Disopyramide Phosphate Capsules

General Notices

Action and use

Class I antiarrhythmic.

Definition

Disopyramide Phosphate Capsules contain Disopyramide Phosphate.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of disopyramide, C21H29N3O

92.5 to 107.5% of the stated amount.

Identification

A. Suspend a quantity of the contents of the capsules containing the equivalent of 0.2 g of disopyramide in 50 mL of chloroform, add 2 mL of 13.5m ammonia, shake and filter through anhydrous sodium sulfate. Evaporate the filtrate to dryness using a rotary evaporator and dissolve the residue in 2 mL of chloroform. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of disopyramide (RS 110).
B. The light absorption, Appendix II B, in the range 230 to 350 nm of the solution obtained in the Assay exhibits a maximum only at 269 nm and a shoulder at 263 nm.
C. Shake a quantity of the contents of the capsules containing the equivalent of 0.4 g of disopyramide with 20 mL of water and filter. The filtrate yields the reactions characteristic of phosphates, Appendix VI.

TESTS

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of water at a temperature of 37°, as the medium.
procedure

After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 262 nm, Appendix II B, using water in the reference cell.

determination of content

Calculate the total content of disopyramide, C21H29N3O, in the medium taking 125 as the value of A(1%, 1 cm) at the maximum at 262 nm.

Related substances

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

(1) Shake a quantity of the contents of the capsules containing the equivalent of 0.20 g of disopyramide with 20 mL of methanol for 30 minutes and filter.
(2) Dilute 1 volume of solution (1) to 200 volumes with methanol.
chromatographic conditions
(a) Use as the coating silica gel F254.
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in a current of air and examine under ultraviolet light (254 nm).
mobile phase

1 volume of 18m ammonia, 30 volumes of acetone and 30 volumes of cyclohexane.

limits

Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).

Assay

To a quantity of the mixed contents of 20 capsules containing the equivalent of 40 mg of disopyramide, add 40 mL of 0.05m methanolic sulfuric acid, shake for 15 minutes, dilute to 100 mL with the same solvent and filter. Dilute 5 mL of the filtrate to 100 mL with 0.05m methanolic sulfuric acid and measure the absorbance of the resulting solution at the maximum at 269 nm, Appendix II B. Calculate the content of C21H29N3O taking 125 as the value of A(1%, 1 cm) at the maximum at 269 nm.

Labelling

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