Clemastine Tablets

General Notices

Action and use

Histamine H1 receptor antagonist; antihistamine.

Definition

Clemastine Tablets contain Clemastine Fumarate.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of clemastine, C21H26ClNO

93.0 to 105.0% of the stated amount.

Identification

A. In the test for Related substances, the principal spot in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (3).
B. In the test for 1-(4-Chlorophenyl)-1-phenylethanol, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the peak in the chromatogram obtained with solution (3).

Tests

1-(4-Chlorophenyl)-1-phenylethanol

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add to a quantity of the powdered tablets, containing the equivalent of 10 mg of clemastine, 200 mL of a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate, shake vigorously for 45 minutes, centrifuge at a speed of at least 4000 revolutions per minute for 10 minutes and use the supernatant liquid.
(2) 0.0000335% w/v of 1-(4-chlorophenyl)-1-phenylethanol BPCRS in a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.
(3) 0.0067% w/v of clemastine fumarate BPCRS in a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.
(4) 0.000335% w/v of clemastine fumarate BPCRS and 0.000064% w/v of 1-(4-chlorophenyl)-1-phenylethanol BPCRS in a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.
chromatographic conditions

The chromatographic conditions described under Assay may be used. Inject 100 µL of each solution.

system suitability

The test is not valid unless the resolution between the peaks due to clemastine fumarate and 1-(4-chlorophenyl)-1-phenylethanol in the chromatogram obtained with solution (4) is at least 2.2.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 1-(4-chlorophenyl)-1-phenylethanol is not greater than the area of the peak in the chromatogram obtained with solution (2) (0.5%, calculated with reference to clemastine fumarate).

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Shake a quantity of the powdered tablets containing the equivalent of 8 mg of clemastine with 4 mL of methanol for 15 minutes, centrifuge at 4000 revolutions per minute for 10 minutes and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 10 volumes with methanol.
(3) 0.027% w/v of clemastine fumarate BPCRS in methanol.
(4) 0.00135% w/v of clemastine fumarate BPCRS in methanol.
(5) 0.0135% w/v of each of clemastine fumarate BPCRS and diphenhydramine hydrochloride BPCRS in methanol.
(6) 0.00135% w/v of 2-(2-hydroxyethyl)-1-methylpyrrolidine BPCRS in methanol.
chromatographic conditions
(a) Use as the coating silica gel 60 F254 (Merck plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 20 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in a current of cold air for 5 minutes, spray with a freshly prepared mixture of 1 volume of potassium iodobismuthate solution and 10 volumes of 2m acetic acid and then with hydrogen peroxide solution (10 vol). Cover the plate immediately with a glass plate of the same size and examine the chromatograms after 2 minutes.
mobile phase

1 volume of 13.5m ammonia, 20 volumes of methanol and 80 volumes of stabiliser-free tetrahydrofuran.

system suitability

The test is not valid unless the chromatogram obtained with solution (5) shows two clearly separated spots.

limits

In the chromatogram obtained with solution (1):

any spot corresponding to 2-(2-hydroxyethyl)-1-methylpyrrolidine is not more intense than the spot in the chromatogram obtained with solution (6) (0.5%, with reference to clemastine fumarate);

any orange-brown secondary spot is not more intense than the spot in the chromatogram obtained with solution (4) (0.5%, with reference to clemastine fumarate).

Disregard any spot remaining on the line of application and any spot with an Rf value greater than that of the principal spot.

Uniformity of content

Tablets containing the equivalent of less than 2 mg and/or less than 2% w/w of clemastine comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Vigorously shake one tablet with 40 mL of a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate for 45 minutes and centrifuge until a clear supernatant liquid is obtained.
(2) 0.00335% w/v of clemastine fumarate BPCRS in a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 10 µL of each solution.
mobile phase

0.1 volume of orthophosphoric acid, 50 volumes of acetonitrile and 50 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.

determination of content

Calculate the content of C21H26ClNO in each tablet using the declared content of C21H26ClNO in clemastine fumarate BPCRS.

Assay

For tablets containing the equivalent of less than 2 mg and/or less than 2% w/w of clemastine

Use the average of the individual results determined in the test for Uniformity of content.

For tablets containing the equivalent of 2 mg or more and 2% w/w or more of clemastine

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add to a quantity of the powdered tablets containing the equivalent of 10 mg of clemastine 200 mL of a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate, shake vigorously for 45 minutes, centrifuge at a speed of at least 4000 revolutions per minute for 10 minutes and use the supernatant liquid.
(2) 0.0067% w/v of clemastine fumarate BPCRS in a mixture of 25 volumes of acetonitrile and 75 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable),
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 10 µL of each solution.
mobile phase

0.1 volume of orthophosphoric acid, 45 volumes of acetonitrile and 55 volumes of a 1% w/v solution of ammonium dihydrogen orthophosphate.

determination of content

Calculate the content of C21H26ClNO in the tablets using the declared content of C21H26ClNO in clemastine fumarate BPCRS.

Labelling

The quantity of the active ingredient is stated in terms of the equivalent amount of clemastine.