Salbutamol Tablets

Definition

 

Salbutamol Tablets contain Salbutamol Sulphate.

 

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

 

Content of salbutamol, C13H21NO3

 

92.5 to 107.5% of the stated amount.

 

Identification

 

A.   Carry out the method described under Related substances applying separately to the plate 2 µl of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing the equivalent of 10 mg of salbutamol with 10 ml of methanol  (80%) and filter. Solution (2) contains 0.12% w/v of salbutamol sulphate BPCRS. 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 the equivalent of 2.5 mg of salbutamol with 50 ml of a 2% w/v solution of sodium tetraborate, add 1 ml of a 3% w/v solution of 4-aminophenazone, 10 ml of a 2% w/v solution of potassium hexacyanoferrate(III) and 10 ml of chloroform, shake and allow to separate. An orange-red colour is produced in the chloroform layer.

 

C.    Shake a quantity of the powdered tablets containing the equivalent of 4 mg of salbutamol with 10 ml of water  and filter. The filtrate yields the reactions characteristic of sulphates, Appendix VI.

 

Related substances

 

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 3 volumes of 13.5M ammonia, 18 volumes of water , 35 volumes of ethyl acetate, 45 volumes of propan-2-ol  and 50 volumes of 4-methylpentan-2-one as the mobile phase but allowing the solvent front to ascend 18 cm above the line of application. Apply separately to the plate 10 µl of each of the following solutions. For solution (1) shake a quantity of the tablets containing the equivalent of 48 mg of salbutamol with 60 ml of ethanol  (50%) for 30 minutes, filter, evaporate to dryness using a rotary evaporator and gentle heat and dissolve the residue in 2 ml of water ; if the residue is coloured, pass the final solution through a column (3 cm 6 mm) packed with activated acid aluminium oxide (Brockmann Grade I is suitable). Solution (2) contains 0.058% w/v of salbutamol sulphate BPCRS in water . Solution (3) contains 0.022% w/v of salbutamol sulphate BPCRS in water . After removal of the plate, allow it to dry in air until the solvent has evaporated and spray with a 0.1% w/v solution of 3-methylbenzothiazolin-2-one hydrazone hydrochloride in methanol  (90%) followed by a 2% w/v solution of potassium hexacyanoferrate(III) in a mixture of 1 volume of 18M ammonia and 3 volumes of water  and spray again with the solution of methylbenzothiazolinone hydrazone hydrochloride. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (2%) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3) (0.75%).

 

Uniformity of content

 

Tablets containing the equivalent of 2 mg or less of salbutamol comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III A, using the following solutions. Solution (1) contains 0.060% w/v of 2-tert-butylamino-1-(4-hydroxy-3-methylphenyl)ethanol  sulphate BPCRS and 0.060% w/v of salbutamol sulphate BPCRS in the mobile phase. Solution (2) contains 0.0024% w/v of salbutamol sulphate BPCRS in water . For solution (3) add 50 ml of water  to one tablet, shake for 1 hour, add sufficient water  to produce 100 ml, mix, centrifuge and use the supernatant liquid.

 

The chromatographic procedure may be carried out using (a) a stainless steel column (20 cm 5 mm) packed with spherical particles of silica, 5 µm in diameter, the surface of which has been modified with chemically-bonded nitrile groups (Spherisorb CN is suitable), (b) as the mobile phase with a flow rate of 2.0 ml per minute a mixture of 65 volumes of water , 30 volumes of 0.05M ammonium acetate and 5 volumes of propan-2-ol , the pH of the mixture being adjusted to 4.5 with glacial acetic acid, and (c) a detection wavelength of 276 nm.

 

Calculate the content of C13H21NO3 in each tablet using the declared content of C13H21NO3 in salbutamol sulphate BPCRS. The test is not valid unless the resolution factor  between the two principal peaks in the chromatogram obtained with solution (1) is at least 1.5.

 

Assay

 

For tablets containing the equivalent of more than 2 mg of salbutamol

 

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.048% w/v of 2-tert-butylamino-1-(4-hydroxy-3-methylphenyl)ethanol  sulphate BPCRS and 0.048% w/v of salbutamol sulphate BPCRS in methanol  (10%). Solution (2) contains 0.048% w/v of salbutamol sulphate BPCRS in water . For solution (3) shake 10 tablets with 100 ml of water  for 1 hour, add sufficient water  to produce a solution containing the equivalent of 0.040% w/v of salbutamol, mix, centrifuge and use the supernatant liquid.

 

The chromatographic procedure described under Uniformity of content may be used.

 

The test is not valid unless the resolution factor  between the two principal peaks in the chromatogram obtained with solution (1) is at least 1.5.

 

Calculate the content of C13H21NO3 using the declared content of C13H21NO3 in salbutamol sulphate BPCRS.

 

For tablets containing the equivalent of 2 mg or less of salbutamol

 

Use the average of the 10 individual results obtained in the test for Uniformity of content.

 

Labelling

 

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