Polyoxyl 20 Cetostearyl Ether
(pol'' ee ox' il see'' toe steer' il ee' ther).
» Polyoxyl 20 Cetostearyl 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 17.2 and not more than 25.0 oxyethylene units.
Packaging and storage—
Preserve in tight containers, in a cool place.
USP Reference standards 
11
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11—
USP Polyoxyl 20 Cetostearyl Ether RS
Identification, Infrared Absorption 197F, on undried specimen.
197F, on undried specimen.
Acid value 401:
not more than 0.5.
401:
not more than 0.5.
Hydroxyl value 401:
between 42 and 60.
401:
between 42 and 60.
Saponification value 401:
not more than 2.
401:
not more than 2.
pH 791:
between 4.5 and 7.5, determined in a solution (1 in 10).
791:
between 4.5 and 7.5, determined in a solution (1 in 10).
Water, Method I 921:
not more than 1.0%.
921:
not more than 1.0%.
Residue on ignition—
Weigh accurately about 25 g into a tared 40-mL porcelain 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 ± 100
for 1 hour. 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%.
for 1 hour. 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%.
Heavy metals, Method II 231:
0.002%.
231:
0.002%.
Free ethylene oxide—
Internal standard solution—
Prepare a solution containing 100 mg of n-butyl chloride in each mL of 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 250 mL of chlorobenzene in a glass-stoppered, 500-mL conical flask. Bubble ethylene oxide through the chlorobenzene at a moderate rate for about 30 minutes, insert the stopper, and store protected from heat. Pipet 25 mL of 0.5 N alcoholic hydrochloric acid solution, prepared by mixing 45 mL of hydrochloric acid with 1 L of alcohol, into a 500-mL conical flask containing 40 g of magnesium chloride hexahydrate. Shake the mixture to effect saturation. Pipet 10 mL of the ethylene oxide solution into the flask, and add 20 drops of bromocresol green TS. If the solution is not yellow (acid) at this point, add an additional volume, accurately measured, of 0.5 N alcoholic hydrochloric acid to give an excess of about 10 mL. Record the total volume of 0.5 N alcoholic hydrochloric acid added. Insert the stopper in the flask, and allow to stand for 30 minutes. Titrate the excess acid with 0.5 N alcoholic potassium hydroxide VS. Perform a blank titration, using 10.0 mL of chlorobenzene instead of ethylene oxide solution, adding the same total volume of 0.5 N alcoholic hydrochloric acid, and note the difference in volumes required. Each mL of the difference in volumes of 0.5 N alcoholic potassium hydroxide consumed is equivalent to 22.02 mg of ethylene oxide. Calculate the concentration, in mg per mL, of ethylene oxide in the Standard solution. Standardize daily.
Standard preparation—
Transfer about 5 g of Polyoxyl 20 Cetostearyl Ether to a suitable glass bottle of about 60-mL capacity, and add 10 mL of chlorobenzene, exactly 50 µL of Internal standard solution, and an accurately measured volume of Standard solution containing about 0.5 mg of ethylene oxide. Insert a magnetic stirring bar, cap the bottle tightly, and stir until homogeneity is attained.
Test preparation—
Transfer about 5 g of Polyoxyl 20 Cetostearyl Ether, accurately weighed, to a suitable glass bottle of about 60-mL capacity, and add 10 mL of chlorobenzene and 50 µL, accurately measured, of Internal standard solution. Add a volume of chlorobenzene equal to the volume of the Standard solution added to prepare the Standard preparation. 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 3-mm (OD) × 1.8-m stainless steel column packed with S3. The injection port and detector block temperatures are maintained at about 210 and 230, respectively, and the column temperature is maintained at about 160. Helium is used as the carrier gas at a flow rate of 66 mL per minute.
