Isradipine Tablets

General Notices

Action and use

Calcium channel blocker.

Definition

Isradipine Tablets contain Isradipine.

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

Content of isradipine, C19H21N3O5

95.0 to 105.0% of the stated amount.

Identification

A. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
B. Shake a quantity of the powdered tablets containing 3 mg of Isradipine with 70 mL of methanol (80%) for 10 minutes, dilute to 100 mL with the same solvent and filter. The light absorption of the filtrate, Appendix II B, in the range 250 to 450 nm exhibits a maximum at 326 nm.

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 500 mL of a 0.1% w/v solution of N,N-dimethyldodecylamine N-oxide and rotate the paddle at 50 revolutions per minute. Withdraw a sample of 10 mL of the medium and filter. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dilute 5 volumes of a 0.01% w/v solution of isradipine BPCRS in methanol (80%) to 100 volumes with a 0.1% w/v solution of N,N-dimethyldodecylamine N-oxide. Use the filtered dissolution medium as solution (2).

The chromatographic procedure may be carried out using (a) a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography R (5 µm) (Brownlee Spheri ODS 5µ is suitable), (b) methanol (80%) as the mobile phase with a flow rate of 2 mL per minute and (c) a detection wavelength of 326 nm. Inject 50 µL of each solution.

Calculate the content of C19H21N3O5 in the medium using the declared content of C19H21N3O5 in isradipine BPCRS.

Related substances

Carry out the test protected from light. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 50 mL of methanol (80%) to a number of whole tablets containing 50 mg of Isradipine, shake for 1 hour, centrifuge the resulting mixture and use the supernatant liquid. For solution (2) dilute 1 volume of solution (1) to 400 volumes with methanol (80%). Solution (3) contains 0.0009% w/v of isradipine impurity B BPCRS in the mobile phase. Solution (4) contains 0.0005% w/v of isradipine impurity D in the mobile phase. Solution (5) contains 0.010% w/v each of isradipine impurity D BPCRS and isradipine BPCRS in methanol (80%). For solution (1) allow the chromatography to proceed for 5 times the retention time of the principal peak.

The chromatographic procedure may be carried out using (a) a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Brownlee Spheri ODS 5µ is suitable), (b) as the mobile phase a mixture of 125 volumes of acetonitrile, 270 volumes of tetrahydrofuran and 625 volumes of water with a flow rate of 1.2 mL per minute and (c) a detection wavelength of 230 nm.

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution factor between the two principal peaks is at least 1.5.

In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (2) (0.25%), the area of any peak corresponding to isradipine impurity B is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.9%), and the area of any peak corresponding to isradipine impurity D is not greater than the area of the corresponding peak in the chromatogram obtained with solution (4) (0.5%). Calculate the percentage content of isradipine impurity B and isradipine impurity D using the respective reference solutions and the content of any unnamed impurities using solution (2). The total nominal content of impurities is not greater than 2%.

Assay

Carry out the assay protected from light. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 50 mL of methanol (80%) to a number of whole tablets containing 50 mg of Isradipine, shake for 1 hour, centrifuge the resulting mixture and dilute a volume of the clear supernatant liquid with methanol (80%) to produce a solution containing 0.010% w/v of Isradipine. Solution (2) is a 0.010% w/v solution of isradipine BPCRS in methanol (80%). Solution (3) is a 0.010% w/v solution of isradipine impurity D BPCRS in solution (2).

The chromatographic procedure described under Related substances may be used.

The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 1.5.

Calculate the content of C19H21N3O5 in the tablets using the declared content of C19H21N3O5 in isradipine BPCRS.

Storage

Isradipine Tablets should be protected from light.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed in the monograph for Isradipine.