Flecainide Tablets

Action and use

Class I antiarrhythmic.

Definition

Flecainide Tablets contain Flecainide Acetate.

Content of flecainide acetate, C₁₇H₂₀F₆N₂O₃,C₂H₄O₂

95.0 to 105.0% of the stated amount.

Identification

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900 mL of 0.1m hydrochloric acid and rotate the paddle at 100 revolutions per minute. Withdraw a sample of 5 mL of the medium, filter and dilute the filtered solution, if necessary, with sufficient 0.1m hydrochloric acid to produce a solution expected to contain about 0.005% w/v of flecainide acetate. Measure the absorbance of the solution at the maximum at 298 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell. Calculate the total content of flecainide acetate, C₁₇H₂₀F₆N₂O₃,C₂H₄O₂, in the medium from the absorbance of a 0.005% w/v solution of flecainide acetate BPCRS in 0.1m hydrochloric acid using the declared content of C₁₇H₂₀F₆N₂O₃,C₂H₄O₂ in flecainide acetate BPCRS.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using a TLC silica gel F₂₅₄ plate (Merck plates are suitable) and a mixture of 2 volumes of methanol, 5 volumes of 18m ammonia, 100 volumes of acetone and 100 volumes of dichloromethane as the mobile phase but allowing the solvent front to ascend 10 cm above the line of application. Apply separately to the plate 1 µL of each of the following solutions. For solution (1) add 2 mL of methanol to a quantity of the powdered tablets containing 0.2 g of flecainide acetate, shake, centrifuge and use the supernatant liquid. Solution (2) contains 0.05% w/v of flecainide acetate BPCRS in methanol. Solution (3) contains 0.05% w/v of flecainide impurity A EPCRS in methanol. Solution (4) contains 0.02% w/v of flecainide impurity B EPCRS in methanol. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). In the chromatogram obtained with solution (1) any spot corresponding to 3-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-1,5,6,7,8,8ahexahydroimidazo[1,5-a]pyridine (impurity A) is not more intense than the principal spot in the chromatogram obtained with solution (3) (0.5%). Spray the plate with a freshly prepared 0.2% w/v solution of ninhydrin in absolute ethanol, heat the plate at 105^o for approximately 5 minutes and examine immediately. In the chromatogram obtained with solution (1) any bluish-purple spot corresponding to (piperidin-2-yl)methanamine (impurity B) is not more intense than the principal spot in the chromatogram obtained with solution (4) (0.2%) and any other secondary spot is not more intense than the principal spot in the chromatogram obtained with solution (2) (0.5%).

Assay

Shake 20 tablets with 100 mL of a 2% v/v solution of lactic acid until the tablets have disintegrated, add 650 mL of water, shake with the aid of ultrasound for 30 minutes, add sufficient water to produce 1000 mL, mix and filter (Whatman GF/F paper is suitable), discarding the first 100 mL of filtrate. Dilute the filtrate with a 0.2% v/v solution of lactic acid to produce a solution containing 0.01% w/v of flecainide acetate and measure the absorbance of the resulting solution at the maximum at about 296 nm, Appendix II B, using a 0.2% v/v solution of lactic acid in the reference cell. Calculate the content of C₁₇H₂₀F₆N₂O₃,C₂H₄O₂ in the tablets from the absorbance obtained with a solution containing 0.01% w/v of flecainide acetate BPCRS in a 0.2% v/v solution of lactic acid and using the declared content of C₁₇H₂₀F₆N₂O₃,C₂H₄O₂ in flecainide acetate BPCRS.

Storage

Flecainide Tablets should be stored at a temperature not exceeding 30°.

IMPURITIES

The impurities limited by the requirements of this monograph include impurities A, B and D stated under Flecainide Acetate.