- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Ipratropium Nebuliser Solution |
Ipratropium Nebuliser Solution is a solution of Ipratropium Bromide in Water for Injections and may contain sodium chloride.
The nebuliser solution complies with the requirements stated under Preparations for Inhalation and with the following requirements.
95.0 to 110.0% of the stated amount.
A. Evaporate a volume of the nebuliser solution containing 1.5 mg of Ipratropium Bromide to dryness on a water bath. Shake the residue with 5 mL of methanol and filter (Whatman GF/C is suitable). Evaporate the filtrate to dryness on a water bath and dry the residue at room temperature at a pressure of 1 kPa for 15 minutes. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with a spectrum prepared from a mixture of 5 mg of ipratropium bromide BPCRS and 45 mg of sodium chloride dissolved in the minimum quantity of water, evaporated to dryness on a water bath and treated in a similar manner to the substance being examined beginning at the words "Shake the residue with 5 mL of methanol,……".
B. To a quantity of the nebuliser solution containing 0.5 mg of Ipratropium Bromide 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.
pH, 3.0 to 4.0, Appendix V L.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a quantity of the nebuliser solution, if necessary, with sufficient 0.001m hydrochloric acid to produce a solution containing 0.02% w/v of Ipratropium Bromide.
(2) Dilute 1 volume of solution (1) to 200 volumes with 0.001m 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) Stainless steel column (12.5 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm)(Columbus C8 is suitable).
(b) Isocratic elution using the mobile phase described below.
(c) Flow rate of 0.5 mL per minute.
(d) Ambient column temperature.
(e) Detection wavelength of 210 nm.
(f) Injection volume of 20 µL for each solution.
For solution (1) allow the chromatography to proceed for 6 times the retention time of ipratropium (retention time of ipratropium, about 11 minutes).
A mixture of 4 volumes of freshly distilled triethylamine, 50 volumes of propan-2-ol R1, 100 volumes of acetonitrile R1 and 850 volumes of a 0.1% w/v solution of sodium methanesulfonate previously adjusted to pH 3.0 with 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 3 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
Disregard any peak with an area less than 0.2 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
The osmolality of the solution is 245 mosmol/kg to 299 mosmol/kg, Appendix V N.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a quantity of the nebuliser solution, if necessary, with sufficient 0.001m hydrochloric acid to produce a solution containing 0.02% w/v of Ipratropium Bromide.
(2) 0.02% w/v of ipratropium bromide BPCRS in 0.001m 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.
The chromatographic procedure described under Related substances 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 1.0.
Calculate the content of C20H30NO3Br,H2O in the solution using the declared content of C20H30NO3Br,H2O in ipratropium bromide BPCRS.
Ipratropium Nebuliser Solution should be stored protected from light in a sealed container.
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).