Isoetharine Mesylate Inhalation Aerosol
» Isoetharine Mesylate Inhalation Aerosol is a solution of Isoetharine Mesylate in Alcohol in an inert propellant base. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of isoetharine mesylate (C13H21NO3·CH4O3S).
Packaging and storage Preserve in small, nonreactive, light-resistant, aerosol containers equipped with metered-dose valves and provided with oral inhalation actuators.
USP Reference standards 11
A: Expel a quantity of Inhalation Aerosol, equivalent to about 12 mg of isoetharine mesylate, into 2 mL of methanol, dilute with methanol to 5 mL, and mix: this solution responds to Identification test A under Isoetharine Inhalation Solution.
B: Expel a quantity of Inhalation Aerosol, equivalent to about 12 mg of isoetharine mesylate, into a test tube, evaporate on a steam bath just to dryness, and add 50 mg of powdered sodium hydroxide. Heat in a small flame to fusion, and continue heating for a few seconds longer. Cool, add about 0.5 mL of water, then add a moderate excess of 3 N hydrochloric acid: starch iodate paper placed over the mouth of the test tube turns blue.
Alcohol content 611 Weigh accurately a filled Inhalation Aerosol container, and record the weight. Invert the container, and place the outlet tip against the bottom of a 50-mL beaker containing 5 mL of water. Slowly actuate the valve 10 times. Raise the unit above the contents of the beaker, and wash the outlet with 1 mL of water. Collect the washings in the beaker. Dip the outlet stem in alcohol, shake to remove the solvent completely, air-dry the valve, and again weigh the Inhalation Aerosol container. Record the weight of the expelled specimen. Transfer the contents of the beaker, with the aid of 4 mL of water, to a glass-stoppered graduated cylinder. Determine the alcohol content of the test solution thus prepared by the gas-liquid chromatographic procedure, 2 mL of dilute isopropyl alcohol (15 in 100) being used as the internal standard. Calculate the alcohol content of the Inhalation Aerosol taken by the formula:
SV / Win which S is the percentage (w/v) of alcohol in the test solution; V is the total volume, in mL, of the test solution; and W is the weight, in g, of the expelled specimen taken: between 25.9% and 35.0% (w/w) of C2H5OH is found.
Dose uniformity over the entire contents: meets the requirements for Metered-Dose Inhalers under Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers 601.
Procedure for dose uniformity
Ferro-citrate solution and Buffer solution Prepare as directed under Epinephrine Assay 391.
Standard preparation Dissolve an accurately weighed quantity of USP Isoetharine Hydrochloride RS in a freshly prepared sodium bisulfite solution (1 in 1000), and dilute quantitatively and stepwise with the same sodium bisulfite solution as necessary to obtain a solution having a known concentration of about 34 µg per mL.
Test preparation Discharge the minimum recommended dose into the sampling apparatus and detach the inhaler as directed. Rinse the apparatus (filter and interior) with two 5.0-mL portions of a freshly prepared sodium bisulfite solution (1 in 500), and transfer the resulting solutions quantitatively to a 50-mL centrifuge tube. Add 10 mL of chloroform, insert the stopper, shake vigorously for 5 minutes and centrifuge. Use the clear supernatant as directed in the Procedure.
Procedure Into three separate 25-mL volumetric flasks transfer the Test preparation, 10.0 mL of the Standard preparation, and 10.0 mL of a freshly prepared sodium bisulfite solution (1 in 1000) to provide the blank. To each flask add 0.5 mL of Ferro-citrate solution followed by 5 mL of Buffer solution. Dilute with the sodium bisulfite solution (1 in 1000) to volume, mix, and allow the color to develop for 10 minutes. Concomitantly determine the absorbances with a suitable spectrophotometer, in 5-cm cells, of the solutions from the Test preparation and the Standard preparation relative to the blank at the wavelength of maximum absorbance at about 530 nm. Calculate the quantity, in µg, of C13H21NO3·CH4O3S contained in the minimum dose taken by the formula:
10CN(335.42 / 275.77)(AU / AS)in which C is the concentration, in µg per mL, of USP Isoetharine Hydrochloride RS in the Standard preparation; N is the number of sprays discharged to obtain the minimum recommended dose; 335.42 and 275.77 are the molecular weights of isoetharine mesylate and isoetharine hydrochloride, respectively; and AU and AS are the absorbances of the solutions from the Test preparation and the Standard preparation, respectively.
Mobile phase and Standard preparation Proceed as directed in the Assay under Isoetharine Mesylate.
Assay preparation Weigh 1 Inhalation Aerosol container with contents. Invert the container, and place the outlet tip against the bottom of a 50-mL beaker containing 2.5 mL of 0.01 N hydrochloric acid. Slowly actuate the valve about 90 times (the weight of the assay specimen is approximately 5 g). Raise the unit above the contents of the beaker, and wash the outlet with a few mL of water. Collect the washings in the beaker. Dip the outlet stem in alcohol, shake to remove the solvent completely, air-dry the valve, and then again weigh the Inhalation Aerosol container. Record the weight of the expelled specimen. Transfer the contents of the beaker to a 100-mL volumetric flask with the aid of water, dilute with water to volume, and mix.
Procedure Proceed as directed for Procedure in the Assay under Isoetharine Mesylate. Calculate the percentage of C13H21NO3·CH4O3S in the portion of Inhalation Aerosol taken by the formula:
0.01(335.42 / 275.77)(C / W)(rU / rS)in which W is the weight, in g, of Inhalation Aerosol taken; and the other terms are as defined therein.
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USP35NF30 Page 3567Pharmacopeial Forum: Volume No. 29(1) Page 80