(Ph. Eur. 11.6 update)
Beclometasone Powder for Inhalation, pre-dispensed
Action and use
Glucocorticoid.
DEFINITION
Beclometasone Inhalation Powder, pre-metered consists of Beclometasone Dipropionate or Beclometasone Dipropionate Monohydrate in microfine powder either alone or combined with a suitable carrier. The pre-metered unit is loaded into a dry-powder inhaler to generate an aerosol.
The inhalation powder, pre-metered 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 beclometasone dipropionate, C28H37ClO7
When supplied as disks, 90.0 to 110.0% of the stated amount per pre-metered unit. When supplied as capsules, 80.0 to 120.0% of the stated amount per pre-metered unit.
IDENTIFICATION
A. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as the principal peak in the chromatogram obtained with solution (2).
B. Disperse a quantity of powder, containing the equivalent of 200 μg of beclometasone dipropionate in 5 mL of 1M sodium hydroxide in a 25 mL conical flask. Add three drops of copper sulfate solution and shake. A precipitate may form which dissolves to give a clear blue solution. Heat the solution to boiling; a red precipitate is produced.
C. For products containing lactose disperse 0.25 g of the powder for inhalation in 5 mL of water. Add 5 mL of 6M ammonia and heat in a water-bath at 80° for 10 minutes. An orange-red colour is produced.
TESTS
Uniformity of delivered dose
Complies with the requirements stated under Inhalation Powders 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 of a mixture of 45 volumes of water and 55 volumes of acetonitrile to produce a solution containing the equivalent of 0.00005% w/v of beclometasone dipropionate.
(2) Dilute 10 mL of a solution containing 0.0005% w/v of beclometasone dipropionate BPCRS in methanol to 100 mL with a mixture of 45 volumes of water and 55 volumes of acetonitrile.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base-deactivated end-capped octylsilyl silica gel for chromatography (5 μm) (Lichrospher 60 RP-select B is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.3 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 240 nm.
(f) Inject 100 μL of each solution.
MOBILE PHASE
25 volumes of water and 75 volumes of methanol.
DETERMINATION OF CONTENT
Calculate the content of beclometasone dipropionate, C28H37ClO7, per delivered dose using the declared content of C28H37ClO7 in beclometasone dipropionate BPCRS. Repeat the procedure as described for pre-metered systems under Inhalation Powders, Uniformity of delivered dose.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dissolve a quantity of the mixed contents of 20 units containing the equivalent of 1.2 mg of beclometasone dipropionate in the mobile phase and dilute to 5 mL with the mobile phase.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) 0.0040% w/v each of beclometasone 17-propionate BPCRS and beclometasone 21-propionate BPCRS in the mobile phase.
(4) Dilute 1 volume of solution (2) to 20 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Lichrosorb RP18 or Lichrospher RP18 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 254 nm.
(f) Inject 100 μL of each solution.
(g) For solutions (1) and (2) allow the chromatography to proceed for twice the retention time of the principal peak.
MOBILE PHASE
Dilute 60 volumes of acetonitrile to 100 volumes with water.
When the chromatograms are recorded under the prescribed conditions, the retention time for beclometasone 17-propionate is about 6 minutes, for beclometasone 21-propionate, about 7 minutes and for beclometasone dipropionate, about 13 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to beclometasone 17-propionate and beclometasone 21-propionate is at least 1.4. If necessary adjust the concentration of acetonitrile in the mobile phase.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2%);
not more than one such secondary peak has an area greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);
the sum of the areas of all the secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (2.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).
ASSAY
Weigh and powder the contents of 20 pre-dispensed units. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dissolve a quantity of the mixed contents of the pre-dispensed unit in sufficient of the mobile phase to produce a solution containing the equivalent of 0.001% w/v of beclometasone dipropionate.
(2) 0.001% w/v of beclometasone dipropionate BPCRS in the mobile phase.
(3) 0.001% w/v each of beclometasone 17-propionate BPCRS and beclometasone 21-propionate BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to beclometasone 17-propionate and beclometasone 21-propionate is at least 1.4. If necessary adjust the concentration of acetonitrile in the mobile phase.
DETERMINATION OF CONTENT
Calculate the content of C28H37ClO7 using the declared content of C28H37ClO7 in beclometasone dipropionate BPCRS.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of beclometasone dipropionate.
