter, discarding the first few mL of the filtrate.
Procedure Transfer 15.0 mL each of the Standard preparation, the Test preparation, and Acetous methanol to provide the blank to individual 125-mL separators. Add 25 mL of Dye solution and 50.0 mL of chloroform to each, and shake by mechanical means for 15 minutes. Allow the layers to separate, and filter the chloroform layers. Concomitantly determine the absorbances of the filtered solutions obtained from the Test preparation and the Standard preparation at the wavelength of maximum absorbance at about 406 nm, using the blank to set the instrument. Calculate the quantity, in mg, of C21H26ClNO·C4H4O4 in the Tablet taken by the formula:
(TC / D)(AU / AS)in which T is the labeled quantity, in mg, of clemastine fumarate in the Tablet; C is the concentration, in µg per mL, of USP Clemastine Fumarate RS in the Standard preparation; D is the concentration, in µg per mL, of clemastine fumarate in the Test preparation, based on the labeled quantity per Tablet and the extent of dilution; and AU and AS are the absorbances of the solutions from the Test preparation and the Standard preparation, respectively.
pH 7 phosphate buffer Transfer 9.47 g of anhydrous dibasic sodium phosphate to a 1000-mL volumetric flask, dilute with water to volume, and mix (flask A). Transfer 9.08 g of monobasic potassium phosphate to a 1000-mL volumetric flask, dilute with water to volume, and mix (flask B). Mix 612 mL of A with 388 mL of B.
Dilute phosphate buffer Prepare a mixture of 1 volume of pH 7 phosphate buffer and 3 volumes of water.
Mobile phase Prepare a suitable and degassed solution of methanol and Dilute phosphate buffer (83:17).
Standard preparation Dissolve an accurately weighed quantity of USP Clemastine Fumarate RS in a mixture of methanol and water (1:1) to obtain a solution having a known concentration of about 0.14 mg per mL.
Assay preparation Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 14 mg of clemastine fumarate, to a 200-mL conical flask. Pipet 100 mL of a mixture of methanol and water (1:1) into the flask, shake for 30 minutes, centrifuge, and filter the supernatant.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 4 mL per minute. Chromatograph five replicate injections of the Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation is not more than 1.5%.
Procedure Separately inject equal volumes (about 100 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C21H26ClNO·C4H4O4 in the portion of Tablets taken by the formula:
100C(rU / rS)in which C is the concentration, in mg per mL, of USP Clemastine Fumarate RS in the Standard preparation; and rU and rS are the peak responses of clemastine fumarate obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2699