and 230, respectively, and the column temperature is maintained at about 160. Helium is used as the carrier gas at a flow rate of 66 mL per 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 2 µL of the Standard preparation into a suitable gas chromatograph, and record the chromatogram. Similarly, inject about 2 µL of the Test preparation, and record the chromatogram. Calculate the weight, in g, of ethylene oxide in the Test preparation (WT) by the formula:
(WE WU RU)/1000(WU RS – WS RU)
in which WE is the weight, in mg, of ethylene oxide added to the Standard preparation; WU and WS are the weights, in g, of Polyoxyl 20 Cetostearyl Ether used to prepare the Test preparation and the Standard preparation, respectively; and RU and RS are the area ratios of ethylene oxide to internal standard in the chromatograms for the Test preparation and the Standard preparation, respectively. Calculate the percentage of ethylene oxide in the portion of Polyoxyl 20 Cetostearyl Ether taken by the formula:
100WT / WU
in which WT and WU are as defined previously. The limit is 0.01%.
Free polyethylene glycols—
Transfer about 12 g, accurately weighed, to a 500-mL separator containing 50 mL of ethyl acetate. Add 50 mL of sodium chloride solution (29 in 100), shake vigorously for 2 minutes, and allow to separate for 15 minutes. Drain the lower, aqueous phase into a second 500-mL separator, and extract the upper layer with a second 50-mL portion of sodium chloride solution (29 in 100). To the combined aqueous layers add 50 mL of ethyl acetate, shake vigorously for 2 minutes, and allow to separate as before. Drain the lower, aqueous phase into a third 500-mL separator, and extract with two 50-mL portions of chloroform, by shaking for 2 minutes each time. Evaporate the combined chloroform extracts in a 150-mL beaker on a steam bath, with the aid of a stream of nitrogen, to apparent dryness. Redissolve in about 15 mL of chloroform, and transfer to a filter, collecting the filtrate in a 150-mL beaker. 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 20 Cetostearyl Ether in a 50 water bath overnight, in order to melt it completely. Shake vigorously to eliminate any possibility of molecular weight gradients within it, and transfer 200 µL to a 5- × 180-mm high-resolution NMR sample tube. Add 200 µL of deuterated chloroform by means of a separate microsyringe. Add 5 drops of tetramethylsilane as an internal reference standard. Cap the tube tightly, and shake thoroughly. Place the tube in the NMR spectrometer, and record the NMR spectrum at an appropriate RF power level and a sweep time of 250 seconds per 500 Hz (see Qualitative scans under Nuclear Magnetic Resonance 761). Adjust the spectrum amplitude so that the signal at 1.1 ppm is at least 80% of full-scale. Record the integral areas from 0.4 ppm to 2.35 ppm (A1), and from 2.35 ppm to 4.9 ppm (A2) at a sweep time of 50 seconds per 500 Hz at an integral power level such that the integral of the ethylene oxide peak at 3.5 ppm 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:
water bath overnight, in order to melt it completely. Shake vigorously to eliminate any possibility of molecular weight gradients within it, and transfer 200 µL to a 5- × 180-mm high-resolution NMR sample tube. Add 200 µL of deuterated chloroform by means of a separate microsyringe. Add 5 drops of tetramethylsilane as an internal reference standard. Cap the tube tightly, and shake thoroughly. Place the tube in the NMR spectrometer, and record the NMR spectrum at an appropriate RF power level and a sweep time of 250 seconds per 500 Hz (see Qualitative scans under Nuclear Magnetic Resonance 761). Adjust the spectrum amplitude so that the signal at 1.1 ppm is at least 80% of full-scale. Record the integral areas from 0.4 ppm to 2.35 ppm (A1), and from 2.35 ppm to 4.9 ppm (A2) at a sweep time of 50 seconds per 500 Hz at an integral power level such that the integral of the ethylene oxide peak at 3.5 ppm 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 32 is the total number of protons in the molecule not activated by oxygen, averaged for the cetyl and stearyl radicals, 3 is the number of oxygen-activated protons not included in the oxyethylene unit count, 4 is the number of protons in each oxyethylene unit.
3) / 4
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Robert H. Lafaver, M.S.
Scientific Liaison 1-301-816-8335 |
(EXC2010) Monographs - Excipients |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 1915
Pharmacopeial Forum: Volume No. 31(3) Page 817