Ethylcellulose
Cellulose, ethyl ether;
Cellulose ethyl ether
[9004-57-3].
(eth'' il sel' ue lose).
Cellulose, ethyl ether;
Cellulose ethyl ether
[9004-57-3].DEFINITION
Ethylcellulose is a partly O-ethylated cellulose. It contains NLT 44.0% and NMT 51.0% of ethoxy (–OC2H5) groups, calculated on the dried basis.
IDENTIFICATION
ASSAY
• Procedure
[Note—Hydriodic acid and its reaction byproducts are highly toxic. Perform all steps of the Sample solution preparation and the Standard solution preparation in a properly functioning hood. ]
Internal standard solution:
Dilute 120 µL of toluene with o-xylene to 10 mL.
Standard solution:
Transfer 100.0 mg of adipic acid, 4.0 mL of the Internal standard solution, and 4.0 mL of hydriodic acid into a suitable 10-mL thick-walled reaction vial with a pressure-tight septum closure. Close the vial tightly, and weigh the vial and contents accurately. Afterwards inject 50 µL of iodoethane through the septum with a syringe, weigh the vial again, and calculate the mass of iodoethane added, by difference. Shake well, and allow the layers to separate. Use the upper layer for analysis.
Sample solution:
Transfer 50.0 mg of Ethylcellulose, 50 mg of adipic acid, and 2.0 mL of the Internal standard solution into a suitable 5-mL thick-walled reaction vial with a pressure-tight septum closure. Cautiously add 2.0 mL of hydriodic acid, immediately close the vial tightly, and weigh the contents and the vial accurately. Shake the vial for 30 s, heat to 125
for 10 min, allow to cool for 2 min, shake again for 30 s, and heat to 125 for 10 min. Afterwards allow to cool for 2 min, and repeat shaking and heating for a third time. Allow the vial to cool for 45 min, and reweigh. If the loss is greater than 10 mg, discard the mixture and prepare another. Use the upper layer for analysis.
for 10 min, allow to cool for 2 min, shake again for 30 s, and heat to 125 for 10 min. Afterwards allow to cool for 2 min, and repeat shaking and heating for a third time. Allow the vial to cool for 45 min, and reweigh. If the loss is greater than 10 mg, discard the mixture and prepare another. Use the upper layer for analysis.
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
2-mm × 5.0-m stainless steel column packed with 3% G2 on 150–180-µm mesh support S1A
Temperature
Column:
80
Injector:
200
Detector:
200
Carrier gas:
Nitrogen
Flow rate:
15 mL/min
Injection volume:
1 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for iodoethane, toluene, and o-xylene are 0.6, 1.0, and 2.3, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between iodoethane and toluene
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ethoxy content of the Ethylcellulose as declared in the labeling:
Result = (451,000/312) × (RU × m2)/[(RS × m1) × (100 – d)]
| RU | = | = ratio of the iodoethane peak area to the toluene peak area from the Sample solution |
| m2 | = | = mass of iodoethane used in the Standard solution (mg) |
| RS | = | = ratio of the iodoethane peak area to the toluene peak area from the Standard solution |
| m1 | = | = mass of Ethylcellulose used in the Sample solution (mg) |
| d | = | = loss on drying as a percentage |
Acceptance criteria:
44.0%–51.0% on the dried basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 
281
:
NMT 0.5%, determined on 1.0 g
281:
NMT 0.5%, determined on 1.0 g
• Heavy Metals, Method II 231:
NMT 20 ppm
231:
NMT 20 ppm
• Chlorides
Solution A:
Nitric acid in water (1 in 5)
Standard stock solution:
0.824 mg/mL of sodium chloride
Standard solution:
8.24 µg/mL of sodium chloride, prepared from the Standard stock solution. [Note—Prepare immediately before use. ]
Sample solution:
Disperse 250 mg in 50 mL of water, heat to boiling, and allow to cool, shaking occasionally. Filter, and discard the first 10 mL of the filtrate.
