Isosorbide Dinitrate Sublingual Tablets

General Notices

Action and use

Nitric oxide analogue; treatment of angina pectoris.

Definition

Isosorbide Dinitrate Sublingual Tablets contain Diluted Isosorbide Dinitrate.

caution Undiluted isosorbide dinitrate can be exploded by percussion or excessive heat. Appropriate precautions should be exercised and only exceedingly small amounts should be isolated.
The sublingual tablets comply with the requirements stated under Oromucosal Preparations and with the following requirements.

Content of isosorbide dinitrate, C6H8N2O8

90.0 to 110.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Extract a quantity of the powdered tablets containing 2 mg of isosorbide dinitrate with 1 mL of ether and centrifuge.
(2) Prepare solution (2) in the same manner but use isosorbide dinitrate BPCRS in place of the powdered tablets.
chromatographic conditions
(a) Use as the coating silica gel.
(b) Use the mobile phase as described below.
(c) Apply 20 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry it in a current of air, spray with diphenylamine solution R1 and irradiate for 15 minutes with ultraviolet light (254 and 365 nm).
mobile phase

toluene.

confirmation

The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

B. Shake a quantity of the powdered tablets containing 50 mg of Isosorbide Dinitrate with warm sulfuric acid (50%) containing a trace of diphenylamine. An intense blue colour is produced.

Tests

Inorganic nitrates

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

(1) Shake a quantity of the powdered tablets containing 0.1 g of Isosorbide Dinitrate with 5 mL of ethanol (96%) and filter.
(2) Dissolve 10 mg of potassium nitrate in 1 mL of water and dilute to 100 mL with ethanol (96%).
chromatographic conditions
(a) Use as the coating silica gel H.
(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 thoroughly dry it in a current of air until the acetic acid is completely removed. Spray copiously with freshly prepared potassium iodide and starch solution. Expose the plate to ultraviolet light (254 nm) for 15 minutes. Examine in daylight.
mobile phase

15 volumes of glacial acetic acid, 30 volumes of acetone and 60 volumes of toluene.

limits

In the chromatogram obtained with solution (1) any spot corresponding to potassium nitrate is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%, calculated as potassium nitrate).

Isosorbide 5-nitrate and isosorbide 2-nitrate

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add 20 mL of the mobile phase to a quantity of the powdered tablets containing 25 mg of Isosorbide Dinitrate, mix with the aid of ultrasound for 15 minutes and dilute to 25 mL with the same solvent. Filter through a glass-fibre filter (Whatman GF/C is suitable) and use the filtrate.
(2) 0.0005% w/v of isosorbide 2-nitrate BPCRS in the mobile phase.
(3) 0.0005% w/v of isosorbide mononitrate BPCRS in the mobile phase.
(4) 0.005% w/v each of isosorbide dinitrate BPCRS and isosorbide 2-nitrate BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with aminopropylsilyl silica gel for chromatography (10 µm) (Lichrosorb NH2 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 215 nm.
(f) Inject 20 µL of each solution.
mobile phase

15 volumes of absolute ethanol and 85 volumes of 2,2,4-trimethylpentane.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks corresponding to isosorbide dinitrate and isosorbide 2-nitrate is at least 6.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to isosorbide 2-nitrate is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any peak corresponding to isosorbide 5-nitrate is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.5%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) To a quantity of the powdered tablets containing 25 mg of Isosorbide Dinitrate add 20 mL of the mobile phase mix with the aid of ultrasound for 15 minutes and dilute to 25 mL with the same solvent. Filter through a glass-fibre filter (Whatman GF/C is suitable) and dilute 1 volume to 10 volumes with the mobile phase.
(2) To a quantity of isosorbide dinitrate BPCRS containing 25 mg of Isosorbide Dinitrate add 20 mL of the mobile phase mix with the aid of ultrasound for 15 minutes and dilute to 25 mL with the mobile phase. Filter through a glass-fibre filter (Whatman GF/C is suitable) and dilute 1 volume to 10 volumes with the mobile phase.
(3) 0.005% w/v each of isosorbide dinitrate BPCRS and isosorbide 2-nitrate BPCRS in the mobile phase.
chromatographic conditions

The chromatographic procedure described under Isosorbide 5-nitrate and isosorbide 2-nitrate may be used but using a detection wavelength of 230 nm.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks corresponding to isosorbide dinitrate and isosorbide 2-nitrate is at least 6.0.

determination of content

Calculate the content of C6H8N2O8 in the tablets from the chromatograms obtained and using the declared content of C6H8N2O8 in isosorbide dinitrate BPCRS.

Labelling

The label states that the tablets should be placed under the tongue and allowed to dissolve slowly.