Epinephrine Inhalation Aerosol
»Epinephrine Inhalation Aerosol is a solution of Epinephrine in propellants and Alcohol prepared with the aid of mineral acid in a pressurized container.It contains not less than 90.0percent and not more than 115.0percent of the labeled amount of epinephrine (C9H13NO3).
Packaging and storage— Preserve in small,nonreactive,light-resistant aerosol containers equipped with metered-dose valves and provided with oral inhalation actuators.
Identification— Place 10mLof water in a small beaker,and deliver 2sprays from the Inhalation Aerosol under the surface of the water,actuating the valve by pressing the tip against the bottom of the beaker.To 5mLof the solution add 1drop of dilute sulfuric acid (1in 200),add 0.5mLof 0.1Niodine,allow to stand for 5minutes,and add 1mLof 0.1Nsodium thiosulfate:a red-brown color is produced.
Delivered dose uniformity over the entire contents: meets the requirements for Metered-Dose Inhalersunder Aerosols,Nasal Sprays,Metered-Dose Inhalers,and Dry Powder Inhalers á601ñ.
PROCEDURE FOR DOSE UNIFORMITY—
Ferro-citrate solution and Buffer solution—Prepare as directed under Epinephrine Assay á391ñ.
Standard preparation— Dissolve an accurately weighed quantity of USP Epinephrine Bitartrate RSin a freshly prepared sodium bisulfite solution (1in 500),and dilute quantitatively and stepwise with the same sodium bisulfite solution as necessary to obtain a solution having a known concentration of about 18µg 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 four 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 1minute,and centrifuge for 5minutes.Use the clear supernatant as directed in the Procedure.
Procedure— Into three separate flasks,transfer the Test preparation,20.0mLof the Standard preparation,and 20.0mLof water to provide the blank.To each flask add 100µLof Ferro-citrate solutionand 1.0mLof Buffer solution,and mix.Concomitantly determine the absorbances with a suitable spectrophotometer,in 5-cm cells,of the solutions from the Test preparationand the Standard preparation,at the wavelength of maximum absorbance at about 530nm,against the blank.Calculate the quantity,in µg,of C9H13NO3contained in the minimum dose taken by the formula:
(183.20/333.29)(20CN)(AU/AS),
in which Cis the concentration,in µg per mL,of USP Epinephrine Bitartrate RSin the Standard preparation;Nis the number of sprays discharged to obtain the minimum recommended dose;183.20and 333.29are the molecular weights of epinephrine and epinephrine bitartrate,respectively;and AUand ASare the absorbances of the solutions from the Test preparationand the Standard preparation,respectively.
Assay— Weigh the Inhalation Aerosol,chill to a temperature below -30,remove the valve by suitable means,and allow the Inhalation Aerosol to warm slowly to room temperature to expel the more volatile propellant fractions.Transfer the residues in the aerosol container and valve to a 125-mLseparator with the aid of six 5-mLportions of dilute sulfuric acid (1in 1000),and extract the solution with three 25-mLportions of chloroform.Proceed as directed in the Assayunder Epinephrine Nasal Solution,beginning with “Rinse the stopper and mouth of the separator,”but use 10.0mLinstead of 5.0mLof chloroform in the determination of the specific rotation.Dry the empty aerosol container and valve,weigh them,and determine the net weight of the Inhalation Aerosol.Calculate the quantity,in mg,of C9H13NO3in the Inhalation Aerosol taken by the formula:
(183.20/309.32)(W)(0.5+0.5R/93),
in which 183.20and 309.32are the molecular weights of epinephrine and triacetylepinephrine,respectively,and Wis the weight,in mg,and Ris the specific rotation (in degrees,without regard to the sign),of the isolated triacetylepinephrine.
Auxiliary Information— Staff Liaison:Kahkashan Zaidi,Ph.D.,Senior Scientific Associate
Expert Committee:(AER)Aerosols
USP28–NF23Page 739
Phone Number:1-301-816-8269