Polyoxyl 20Cetostearyl Ether
»Polyoxyl 20Cetostearyl Ether is a mixture of mono-cetostearyl (mixed hexadecyl and octadecyl)ethers of mixed polyoxyethylene diols,the average polymer length being equivalent to not less than 17.2and not more than 25.0oxyethylene units.
Packaging and storage— Preserve in tight containers,in a cool place.
Identification,Infrared Absorption á197Fñ,on undried specimen.
Acid value á401ñ: not more than 0.5.
Hydroxyl value á401ñ: between 42and 60.
Saponification value á401ñ: not more than 2.
pHá791ñ: between 4.5and 7.5,determined in a solution (1in 10).
Water,Method Iá921ñ: not more than 1.0%.
Residue on ignition— Weigh accurately about 25g into a tared 40-mLporcelain crucible,and heat in contact with air until it ignites spontaneously or can be ignited with a glowing splint.Allow the flame to go out,place the crucible in a muffle furnace with the door partly open until the carbon is consumed,close the door,and heat at 700±100for 1hour.Cool in a desiccator,weigh,and calculate the percentage of residue.If the amount so obtained exceeds 0.4%,again heat until constant weight is attained:the limit is 0.4%.
Free ethylene oxide—
Internal standard solution— Prepare a solution containing 100mg of n-butyl chloride in each mLof chlorobenzene.Store in a tightly closed container.Prepare fresh weekly.
Standard solution— [Caution—Ethylene oxide is toxic and flammable.Prepare this solution in a well-ventilated hood,using great care. ]Place 250mLof chlorobenzene in a glass-stoppered,500-mLconical flask.Bubble ethylene oxide through the chlorobenzene at a moderate rate for about 30minutes,insert the stopper,and store protected from heat.Pipet 25mLof 0.5Nalcoholic hydrochloric acid solution,prepared by mixing 45mLof hydrochloric acid with 1liter of alcohol,into a 500-mLconical flask containing 40g of magnesium chloride hexahydrate.Shake the mixture to effect saturation.Pipet 10mLof the ethylene oxide solution into the flask,and add 20drops of bromocresol green TS.If the solution is not yellow (acid)at this point,add an additional volume,accurately measured,of 0.5Nalcoholic hydrochloric acid to give an excess of about 10mL.Record the total volume of 0.5Nalcoholic hydrochloric acid added.Insert the stopper in the flask,and allow to stand for 30minutes.Titrate the excess acid with 0.5Nalcoholic potassium hydroxide VS.Perform a blank titration,using 10.0mLof chlorobenzene instead of ethylene oxide solution,adding the same total volume of 0.5Nalcoholic hydrochloric acid,and note the difference in volumes required.Each mLof the difference in volumes of 0.5Nalcoholic potassium hydroxide consumed is equivalent to 22.02mg of ethylene oxide.Calculate the concentration,in mg per mL,of ethylene oxide in the Standard solution.Standardize daily.
Standard preparation— Transfer about 5g of USP Polyoxyl 20Cetostearyl Ether RSto a suitable glass bottle of about 60-mLcapacity,and add 10mLof chlorobenzene,exactly 50µLof Internal standard solution,and an accurately measured volume of Standard solutioncontaining about 0.5mg of ethylene oxide.Insert a magnetic stirring bar,cap the bottle tightly,and stir until homogeneity is attained.
Test preparation— Transfer about 5g of Polyoxyl 20Cetostearyl Ether,accurately weighed,to a suitable glass bottle of about 60-mLcapacity,and add 10mLof chlorobenzene and 50µL,accurately measured,of Internal standard solution.Insert a magnetic stirring bar,cap the bottle tightly,and stir until homogeneity is attained.
Chromatographic system— Under typical conditions,the instrument is equipped with a flame-ionization detector,and contains a 1.8-m ×3-mm (OD)stainless steel column packed with S3.The injector port and detector block are maintained at about 210and 230,respectively,and the column at about 160.Helium is used as the carrier gas at a flow rate of 66mLper minute.
Interference check— Inject a suitable volume of chlorobenzene into the gas chromatograph,and allow the chromatogram to run until the solvent has eluted.Similarly inject and chromatograph the Internal standard solution,the Standard solution,and a solution prepared according to the directions for the Test preparation,but omitting the internal standard.No interfering peaks are observed.
Procedure— Inject about 2µLof the Standard preparationinto a suitable gas chromatograph,and record the chromatogram.Similarly,inject about 2µLof the Test preparation,and record the chromatogram.Calculate the quantity,in mg,of ethylene oxide in the portion of Polyoxyl 20Cetostearyl Ether taken by the formula:
WS(RU/RS),
in which WSis the weight,in mg,of ethylene oxide in the portion of Standard solutiontaken,and RUand RSare the area ratios of ethylene oxide to internal standard in the chromatograms for the Test preparationand the Standard preparation,respectively.The limit is 0.01%.
Free polyethylene glycols— Transfer about 12g,accurately weighed,to a 500-mLseparator containing 50mLof ethyl acetate.Add 50mLof sodium chloride solution (29in 100),shake vigorously for 2minutes,and allow to separate for 15minutes.Drain the lower,aqueous phase into a second 500-mLseparator,and extract the upper layer with a second 50-mLportion of sodium chloride solution (29in 100).To the combined aqueous layers add 50mLof ethyl acetate,shake vigorously for 2minutes,and allow to separate as before.Drain the lower,aqueous phase into a third 500-mLseparator,and extract with two 50-mLportions of chloroform,by shaking for 2minutes each time.Evaporate the combined chloroform extracts in a 150-mLbeaker on a steam bath,with the aid of a stream of nitrogen,to apparent dryness.Redissolve in about 15mLof chloroform,and transfer to a filter,collecting the filtrate in a 150-mLbeaker.Rinse the funnel with several small portions of chloroform,and evaporate the combined filtrate and rinsings,as described above,until no odor of chloroform or ethyl acetate is perceptible.Cool in a desiccator,and weigh:the limit is 7.5%.
Average polymer length— Place the Polyoxyl 20Cetostearyl Ether in a 50water bath overnight,in order to melt it completely.Shake vigorously to eliminate any possibility of molecular weight gradients within it,and transfer 200µLto a 5-×180-mm high-resolution NMRsample tube.Add 200µLof deuterated chloroform by means of a separate microsyringe.Add 5drops of tetramethylsilane as an internal reference standard.Cap the tube tightly,and shake thoroughly.Place the tube in the NMRspectrometer,and record the NMRspectrum at an appropriate RFpower level and a sweep time of 250seconds per 500Hz (see Qualitative scansunder Nuclear Magnetic Resonance á761ñ).Adjust the spectrum amplitude so that the signal at 1.1ppm is at least 80%of full-scale.Record the integral areas from 0.4ppm to 2.35ppm (A1),and from 2.35ppm to 4.9ppm (A2)at a sweep time of 50seconds per 500Hz at an integral power level such that the integral of the ethylene oxide peak at 3.5ppm is at least 80%of full chart height.Do not change the power level during the sweep.Record the integral of each peak several times,and calculate the average integral area.Calculate the number of oxyethylene units,n,per molecule taken by the formula:
n =(32A2/A1-3)/4,
in which 32is the total number of protons in the molecule not activated by oxygen,averaged for the cetyl and stearyl radicals,3is the number of oxygen-activated protons not included in the oxyethylene unit count,4is the number of protons in each oxyethylene unit.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3059
Phone Number:1-301-816-8379