Warfarin Tablets
Warfarin Tablets prepared from Warfarin Sodium are not necessarily interchangeable with Warfarin Tablets prepared from Warfarin Sodium Clathrate.
Action and use
Vitamin K epoxide reductase inhibitor; oral anticoagulant (coumarin).
Definition
Warfarin Tablets contain Warfarin Sodium or Warfarin Sodium Clathrate.
Content of warfarin sodium, C19H15NaO4
95.0 to 105.0% of the stated amount.
Identification
Extract a quantity of the powdered tablets containing the equivalent of 0.1 g of warfarin sodium with 30 mL of water, add 0.1 mL of 2m hydrochloric acid, filter, wash the precipitate with water and dry. Warm the residue gently with 3 mL of ethanol (96%), filter and add the filtrate to 25 mL of water containing 0.1 mL of 2m hydrochloric acid. Filter, wash the precipitate with water and dry it at 105°. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of warfarin (RS 361).
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
After 45 minutes, withdraw a 10-mL sample of the medium. Measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maxima at 307 nm and 360 nm, Appendix II B, using the dissolution medium in the reference cell.
Calculate the difference between the two readings (ΔA). Calculate the total content of warfarin sodium, C19H15NaO4, in the medium from the absorbances obtained and taking 428 as the value of ΔA(1%, 1 cm).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mixture of methanol (25%).
1 volume of glacial acetic acid, 15 volumes of acetonitrile and 85 volumes of water.
When the chromatograms are recorded under the prescribed conditions, the retention times relative to warfarin (retention time about 9 minutes) are: impurity B, about 0.4 and impurity C, about 0.6.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity B and impurity C is at least 2.0.
Identify any peaks corresponding to impurity B and impurity C in the chromatogram obtained with solution (1), using the chromatogram obtained with solution (3). Multiply the area of any peak corresponding to impurity B by a correction factor of 0.5 and impurity C by a correction factor of 0.4.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity B and impurity C is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.15% of each);
the area of any other secondary peak is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any other secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of warfarin sodium 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 volume of glacial acetic acid, 45 volumes of water, and 55 volumes of acetonitrile.
Calculate the content of C19H15NaO4 in each tablet using the declared content of C19H16O4 in warfarin BPCRS. Each mg of C19H16O4 is equivalent to 1.071 mg of C19H15NaO4.
Assay
For tablets containing 2 mg or less or 2% w/w or less of warfarin sodium
Use the average of the individual results obtained in the test for Uniformity of content.
For tablets containing more than 2 mg and more than 2% w/w of warfarin sodium
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Uniformity of content may be used.
Calculate the content of C19H15NaO4 in the tablets using the declared content of C19H16O4 in warfarin BPCRS. Each mg of C19H16O4 is equivalent to 1.071 mg of C19H15NaO4.
Storage
Warfarin Tablets should be protected from light.
Labelling
When the active ingredient is Warfarin Sodium Clathrate the quantity is stated in terms of the equivalent amount of warfarin sodium.
Impurities
The impurities limited by the requirements of this monograph include those listed under Warfarin Sodium.