Digoxin Tablets

Action and use

Na/K-ATPase inhibitor; cardiac glycoside.

Definition

Digoxin tablets contain digoxin.

Content of digoxin, C₄₁H₆₄O₁₄

90.0 to 110.0% of the stated amount.

Identification

To a quantity of the powdered tablets containing 0.25 mg of Digoxin, add 1 mL of glacial acetic acid containing 0.01% w/v of iron(iii) chloride hexahydrate, shake for a few minutes, filter through sintered glass and cautiously add 1 mL of sulfuric acid without mixing. A brown ring, free from red colour, is produced at the interface and, after a short time, an indigo colour is produced in the upper layer.

TESTS

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, placing six tablets in the basket, using as the medium 600 mL of water freshly prepared by distillation and rotating the basket at 120 revolutions per minute for 60 minutes. Withdraw a sample of 5 mL of the medium. Filter the sample through a membrane filter disc with a nominal pore size not greater than 0.8 µm, discarding the first 1 mL of the filtrate, and transfer 1 mL to a 10 mL graduated flask. Add 3 mL of a 0.1% w/v solution of l-ascorbic acid in methanol and 0.2 mL of a 0.009m solution of hydrogen peroxide, prepared by accurately diluting hydrogen peroxide solution (100 vol) that has been standardised by titration with 0.02m potassium permanganate VS, mix and dilute to volume with hydrochloric acid. After exactly 2 hours measure the fluorescence of the solution, Appendix II E, using an excitation wavelength of 360 nm and an emission wavelength of 490 nm and setting the instrument to zero with water and to 100 with a solution prepared at the same time as the test solution in the following manner. Dilute 2.5 mL of a 0.100% w/v solution of digoxin EPCRS in ethanol (80%) to 100 mL with water, dilute the resulting solution further with water to produce a solution containing in 1 mL an amount of Digoxin equal to one-hundredth of the strength of the tablets being examined, transfer 1 mL of the solution to a 10 mL graduated flask and carry out the operation described above, beginning at the words ‘Add 3 mL ... ‘. The amount of digoxin, C₄₁H₆₄O₁₄, per tablet in solution is not less than 75% of the stated amount.

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Digoxin comply with the requirements stated under Tablets using the following method of analysis. For tablets containing 0.125 mg of digoxin, place one tablet in 5 mL of water at 37°, agitate to disintegrate, add 28 mL of ethanol (96%), shake for 1 hour and add sufficient ethanol (80%) to produce 50 mL. For tablets containing more or less than 0.125 mg of Digoxin carry out the same procedure but using correspondingly greater or smaller quantities of water, ethanol (96%) and ethanol (80%). Filter the resulting solution through a suitable membrane filter disc with a nominal pore size not greater than 0.8 µm, discarding the first few mL of the filtrate, and transfer 1.0 mL to a 10 mL graduated flask. Add 3 mL of a 0.1% w/v solution of l-ascorbic acid in methanol, 0.2 mL of a 0.009m solution of hydrogen peroxide prepared by accurately diluting hydrogen peroxide solution (100 vol) that has been standardised by titration with 0.02m potassium permanganate VS, mix and dilute to volume with hydrochloric acid. After exactly 2 hours measure the fluorescence of the solution, Appendix II E, using an excitation wavelength of 360 nm and an emission wavelength of 490 nm and setting the instrument to zero with water. Calculate the content of digoxin, C₄₁H₆₄O₁₄, from the fluorescence obtained by carrying out the operation at the same time using a solution containing 2.5 µg per mL of digoxin EPCRS in ethanol (80%) and beginning at the words ‘transfer 1.0 mL ...’.

Assay

Weigh and finely powder 20 tablets. To a quantity of the powder containing 1.25 mg of Digoxin add 3 mL of water, swirl to disperse the powder and allow to stand for 10 minutes swirling occasionally. Add 25 mL of glacial acetic acid, shake for 1 hour and filter (Whatman No. 1 paper is suitable), discarding the first few mL. To 4 mL of the filtrate add 1 mL of dimethyl sulfoxide, dilute to 25 mL with xanthydrol reagent, mix well and allow to stand in the dark for 4 hours (solution A). At the same time prepare two further solutions in the same manner but using for solution B 4 mL of digoxin standard solution and for solution C 4 mL of a mixture of 25 volumes of glacial acetic acid and 3 volumes of water and beginning at the words ‘add 1 mL of dimethyl sulfoxide ...’. Measure the absorbances of solutions A and B at the maximum at 545 nm, Appendix II B, using solution C in the reference cell.