Edition: BP 2025 (Ph. Eur. 11.6 update)
Fluticasone Powder for Inhalation, pre-dispensed
Action and use
Glucocorticoid.
DEFINITION
Fluticasone Inhalation Powder, pre-metered consists of Fluticasone Propionate in microfine powder either alone or combined with a suitable carrier. The blister 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 fluticasone propionate, C25H31F3O5S
80.0 to 120.0% of the stated amount.
IDENTIFICATION
A. The light absorption, Appendix II B, in the range 210 to 300 nm of the final solution obtained in the test for Uniformity of delivered dose closely resembles that of a solution containing 0.0005% w/v of fluticasone propionate BPCRS in solvent A and exhibits a single maximum at 240 nm.
B. In the test for Uniformity of delivered dose, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).
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 in a mixture of 35 volumes of water and 65 volumes of methanol (solvent A).
(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 solvent A to produce a solution expected to contain 0.0005% w/v of Fluticasone Propionate.
(2) 0.0005% w/v of fluticasone propionate BPCRS in solvent A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Spherisorb ODS1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 239 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
15 volumes of acetonitrile, 35 volumes of 0.01M ammonium dihydrogen orthophosphate and 50 volumes of methanol adjusted to pH 3.5 with orthophosphoric acid or dilute ammonia.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (2), the symmetry factor of the principal peak is not greater than 2.5.
DETERMINATION OF CONTENT
Calculate the content of Fluticasone Propionate, C25H31F3O5S, per delivered dose using the declared content of C25H31F3O5S in fluticasone propionate 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) Shake a quantity of the powder, containing 0.5 mg of Fluticasone Propionate in 10 mL of a mixture of 7 volumes of acetonitrile, 20 volumes of water and 23 volumes of methanol and filter.
(2) Dilute 1 volume of solution (1) to 200 volumes in equal volumes of acetonitrile and water.
(3) 0.0004% w/v of fluticasone impurity D EPCRS and 0.002% w/v of fluticasone propionate BPCRS in equal volumes of acetonitrile and water.
(4) Dilute 1 volume of solution (2) to 5 volumes in equal volumes of acetonitrile and water.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Spherisorb ODS1 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 239 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
Mobile phase A 23 volumes of acetonitrile and 77 volumes of methanol.
Mobile phase B 0.01M ammonium dihydrogen orthophosphate, adjusted to pH 3.5 with acetic acid or dilute ammonia.
Equilibrate the column with a mobile phase ratio A:B of 60:40. Inject solutions (1) and (3) and start the elution isocratically with the chosen mobile phase. One minute after elution of the apex of the fluticasone propionate peak start a linear gradient elution to reach a mobile phase ratio A:B of 85:15 over a period of 10 minutes. Continue the chromatography for 10 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to fluticasone propionate and fluticasone impurity D is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the sum of the areas of any secondary peaks is not greater than 5 times the principal peak in the chromatogram obtained with solution (2) (2.5%).
Disregard any peak with an area less than the area of the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Use the average of the individual results determined in the test for Uniformity of delivered dose.
