Polyethylene Oxide
»Polyethylene Oxide is a nonionic homopolymer of ethylene oxide,represented by the formula:
(OCH2CH2)n,
in which nrepresents the average number of oxyethylene groups.It is a white to off-white powder obtainable in several grades,varying in viscosity profile in an aqueous isopropyl alcohol solution.It may contain a suitable antioxidant.
Packaging and storage—
Preserve in tight,light-resistant containers.
Labeling—
The labeling indicates its viscosity profile in aqueous isopropyl alcohol solution.Label it to indicate the name and quantity of any added antioxidant.
Identification—
Test specimen:
previously dried in vacuum at room temperature to constant weight.
B:
The aqueous isopropyl alcohol solution viscosity,determined at 25
and in a concentration as directed in the labeling,falls within the viscosity range indicated by the labeling.
and in a concentration as directed in the labeling,falls within the viscosity range indicated by the labeling.
Loss on drying á731ñ—
Dry about 4g of it at 105for 45minutes:it loses not more than 1.0%of its weight.
for 45minutes:it loses not more than 1.0%of its weight.
Silicon dioxide and nonsilicon dioxide residue on ignition—
Weigh accurately about 1g into a previously ignited,tared 50-mLplatinum crucible.Add 4drops of sulfuric acid.Heat carefully on a hot plate until the specimen is thoroughly charred and fumes no longer are evolved.Ignite the crucible at 700±25(see Residue on Ignition á281ñ)to constant weight.Wet the residue carefully with 1mLof water,and slowly add 20drops of hydrofluoric acid.[Caution—Hydrofluoric acid is an extremely hazardous chemical.When handling it wear a face shield,arm protection,and rubber gloves,and perform the operation in a hood.
]Evaporate slowly on a hot plate to dryness,then ignite at 700±25for 10minutes,cool to room temperature in a desiccator,and weigh accurately.Repeat the addition of hydrofluoric acid,evaporation,and ignition,to constant weight.Calculate the percentage of silicon dioxide from the difference between the net weights before and after the hydrofluoric acid treatment:it is not more than 3.0%.Calculate the percentage of nonsilicon dioxide residue on ignition from the final net weight:it is not more than 2.0%.
(see Residue on Ignition á281ñ)to constant weight.Wet the residue carefully with 1mLof water,and slowly add 20drops of hydrofluoric acid.[Caution—Hydrofluoric acid is an extremely hazardous chemical.When handling it wear a face shield,arm protection,and rubber gloves,and perform the operation in a hood.
]Evaporate slowly on a hot plate to dryness,then ignite at 700±25for 10minutes,cool to room temperature in a desiccator,and weigh accurately.Repeat the addition of hydrofluoric acid,evaporation,and ignition,to constant weight.Calculate the percentage of silicon dioxide from the difference between the net weights before and after the hydrofluoric acid treatment:it is not more than 3.0%.Calculate the percentage of nonsilicon dioxide residue on ignition from the final net weight:it is not more than 2.0%.
Heavy metals,Method IIá231ñ:
0.001%.
Limit of free ethylene oxide—
Standard stock solution—
[Caution—Ethylene oxide is toxic and flammable.Prepare solutions of it in a well-ventilated fume hood.
]Using the special handling described in the following,complete the preparation.Ethylene oxide is a gas at room temperature.It is usually stored in a lecture-type gas cylinder or small metal pressure bomb.Chill the cylinder in a refrigerator before use.Transfer about 5mLof the liquid ethylene oxide to a cold,10-mLserum vial.Seal the vial,and store in a refrigerator.Transfer about 40g of acetone,accurately weighed,to a tared 50-mLserum vial that is capable of being tightly sealed with a polytef-lined septum and a metallic crimp cap.Seal the vial,and accurately weigh it.Using a gas-tight gas chromatographic syringe that has been chilled in a refrigerator,transfer about 60µLof the liquefied ethylene oxide to the same vial.Weigh the vial,and determine the amount added by weight difference.This Standard stock solutioncontains about 1µg of ethylene oxide per µL.[NOTE—This solution may be kept for 1week in the crimp-sealed serum vial,stored in a freezer.]
Standard preparations—
To four separate,tared 50-mLserum vials that are capable of being tightly sealed with polytef-lined septa and metallic crimp caps,transfer 1.0g of the Polyethylene Oxide under test.Seal the vials.To the separate vials,transfer 2.0,4.0,6.0,and 8.0µLof the Standard stock solution,and mix.These vials contain about 2,4,6,and 8µg of ethylene oxide,respectively,from the Standard stock solution.Heat the vials at 100for 30minutes,and cool to room temperature.
for 30minutes,and cool to room temperature.
Test preparation—
Transfer about 1g of the Polyethylene Oxide under test,accurately weighed,to a tared 50-mLserum vial that is capable of being tightly sealed with a polytef-lined septum and a metallic crimp cap.Weigh the vial,and determine the amount of Polyethylene Oxide added by weight difference.Seal the vial,heat at 100for 30minutes,and cool to room temperature.
for 30minutes,and cool to room temperature.
Chromatographic system
(see Chromatography á621ñ)—The gas chromatograph is equipped with a flame-ionization detector,a 0.53-mm ×10-m capillary column bonded with a 20-µm layer of phase G45,and a split injection system.The carrier gas is helium flowing at the rate of about 15mLper minute.The makeup gas is also helium with a split flow rate of about 15mLper minute.The injection port and detector temperatures are maintained at about 200and 250,respectively.The column temperature is maintained at about 70for 5minutes after injection,then programmed to increase at a rate of 10per minute to about 200and to maintain this temperature for 5minutes.Inject 300µLof the gaseous headspace from the vial of Standard preparationthat contains about 6µg of ethylene oxide from the Standard stock solutioninto the gas chromatograph,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 5%.
and 250,respectively.The column temperature is maintained at about 70for 5minutes after injection,then programmed to increase at a rate of 10per minute to about 200and to maintain this temperature for 5minutes.Inject 300µLof the gaseous headspace from the vial of Standard preparationthat contains about 6µg of ethylene oxide from the Standard stock solutioninto the gas chromatograph,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 5%.
Procedure—
[NOTE—Aheadspace apparatus that automatically transfers the measured amount of gaseous headspace may be used to perform the injections.]Using a gas-tight syringe,separately inject equal volumes (about 300µL)of the gaseous headspace of each of the Standard preparationsand the Test preparationinto the gas chromatograph,record the chromatograms,and measure the areas of the peak responses.Determine,based on a retention time comparison,whether ethylene oxide is detected in the Test preparation.Plot the responses of the Standard preparationsversus the content,in µg,of ethylene oxide in each vial,as furnished by the Standard stock solution,draw the straight line best fitting the four points,and calculate the correlation coefficient for the line.Asuitable system is one that yields a line having a correlation coefficient of not less than 0.99.Extrapolate the line until it intercepts the content axis on the negative side.From the intercept,determine the total amount,TU,in µg,of ethylene oxide in the Test preparation.Calculate the percentage of ethylene oxide in the portion of Polyethylene Oxide taken by the formula:
100(TU/W),
in which Wis the weight,in µg,of Polyethylene Oxide taken to prepare the Test preparation:the limit is 0.001%.
Organic volatile impurities,Method Iá467ñ:
meets the requirements.
Standard solution
and Test preparation—Prepare a Test preparationhaving a concentration of 20mg per mL,and prepare a Standard solutionhaving twice the stated concentration.
Auxiliary Information—
Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3057
Phone Number:1-301-816-8379