Budesonide Nebuliser Suspension

Glucocorticoid.

Budesonide Nebuliser Suspension is a suspension of Budesonide in a suitable vehicle.

The nebuliser suspension complies with the requirements stated under Preparations for Inhalation and with the following requirements.

A suitable test to determine the particle size distribution is carried out.

92.5 to 105.0% of the stated amount.

A. Dilute a quantity of the nebuliser suspension being examined with sufficient water to produce a solution containing 0.002% w/v of Budesonide and filter. The light absorption of the resulting solution, Appendix II B, in the range 200 nm to 350 nm exhibits a maximum only at 247 nm.

B. In the Assay, 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).

pH, 4.0 to 5.0, Appendix V L.

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

Prepare a mixture of 34 volumes of acetonitrile and 66 volumes of phosphate buffer solution pH 3.2 (solvent A).

(1) To a quantity of the nebuliser suspension containing 1 mg of Budesonide add 3.4 mL of acetonitrile. Mix with the aid of ultrasound, add sufficient phosphate buffer solution pH 3.2 to produce 10 mL, centrifuge and use the supernatant liquid.

(2) Dilute 1 volume of solution (1) to 200 volumes with solvent A.

(3) Dilute 1 volume of solution (2) to 10 volumes with solvent A.

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Spherisorb ODS2 is suitable).

(b) Use gradient elution and the mobile phase described below.

(c) Use a flow rate of 1 mL per minute.

(d) Use a column temperature of 50°.

(e) Use a detection wavelength of 240 nm.

(f) Inject 100 µL of each solution.

Mobile phase A    2 volumes of ethanol, 34 volumes of acetonitrile and 66 volumes of phosphate buffer solution pH 3.2.

Mobile phase B    Equal volumes of acetonitrile and phosphate buffer solution pH 3.2.

The test is not valid unless:

in the chromatogram obtained with solution (2), the resolution factor between the peaks due to epimer B and epimer A is at least 1.5;

in the chromatogram obtained with solution (3), the signal-to-noise ratio of the peaks due to epimer A and epimer B is at least 10.

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the sum of the areas of the epimer peaks in the chromatogram obtained with solution (2) (0.5%);

the sum of the areas of any secondary peaks is not greater than 3 times the sum of the areas of the epimer peaks in the chromatogram obtained with solution (2) (1.5%).

Disregard any peak with an area less than the sum of the areas of the epimer peaks in the chromatogram obtained with solution (3) (0.05%).

In the chromatogram obtained with solution (3), as described under Assay, the content of epimer A (second peak) is 40.0% to 51.0% of the sum of the areas of the two epimer peaks of budesonide.

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

Prepare a mixture of 34 volumes of acetonitrile and 66 volumes of phosphate buffer solution pH 3.2 (solvent A).

(1) To a quantity of the nebuliser suspension containing 1 mg of Budesonide add 3.4 mL of acetonitrile. Mix with the aid of ultrasound, add sufficient phosphate buffer solution pH 3.2 to produce 10 mL and filter.

(2) 0.01% w/v of budesonide BPCRS.

(3) Dilute 1 volume of solution (1) to 200 volumes.

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Spherisorb ODS2 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 50°.

(e) Use a detection wavelength of 240 nm.

(f) Inject 20 µL of each solution.

2 volumes of ethanol, 34 volumes of acetonitrile and 66 volumes of phosphate buffer solution pH 3.2.

The test is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the peaks due to epimer B and epimer A is at least 1.5.

Calculate the content of C₂₅H₃₄O₆ in the nebuliser suspension from the sum of the areas of the two budesonide epimer peaks and using the declared content of C₂₅H₃₄O₆ in budesonide BPCRS.

Budesonide Nebuliser Suspension should be protected from light.