Salbutamol Powder for Inhalation, metered-dose powder inhalers
Action and use
Beta2-adrenoceptor agonist; bronchodilator.
DEFINITION
Salbutamol Inhalation Powder consists of Salbutamol Sulfate in microfine powder either alone or combined with a suitable carrier. It is administered by a dry-powder inhaler.
The inhalation powder complies with the requirements stated under Preparations for Inhalation and with the following requirements.
PRODUCTION
The size of aerosol particles to be inhaled is controlled so that a consistent portion is deposited in the lungs. The fine-particle characteristics of preparations for inhalation are determined using the method described in Appendix XII C7.
Preparations for inhalation: Aerodynamic Assessment of Fine Particles. The test and limits should be agreed with the competent authority.
The water content is controlled to ensure the performance of the product as justified and authorised by the competent authority.
Content of salbutamol, C13H21NO3
80.0 to 120.0% of the stated amount.
IDENTIFICATION
A. In the Assay, record the UV spectrum of the principal peak in the chromatograms obtained with solutions (1) and (2) with a diode array detector in the range of 210 to 400 nm.
The UV spectrum of the principal peak in the chromatogram obtained with solution (1) is concordant with that of the peak in the chromatogram obtained with solution (2); the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
B. Dissolve a quantity of the inhalation powder containing the equivalent of 4 mg of salbutamol with 5 mL of water. The resulting solution yields reaction A characteristic of sulfates, Appendix VI.
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Dissolve a quantity of the inhalation powder in sufficient mobile phase to produce a solution containing the equivalent of 0.02% w/v of salbutamol and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes and further dilute 1 volume of this solution to 5 volumes.
(3) 0.02% w/v of salbutamol for peak identification EPCRS.
(4) 0.02% w/v of salbutamol impurity standard BPCRS.
(5) 0.00004% w/v of each of salbutamol sulfate BPCRS and salbutamol impurity B BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octylsilyl silica gel for chromatography (5 μm) (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) For solution (1), allow the chromatography to proceed for 25 times the retention time of salbutamol.
MOBILE PHASE
22 volumes of acetonitrile R1 and 78 volumes of a solution containing 0.287% w/v of sodium heptanesulfonate and 0.25% w/v of potassium dihydrogen orthophosphate previously adjusted to pH 3.7 with 2M orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to salbutamol and impurity B is at least 3.0.
CALCULATION OF IMPURITIES
For each impurity, use the concentration of salbutamol in solution (2).
For the reporting threshold, use the concentration of salbutamol in solution (2).
For peak identification, use solutions (3) and (4).
Salbutamol retention time: about 3 minutes.
Relative retention: impurity B, about 1.4; impurity D, about 2.7; impurity F, about 6.3.
Correction factor: impurity D, multiply by 0.5.
LIMITS
— impurity F: not more than 0.8%;
— impurity D: not more than 0.3%;
— unspecified impurities: for each impurity, not more than 0.2%;
— total impurities: not more than 2.0%;
— reporting threshold: 0.1%.
Uniformity of delivered dose
Complies with the requirements for Inhalation Powders stated under Preparations for Inhalation using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Collect single doses of the preparation being examined using the procedure described under Inhalation Powders, Uniformity of delivered dose and dissolve the collected dose in sufficient water to produce a solution containing the equivalent of 0.0001% w/v of salbutamol.
(2) 0.00012% w/v of salbutamol sulfate BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used, excluding (g).
DETERMINATION OF CONTENT
Calculate the content of salbutamol, C13H21NO3, per delivered dose using the declared content of C13H21NO3 in salbutamol sulfate BPCRS. Repeat the procedure as described for reservoir systems under Inhalation Powders, Uniformity of delivered dose.
ASSAY
Where the label states delivered dose, use the average of the individual results determined in the test for Uniformity of delivered dose.
Where the label states metered dose, carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dissolve a quantity of the inhalation powder in sufficient water to produce a solution containing the equivalent of 0.0001% w/v of salbutamol.
(2) 0.00012% w/v of salbutamol sulfate BPCRS in water.
(3) 0.0001% w/v of salbutamol sulfate BPCRS and 0.0001% w/v of salbutamol impurity B BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used, excluding (g).
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to salbutamol and impurity B is at least 3.0.
DETERMINATION OF CONTENT
Calculate the content of salbutamol, C13H21NO3, using the declared content of C13H21NO3 in salbutamol sulfate BPCRS.
LABELLING
The label states the content of active ingredient in terms of the equivalent metered dose.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B, C, D, E, F, G, H, I, J and P listed under Salbutamol Sulfate
