- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Beclometasone Pressurised Inhalation |
Beclometasone Pressurised Inhalation prepared using different propellant gases, whilst complying with the requirements of the monograph, may not necessarily be interchangeable.
Glucocorticoid.
Beclometasone Pressurised Inhalation is a solution or suspension of Anhydrous Beclometasone Dipropionate in a suitable liquid in a suitable pressurised container.
The pressurised inhalation complies with the requirements stated under Preparations for Inhalation and with the following requirements.
80.0 to 120.0% of the amount stated to be delivered by actuation of the valve.
A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of beclometasone dipropionate (2) (RS 379). Examine the substance as a dispersion in potassium bromide prepared in the following manner. Discharge the container a sufficient number of times, under conditions of very low relative humidity (less than 5%), into a mortar to obtain 2 mg of Anhydrous Beclometasone Dipropionate. Heat at 110° for 2 hours at a pressure of 2 kPa, cool, grind the residue thoroughly with 0.1 g of potassium bromide, add a further 0.2 g of potassium bromide and mix thoroughly.
B. In the Assay, the principal peak in the chromatogram obtained with solution (1) corresponds to the peak due to beclometasone dipropionate in the chromatogram obtained with solution (2).
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in acetone.
(1) Discharge the container into a small, dry flask a sufficient number of times to obtain 0.5 mg of Anhydrous Beclometasone Dipropionate and dissolve the residue in 2 mL of acetone. Evaporate the solution to a volume such that the whole solution can be applied to the plate.
(2) 0.1% w/v of beclometasone dipropionate BPCRS.
(3) Dilute 1 volume of solution (2) to 2 volumes.
(4) Dilute 1 volume of solution (2) to 4 volumes.
(a) Use as the coating silica gel G.
(b) Use the mobile phase described below.
(c) Apply separately to the plate the whole of solution (1) and 10 µL of each of solutions (2), (3) and (4).
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, spray with alkaline tetrazolium blue solution and heat at 50° for 5 minutes. Cool and spray again with alkaline tetrazolium blue solution.
3 volumes of methanol and 97 volumes of 1,2-dichloroethane.
In the chromatogram obtained with solution (1):
any secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (2%);
not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3) (1%);
not more than two such spots are more intense than the spot in the chromatogram obtained with solution (4) (0.5%).
Disregard any spot with an Rf value of more than 0.85.
Carry out the test for aerodynamic assessment of fine particles, Appendix XII C7, using Apparatus A with 7 mL of methanol in the upper impingement chamber and 30 mL of methanol in the lower impingement chamber but determining the content of active ingredient as described below. Use methanol to wash the coupling tube, E, and transfer the combined solution and washings in the lower impingement chamber to a flask containing sufficient testosterone propionate BPCRS (internal standard) in methanol that, on dilution to volume with appropriate amounts of water and methanol, the final solution contains 0.00015% w/v each of testosterone propionate and beclometasone dipropionate in the methanol-water mixture in the proportions 70:30 by volume.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) 0.00015% w/v each of testosterone propionate BPCRS and beclometasone dipropionate BPCRS in the mobile phase.
(2) The diluted solution from the lower impingement chamber.
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use a column temperature of 50°.
(e) Use a detection wavelength of 239 nm.
(f) Inject 20 µL of each solution.
70 volumes of methanol and 30 volumes of water, adjusted if necessary so that the resolution factor between the peaks due to beclometasone dipropionate and testosterone propionate is at least 2.0.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 2.0.
Calculate the amount of beclometasone dipropionate, C28H37ClO7, delivered to the lower impingement chamber per actuation of the valve using the declared content of C28H37ClO7 in beclometasone dipropionate BPCRS. For pressurised inhalations containing 50 µg and 100 µg of Anhydrous Beclometasone Dipropionate, not less than 35% of the average amount of beclometasone delivered per actuation of the valve, calculated as the average of the three results determined in the Assay, is deposited in the lower impingement chamber. For pressurised inhalations containing 200 µg and 250 µg of Anhydrous Beclometasone Dipropionate, not less than 25% of the average amount of beclometasone dipropionate delivered per actuation of the valve, calculated as the average of the three results determined in the Assay, is deposited in the lower impingement chamber.
Determine the content of active ingredient delivered by the first 10 successive combined actuations of the valve after priming. Carry out the procedure for Content of active ingredient delivered by actuation of the valve described under Pressurised Inhalations, beginning at the words 'Remove the pressurised container from the actuator ...' and ending at the words '... to the volume specified in the monograph', using 35 mL of methanol in the vessel. Transfer the combined solution and washings obtained from the set of 10 combined actuations to a flask containing sufficient testosterone propionate BPCRS (internal standard) in methanol that, on dilution to volume with appropriate amounts of water and methanol, the final solution contains 0.00015% w/v each of testosterone propionate and beclometasone dipropionate in the methanol-water mixture in the proportions 70:30 by volume (solution A). Determine the content of active ingredient in the 10 combined actuations using the following method of analysis.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Solution A.
(2) 0.00015% w/v of beclometasone dipropionate BPCRS in the mobile phase.
(3) 0.00015% w/v each of testosterone propionate BPCRS and beclometasone dipropionate BPCRS in the mobile phase.
The chromatographic conditions described under Deposition of the emitted dose may be used.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 2.0.
Calculate the average content of C28H37ClO7 delivered by a single actuation of the valve using the declared content of C28H37ClO7 in beclometasone dipropionate BPCRS.
Determine the content of active ingredient a second and third time by repeating the procedure on the middle 10 and on the last 10 successive combined actuations of the valve, as estimated from the number of deliveries available from the container as stated on the label. For each of the three determinations the average content of C28H37ClO7 delivered by a single actuation of the valve is within the limits stated under Content of beclometasone dipropionate.