Aminophylline Tablets

General Notices

Action and use

Non-selective phosphodiesterase inhibitor; treatment of reversible airways obstruction.

Definition

Aminophylline Tablets contain Aminophylline or Aminophylline Hydrate.

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

Content of theophylline, C7H8N4O2

81.4 to 90.0% of the stated amount of aminophylline.

Content of ethylenediamine, C2H8N2

13.5 to 15.0% of the stated amount of aminophylline.

Identification

A. Shake a quantity of the powdered tablets containing the equivalent of 0.5 g of aminophylline with 20 mL of water, filter, add to the filtrate with constant stirring 1 mL of 2m hydrochloric acid, allow to stand for a few minutes and again filter. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of theophylline (RS 333).
B. Shake a quantity of the powdered tablets containing the equivalent of 0.25 g of aminophylline with 5 mL of water and filter. To 2 mL of the filtrate add 2 mL of a 1% w/v solution of copper(ii) sulfate and shake. A purplish blue colour is produced.

Tests

Dissolution of theophylline

Comply with the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of phosphate buffer pH 7.0, at a temperature of 37°, as the medium.
procedure

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.

(1) Use the filtered dissolution medium, diluted with phosphate buffer pH 7.0, if necessary to produce a solution expected to contain 0.001% w/v of theophylline.
(2) 0.001% w/v solution of theophylline BPCRS in phosphate buffer pH 7.0.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with particles of silica the surface of which has been modified with chemically-bonded phenyl groups (5 µm) (Apex Phenyl is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 273 nm.
(f) Inject 20 µL of each solution.
mobile phase

45 volumes of methanol and 55 volumes of water.

determination of content

Calculate the total content of theophylline, C7H8N4O2, in the medium using the declared content of C7H8N4O2 in theophylline BPCRS.

Related substances

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

(1) Shake a quantity of the powdered tablets containing the equivalent of 0.25 g of aminophylline with 50 mL of the mobile phase and add sufficient of the mobile phase to produce 100 mL.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase. Further dilute 1 volume of this solution to 5 volumes with the mobile phase.
(3) Dissolve 10 mg of theobromine (impurity G) in the mobile phase, add 5 mL of solution (1) and dilute to 100 mL with the mobile phase. Dilute 1 volume of this solution to 10 volumes with the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.0 mm) packed with octadecylsilyl silica gel for chromatography (7 µm) (Lichrosorb RP18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 272 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for 3.5 times the retention time of theophylline.
mobile phase

7 volumes of acetonitrile and 93 volumes of a 0.136% w/v solution of sodium acetate containing 0.50% v/v of glacial acetic acid.

When the chromatograms are recorded under the prescribed conditions the retention time relative to theophylline (about 6 minutes) is: impurity G, about 0.6.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity G and theophylline is at least 2.0.

limits

In the chromatogram obtained with solution (1):

the sum of the areas of all the secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%).

Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

Assay

For theophylline

Weigh and powder 20 tablets. Shake a quantity of the powder containing the equivalent of 80 mg of aminophylline with a mixture of 20 mL of 0.1m sodium hydroxide and 60 mL of water for 10 minutes, add sufficient water to produce 200 mL, mix and filter. Dilute 5 mL of the filtrate to 250 mL with 0.01m sodium hydroxide and measure the absorbance of the resulting solution at the maximum at 275 nm, Appendix II B. Calculate the content of C7H8N4O2 taking 650 as the value of A (1%, 1 cm) at the maximum at 275 nm.

For ethylenediamine

Weigh and powder 20 tablets. Shake a quantity of the powder containing the equivalent of 0.3 g of aminophylline with 20 mL of water, heat to 50° for 30 minutes and titrate with 0.05m sulfuric acid VS, using bromocresol green solution as indicator, until the colour changes from blue to green. Each mL of 0.05m sulfuric acid VS is equivalent to 3.005 mg of C2H8N2.

Storage

Aminophylline Tablets should be kept in an airtight container and protected from light.

Labelling

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

Impurities

The impurities limited by the requirements of this monograph include those listed under Aminophylline.