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 á11ñ— USP Metaproterenol Sulfate RS.

Identification— The UVabsorption spectrum of the solution from the Assay preparation,obtained as directed in the Assay,exhibits maxima and minima at the same wavelengths as that of the Standard preparationprepared as directed in the Assay.

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.

Particle size— Prime the valve of an Inhalation Aerosol container by alternately shaking and firing it several times,and then actuate one measured spray onto a clean,dry microscope slide held 5cm from the end of the oral inhalation actuator,perpendicular to the direction of the spray.Carefully rinse the slide with about 2mLof chloroform,and allow to dry.Examine the slide under a microscope equipped with a calibrated ocular micrometer,using 450×magnification.Focus on the particles of 25fields of view near the center of the test specimen pattern,and note the size of the great majority of individual particles:they are less than 5µm along the longest axis.Record the number and size of all individual crystalline particles (not agglomerates)more than 10µm in length measured along the longest axis:not more than 10such particles are observed.

Water— Transfer the contents of a weighed container to the titration vessel by attaching the valve stem to an inlet tube.Weigh the empty container and determine the weight of the specimen taken.The water content,determined by Method Iunder Water Determination á921ñ,is not more than 0.075%.

Assay— Cool an accurately weighed Inhalation Aerosol container for 10minutes in a bath consisting of a mixture of acetone and solid carbon dioxide.Cut the valve from the aerosol container and allow the container to warm to room temperature.When most of the propellants have evaporated,transfer the residue in the container to a 250-mLseparator with the aid of 30mLof chloroform and 50mLof 0.01Nhydrochloric acid.Reserve the valve and the empty container.Shake the separator for 1minute and allow the phases to separate.Transfer the chloroform phase to a second 250-mLseparator and the aqueous phase to a 250-mLvolumetric flask.Wash the chloroform phase with two 50-mLportions of 0.01Nhydrochloric acid,add the washings to the 250-mLvolumetric flask,dilute with 0.01Nhydrochloric acid to volume,and mix.Transfer an accurately measured volume of this stock solution,equivalent to about 10mg of metaproterenol sulfate,to a 100-mLvolumetric flask,dilute with 0.01Nhydrochloric acid to volume,and mix.Dissolve an accurately weighed quantity of USP Metaproterenol Sulfate RSin 0.01Nhydrochloric acid,and dilute quantitatively and stepwise with the same solvent to obtain a Standard solution having a known concentration of about 100µg per mL.Concomitantly determine the absorbances of both solutions at the wavelength of maximum absorbance at about 276nm,with a suitable spectrophotometer,using 0.01Nhydrochloric acid as the blank.Rinse the empty aerosol container and the valve with water and dry them at 105for 10minutes,allow to cool,and weigh.Subtract the weight thus obtained from the original weight of the Inhalation Aerosol container to obtain the weight of the Inhalation Aerosol taken.Calculate the quantity,in mg,of metaproterenol sulfate [(C11H17NO3)2·H2SO4]in each mLof the Inhalation Aerosol taken by the formula: in which Cis the concentration,in µg per mL,of USP Metaproterenol Sulfate RSin the Standard solution,Vis the volume,in mL,of stock solution taken,Wis the weight,in g,of the Inhalation Aerosol taken,and AUand ASare the absorbances of the solution from the Inhalation Aerosol and the Standard solution,respectively.[The density,d,is determined as follows:Weigh a known volume (v)of the Inhalation Aerosol in a suitable 5-mLgas-tight syringe equipped with a linear valve.Calibrate the volume of the syringe by filling to the 5-mLmark with dichlorotetrafluoroethane withdrawn from a plastic-coated glass vial sealed with a neoprene multiple-dose rubber stopper and an aluminum seal,using 1.456g per mLas the density of the calibrating liquid.Maintain the dichlorotetrafluoroethane,the Inhalation Aerosol sample,and the syringe (protected from becoming wet)at 25in a water bath.Obtain the sample,equivalent to the same volume as that obtained during the sampling procedure,from the Inhalation Aerosol by means of a sampling device consisting of a replaceable rubber septum engaged in the plate threads at one end of a threaded fitting,the opposite end of which contains a sharpened tube capable of puncturing the aerosol container,and a rubber gasket around the tube to prevent leakage of the container contents after puncture.*Calculate the density taken by the formula: in which wis the weight of the volume,v,of the Inhalation Aerosol taken.]

Expert Committee:(AER)Aerosols

USP28–NF23Page 1227

Phone Number:1-301-816-8269