Analysis
Samples:
Standard solution and Sample solution
Separately dilute 10 mL of the Sample solution and Standard solution with water to 15 mL, add 1 mL of Solution A, and pour the mixtures as a single addition into test tubes containing 1 mL of 0.1 N silver nitrate VS. Examine the tubes laterally against a black background.
Acceptance criteria:
After standing for 5 min protected from light, any opalescence in the Sample solution is not more intense than that in the Standard solution (0.1%).
Organic Impurities
• Procedure: Acetaldehyde
Solution A:
0.5 mg/mL of methylbenzothiazolone hydrazone hydrochloride
Solution B:
10 mg/mL of ferric chloride and 10 mg/mL of sulfamic acid
Standard stock solution:
10 mg/mL of acetaldehyde in 2-propanol. [Note—Use immediately. ]
[Note—Prepare the Standard solution and Sample solution at the same time. ]
Standard solution:
3 µg/mL of acetaldehyde from the Standard stock solution in water. [Note—Use immediately. ]
Sample solution:
Dissolve 3.0 g of ethylcellulose in 10 mL of water, stir by mechanical means for 1 h, allow to stand for 24 h, filter, and dilute the filtrate with water to 100.0 mL.
Analysis
Samples:
Standard solution and Sample solution
Transfer 5.0 mL of the Sample solution and Standard solution to separate flasks. To each flask add 5 mL of Solution A, and heat in a water bath at 60 for 5 min. Add 2 mL of Solution B, and heat again at 60 for 5 min. Cool, and dilute with water to 25.0 mL.
for 5 min. Add 2 mL of Solution B, and heat again at 60 for 5 min. Cool, and dilute with water to 25.0 mL.
Acceptance criteria:
The Sample solution is not more intensely colored than the Standard solution.
SPECIFIC TESTS
• Viscosity 911
911
Solution A:
Alcohol and toluene (1:4 w/w)
Sample solution:
Shake a quantity of Ethylcellulose, equivalent to 5.00 g of the dried substance, with 95 g of Solution A until the substance is dissolved.
Analysis:
Determine the viscosity using a capillary viscosimeter.
Acceptance criteria:
The viscosity (mPa·s) determined at 25 is NLT 80.0% and NMT 120.0% of that stated on the label for a nominal viscosity greater than 6 mPa·s; and NLT 75.0% and NMT 140.0% of that stated on the label for a nominal viscosity of NMT 6 mPa·s.
is NLT 80.0% and NMT 120.0% of that stated on the label for a nominal viscosity greater than 6 mPa·s; and NLT 75.0% and NMT 140.0% of that stated on the label for a nominal viscosity of NMT 6 mPa·s.
• Acidity or Alkalinity
Solution A:
Dissolve 100 mg of phenolphthalein in 80 mL of alcohol, and dilute with water to 100 mL.
Solution B:
Dilute 50 mg of methyl red with 1.86 mL of 0.1 N sodium hydroxide and 50 mL of alcohol, and dilute with water to 100 mL.
Sample solution:
To 0.5 g of Ethylcellulose add 25 mL of carbon dioxide-free water, and shake for 15 min. Pass through a sintered-glass filter with a maximum diameter of pores between 16 and 40 µm.
Analysis:
To 10 mL of Sample solution add 0.1 mL of Solution A and 0.5 mL of 0.01 N sodium hydroxide (Solution C). To 10 mL of Sample solution add 0.1 mL of Solution B and 0.5 mL of 0.01 N hydrochloric acid (Solution D).
Acceptance criteria:
Solution C is pink; Solution D is red.
• Loss on Drying 731:
Dry a sample at 105 for 2 h: it loses NMT 3.0% of its weight.
731:
Dry a sample at 105 for 2 h: it loses NMT 3.0% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
• Labeling:
Label it to indicate its nominal viscosity in mPa·s for a 5% m/m solution.
• USP Reference Standards 11
11
USP Ethylcellulose RS 
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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 1795
Pharmacopeial Forum: Volume No. 30(2) Page 706