Prolonged-release Salbutamol Tablets

Prolonged-release Salbutamol Tablets from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable unless otherwise justified and authorised.

Prolonged-release Salbutamol Tablets contain Salbutamol Sulfate. They are formulated so that the medicament is released over a period of several hours.

A suitable dissolution test is carried out to demonstrate the appropriate release of Salbutamol Sulfate. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.

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

92.5 to 107.5% of the stated amount.

A. In the Assay, the principal peak 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 sulfates, Appendix VI.

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

(1) Shake with the aid of ultrasound a quantity of the powdered tablets containing the equivalent of 20 mg of salbutamol with 5 mL of the mobile phase, add sufficient mobile phase to produce 10 mL and filter the resulting solution through a 0.45-µm membrane filter, discarding the first 1 mL of filtrate.

(2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase.

(3) Dilute 3 volumes of solution (2) to 10 volumes with mobile phase.

(4) 0.0004% w/v of salbutamol impurity B BPCRS and 0.0005% w/v of salbutamol sulfate BPCRS in the mobile phase.

(5) 0.0004% w/v of salbutamol impurity D EPCRS in the mobile phase.

(a) Use a stainless steel column (15 cm × 3.9 mm) packed with spherical end-capped octylsilyl silica gel for chromatography (5 µm) with a specific surface area of 335 m² per g, a pore size of 10 nm and a carbon loading of 11.7% (Waters Symmetry C8 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 220 nm.

(f) Inject 20 µL of each solution.

(g) Allow the chromatography to proceed for 25 times the retention time of salbutamol (retention time of salbutamol, about 1.9 minutes).

22 volumes of acetonitrile and 78 volumes of a solution containing 0.287% w/v of sodium heptanesulfonate and 0.25% w/v of potassium dihydrogen orthophosphate adjusted to pH 3.65 with 2m orthophosphoric acid.

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks due to salbutamol and salbutamol impurity B is at least 3.0.

In the chromatogram obtained with solution (1):

the area of any peak due to salbutamol impurity D is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.3%);

the sum of the areas of any secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).

Disregard any peak with an area less than one sixth of the area of the principal peak in the chromatogram obtained with solution (3) (0.05%).

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

(1) Shake with the aid of ultrasound, a quantity of the powdered tablets containing the equivalent of 20 mg of salbutamol with 5 mL of the mobile phase, add sufficient mobile phase to produce 100 mL and filter the resulting solution through a 0.45-µm membrane filter, discarding the first 10 mL of filtrate.

(2) 0.024% w/v of salbutamol sulfate BPCRS in the mobile phase.

(3) 0.0004% w/v of salbutamol impurity B BPCRS and 0.0005% w/v of salbutamol sulfate BPCRS in the mobile phase.

The chromatographic conditions described under Related substances may be used.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to salbutamol and salbutamol impurity B is at least 3.0.

Calculate the content of C₁₃H₂₁NO₃ in the tablets using the declared content of C₁₃H₂₁NO₃ in salbutamol sulfate BPCRS.

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

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