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 90.0percent and not more than 110.0percent 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.
Identification—
A: Expel a quantity of Inhalation Aerosol,equivalent to about 12mg of isoetharine mesylate,into 2mLof methanol,dilute with methanol to 5mL,and mix:this solution responds to Identificationtest Aunder Isoetharine Inhalation Solution.
B: Expel a quantity of Inhalation Aerosol,equivalent to about 12mg of isoetharine mesylate,into a test tube,evaporate on a steam bath just to dryness,and add 50mg of powdered sodium hydroxide.Heat in a small flame to fusion,and continue heating for a few seconds longer.Cool,add about 0.5mLof water,then add a moderate excess of 3Nhydrochloric acid:starch iodate paper placed over the mouth of the test tube turns blue.
Alcohol content á611ñ— 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-mLbeaker containing 5mLof water.Slowly actuate the valve 10times.Raise the unit above the contents of the beaker,and wash the outlet with 1mLof 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 4mLof water,to a glass-stoppered graduated cylinder.Determine the alcohol content of the test solution thus prepared by the gas-liquid chromatographic procedure,2mLof dilute isopropyl alcohol (15in 100)being used as the internal standard.Calculate the alcohol content of the Inhalation Aerosol taken by the formula:
SV/W,
in which Sis the percentage (w/v)of alcohol in the test solution;Vis the total volume,in mL,of the test solution;and Wis the weight,in g,of the expelled specimen taken:between 25.9%and 35.0%(w/w)of C2H5OHis found.
Dose uniformity over the entire contents: meets the requirements for Metered-Dose Inhalersunder Aerosols,Nasal Sprays,Metered-Dose Inhalers,and Dry Powder Inhalers á601ñ.
PROCEDUREFOR DOSE UNIFORMITY—
Ferro-citrate solution and Buffer solution— Prepare as directed under Epinephrine Assay á391ñ.
Standard preparation— Dissolve an accurately weighed quantity of USP Isoetharine Hydrochloride RSin a freshly prepared sodium bisulfite solution (1in 1000),and dilute quantitatively and stepwise with the same sodium bisulfite solution as necessary to obtain a solution having a known concentration of about 34µg 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-mLportions of a freshly prepared sodium bisulfite solution (1in 500),and transfer the resulting solutions quantitatively to a 50-mLcentrifuge tube.Add 10mLof chloroform,insert the stopper,shake vigorously for 5minutes and centrifuge.Use the clear supernatant as directed in the Procedure.
Procedure— Into three separate 25-mLvolumetric flasks transfer the Test preparation,10.0mLof the Standard preparation,and 10.0mLof a freshly prepared sodium bisulfite solution (1in 1000)to provide the blank.To each flask add 0.5mLof Ferro-citrate solutionfollowed by 5mLof Buffer solution.Dilute with the sodium bisulfite solution (1in 1000)to volume,mix,and allow the color to develop for 10minutes.Concomitantly determine the absorbances with a suitable spectrophotometer,in 5-cm cells,of the solutions from the Test preparationand the Standard preparationrelative to the blank at the wavelength of maximum absorbance at about 530nm.Calculate the quantity,in µg,of C13H21NO3·CH4O3Scontained in the minimum dose taken by the formula:
10CN(335.42/275.77)(AU/AS),
in which Cis the concentration,in µg per mL,of USP Isoetharine Hydrochloride RSin the Standard preparation;Nis the number of sprays discharged to obtain the minimum recommended dose;335.42and 275.77are the molecular weights of isoetharine mesylate and isoetharine hydrochloride,respectively;and AUand ASare the absorbances of the solutions from the Test preparationand the Standard preparation,respectively.
Assay—
Mobile phase andStandard preparation— Proceed as directed in the Assayunder Isoetharine Mesylate.
Assay preparation— Weigh 1Inhalation Aerosol container with contents.Invert the container,and place the outlet tip against the bottom of a 50-mLbeaker containing 2.5mLof 0.01Nhydrochloric acid.Slowly actuate the valve about 90times (the weight of the assay specimen is approximately 5g).Raise the unit above the contents of the beaker,and wash the outlet with a few mLof 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-mLvolumetric flask with the aid of water,dilute with water to volume,and mix.
Procedure— Proceed as directed for Procedurein the Assayunder Isoetharine Mesylate.Calculate the percentage of C13H21NO3·CH4O3Sin the portion of Inhalation Aerosol taken by the formula:
0.01(335.42/275.77)(C/W)(rU/rS),
in which Wis the weight,in g,of Inhalation Aerosol taken,and the other terms are as defined therein.
Auxiliary Information— Staff Liaison:Kahkashan Zaidi,Ph.D.,Senior Scientific Associate
Expert Committee:(AER)Aerosols
USP28–NF23Page 1068
Pharmacopeial Forum:Volume No.29(1)Page 80
Phone Number:1-301-816-8269