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— USP Metaproterenol Sulfate RS.

Identification— The UV absorption 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 preparation prepared as directed in the Assay.

Delivered 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.

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 5 cm from the end of the oral inhalation actuator, perpendicular to the direction of the spray. Carefully rinse the slide with about 2 mL of 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 25 fields 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 5 µm along the longest axis. Record the number and size of all individual crystalline particles (not agglomerates) more than 10 µm in length measured along the longest axis: not more than 10 such 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 I under Water Determination 921, is not more than 0.075%.

Residual solvents 467: meets the requirements.

Assay— Cool an accurately weighed Inhalation Aerosol container for 10 minutes 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-mL separator with the aid of 30 mL of chloroform and 50 mL of 0.01 N hydrochloric acid. Reserve the valve and the empty container. Shake the separator for 1 minute and allow the phases to separate. Transfer the chloroform phase to a second 250-mL separator and the aqueous phase to a 250-mL volumetric flask. Wash the chloroform phase with two 50-mL portions of 0.01 N hydrochloric acid, add the washings to the 250-mL volumetric flask, dilute with 0.01 N hydrochloric acid to volume, and mix. Transfer an accurately measured volume of this stock solution, equivalent to about 10 mg of metaproterenol sulfate, to a 100-mL volumetric flask, dilute with 0.01 N hydrochloric acid to volume, and mix. Dissolve an accurately weighed quantity of USP Metaproterenol Sulfate RS in 0.01 N hydrochloric acid, and dilute quantitatively and stepwise with the same solvent to obtain a Standard solution having a known concentration of about 100 µg per mL. Concomitantly determine the absorbances of both solutions at the wavelength of maximum absorbance at about 276 nm, with a suitable spectrophotometer, using 0.01 N hydrochloric acid as the blank. Rinse the empty aerosol container and the valve with water and dry them at 105 for 10 minutes, 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 mL of the Inhalation Aerosol taken by the formula: in which C is the concentration, in µg per mL, of USP Metaproterenol Sulfate RS in the Standard solution, V is the volume, in mL, of stock solution taken, W is the weight, in g, of the Inhalation Aerosol taken, and AU and AS are 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-mL gas-tight syringe equipped with a linear valve. Calibrate the volume of the syringe by filling to the 5-mL mark with dichlorotetrafluoroethane withdrawn from a plastic-coated glass vial sealed with a neoprene multiple-dose rubber stopper and an aluminum seal, using 1.456 g per mL as the density of the calibrating liquid. Maintain the dichlorotetrafluoroethane, the Inhalation Aerosol sample, and the syringe (protected from becoming wet) at 25 in 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 w is the weight of the volume, v, of the Inhalation Aerosol taken.]

Expert Committee : (AER05) Aerosols05

USP29–NF24 Page 1361

Phone Number : 1-301-816-8269