- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Ipratropium Powder for Inhalation |
Ipratropium Powder for Inhalation consists of hard gelatin capsules containing Ipratropium Bromide admixed with Glucose. The contents of the capsules are in powder of a suitable fineness.
The powder for inhalation complies with the requirements stated under Preparations for Inhalation and the contents of the capsules comply with the following requirements.
90.0 to 110.0% of the stated amount.
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Vigorously shake for 2 minutes a quantity of the contents of the capsules containing 0.1 g of Ipratropium Bromide with 1 mL of methanol, centrifuge and use the supernatant.
(2) 0.1% w/v of ipratropium bromide BPCRS in a saturated solution of glucose.
(3) 0.0005% w/v of tropic acid in a saturated solution of glucose.
(a) Use as the coating silica gel GF254 (Merck HPTLC plates are suitable).
(b) The mobile phase is a mixture of 1 volume of formic acid, 3 volumes of water, 18 volumes of ethanol and 18 volumes of dichloromethane.
(c) Develop to 5 cm.
(d) Application volume of 10 µL for each solution.
(e) Remove the plate, dry for 15 minutes at 60°, spray with potassium iodobismuthate solution, dry briefly in a current of air and spray with a 5% w/v solution of sodium nitrite.
The principal spot in the chromatogram obtained with solution (1) corresponds in position, size and intensity to that in the chromatogram obtained with solution (2).
B. Disperse a quantity of the contents of the capsules containing the equivalent of 0.3 mg of bromide ion in 0.5 mL of water add 75 mg of lead dioxide and 0.25 mL of acetic acid, shake gently and allow to stand for 5 minutes. Add one drop to a strip of filter paper previously impregnated with decolorised fuchsin solution, a characteristic violet colour develops.
C. In the Assay, the principal peak in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Vigorously shake for 2 minutes a quantity of the contents of the capsules containing 0.1 g of Ipratropium Bromide with 1 mL of methanol, centrifuge and use the supernatant.
(2) Dilute 1 volume of solution (1) to 200 volumes with a saturated solution of glucose.
(3) 0.0005% w/v of tropic acid in a saturated solution of glucose.
(a) Use as the coating substance silica gel GF254 (Merck HPTLC plates are suitable).
(b) The mobile phase is a mixture of 1 volume of formic acid, 3 volumes of water, 18 volumes of ethanol and 18 volumes of dichloromethane.
(c) Develop to 5 cm.
(d) Application volume of 10 µL for each solution.
(e) Remove the plate, dry for 15 minutes at 60°, spray with potassium iodobismuthate solution, dry briefly in a current of air and spray with a 5% w/v solution of sodium nitrite.
In the chromatogram obtained with solution (1):
any spot corresponding to tropic acid is not more intense than the spot in the chromatogram obtained with solution (2)(0.5%);
any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2)(0.5%).
B. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the contents of the capsules solution with sufficient mobile phase to produce a solution containing 0.02% w/v of Ipratropium Bromide.
(2) Dilute 1 volume of solution (1) to 200 volumes with mobile phase.
(3) 0.005% w/v of 8s-isopropyl-3b-hydroxytropanium bromide BPCRS and 0.005% w/v of ipratropium bromide BPCRS in 0.001m hydrochloric acid.
(a) A stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm), (Lichrospher 60 RP-select B is suitable).
(b) Isocratic elution using the mobile phase described below.
(c) Flow rate of 2 mL per minute.
(d) Detection wavelength of 210 nm.
(e) Injection volume of 20 µL for each solution.
A mixture of 3 volumes of acetonitrile for chromatography and 25 volumes of a 0.1% w/v solution of sodium methanesulfonate in 0.05m orthophosphoric acid.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 1.0.
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 such peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak with an area less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the contents of the capsules with sufficient 0.01m hydrochloric acid to produce a solution containing 0.0040% w/v of Ipratropium Bromide, filter and use the filtrate.
(2) 0.004% w/v of ipratropium bromide BPCRS in 0.01m hydrochloric acid.
(3) 0.005% w/v of 8s-isopropyl-3b-hydroxytropanium bromide BPCRS and 0.005% w/v of ipratropium bromide BPCRS in 0.001m hydrochloric acid.
(a) A stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm), (Lichrospher 60 RP-select B is suitable).
(b) Isocratic elution using the mobile phase described below.
(c) Flow rate of 2 mL per minute.
(d) Detection wavelength of 210 nm.
(e) Injection volume of 20 µL for each solution.
A mixture of 27 volumes of acetonitrile for chromatography and 100 volumes of a 0.25% w/v solution of sodium heptanesulfonate monohydrate in water adjusted to pH 3.2 with 0.05m orthophosphoric acid.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 1.0.
Calculate the content of C20H30NO3Br,H2O in the powder for inhalation using the declared content of C20H30BrNO3,H2O in ipratropium bromide BPCRS.
The impurities limited by the requirements of this monograph include.
A. (1R,3r,5S,8r)-3-hydroxy-8-methyl-8-(1-methylethyl)-8-azoniabicyclo[3.2.1]octane,
B. (1R,3r,5S,8s)-3-[[(2RS)-3-hydroxy-2-phenylpropanoyl]oxy]-8-methyl-8-(1-methylethyl)-8- azoniabicyclo[3.2.1]octane,
C. R = CH2-OH, R′ = H: (2RS)-3-hydroxy-2-phenylpropanoic acid (dl-tropic acid),
D. R + R′ = CH2: 2-phenylpropenoic acid (atropic acid).