Tranexamic Acid Tablets

General Notices

Action and use

Antifibrinolytic.

Definition

Tranexamic Acid Tablets contain Tranexamic Acid.

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

Content of tranexamic acid, C8H15NO2

95.0 to 105.0% of the stated amount.

Identification

Shake a quantity of the powdered tablets containing 0.5 g of Tranexamic Acid with 5 mL of water for 15 minutes, filter and add 2 mL of ether to the filtrate. Stir, add 10 mL of methanol, stir again and allow to crystallise. The crystals, after drying, comply with the following tests.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of tranexamic acid (RS 344).
B. To 1 mL of a 1% w/v solution add 1 mL of a 0.2% w/v solution of ninhydrin in ethanol (96%) and heat on a water bath for 2 minutes. A dark bluish violet colour is produced.
C. Dissolve 0.2 g in 10 mL of 5m sodium hydroxide, add 0.2 mL of benzoyl chloride and shake vigorously for 10 minutes. Acidify to pH 4 with 2m hydrochloric acid, filter, wash the residue with 5 mL of ether and dry at 50° at a pressure of 2 kPa. The melting point of the residue is about 186°, Appendix V A.

Tests

Related substances

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

(1) Shake a quantity of the powdered tablets containing 1 g of Tranexamic Acid with 100 mL of water for 10 minutes, filter and use the filtrate.
(2) 0.01% w/v of tranexamic acid EPCRS in water.
(3) 0.001% w/v of 4-aminomethylbenzoic acid in water.
(4) 1% w/v of tranexamic acid impurity standard BPCRS in water.
chromatographic conditions
(a) Use a Stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.9 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 µL of each solution.

Inject solution (1) and allow the chromatography to proceed for 3 times the retention time of tranexamic acid (about 13 minutes). Identify the impurities from the chromatogram obtained with solution (4) and from the reference chromatogram supplied with tranexamic acid impurity standard BPCRS.

mobile phase

Dissolve 11.0 g of anhydrous sodium dihydrogen orthophosphate in 500 mL of water, add 5 mL of triethylamine and 1.4 g of sodium dodecyl sulfate, adjust the pH to 2.5 with 2m orthophosphoric acid and add sufficient water to produce 600 mL. Add 400 mL of methanol and mix.

system suitability

The test is not valid unless:

the chromatogram obtained with solution (4) closely resembles the reference chromatogram supplied with tranexamic acid impurity standard BPCRS;

the resolution factor between the peaks corresponding to tranexamic acid and impurity C in the chromatogram obtained with solution (4) is at least 2.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);

the area of any peak corresponding to impurity B is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any peak corresponding to impurity C is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%);

the area of any peak corresponding to impurity D is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%);

the area of any other secondary peak is not greater than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Assay

Weigh and powder 20 tablets. Dissolve a quantity of the powdered tablets containing 0.25 g of Tranexamic Acid in 50 mL of anhydrous acetic acid and carry out Method I for non-aqueous titration, Appendix VIII A, using crystal violet solution as indicator. Each mL of 0.1m perchloric acid VS is equivalent to 15.72 mg of C8H15NO2.

Impurities

A. trans,trans-4,4′-(iminodimethylene)di(cyclohexanecarboxylic) acid,
B. cis-4-(aminomethyl)cyclohexanecarboxylic acid,
C. (RS)-4-(aminomethyl)cyclohex-1-enecarboxylic acid,
D. 4-aminomethylbenzoic acid.