Ethylcellulose

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Portions of the monograph text that are national USP text, and are not part of the harmonized text, are marked with symbols to specify this fact.

Cellulose, ethyl ether,

Cellulose ethyl ether

CAS RN^®: 9004-57-3.

1 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.

It may contain a suitable antioxidant.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197F _{▲(CN 1-MAY-2020)}

Sample: Dissolve 40 mg in 1 mL of methylene chloride, spread 2 drops of this solution between two sodium chloride plates, then remove one of the plates to evaporate the solvent.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

[CAUTION-Hydriodic acid and its reaction byproducts are highly toxic. Perform all steps of the Standard solution and the Sample solution in a properly functioning hood. Specific safety practices to be followed are to be identified to the analyst performing this test.]

[NOTE-Prepare the solutions immediately before use.]

Internal standard solution: To 10 mL of o-xylene add 0.5 mL of n-octane and dilute to 100.0 mL with o-xylene.

Sample solution: To 30.0 mg of the substance to be examined, previously dried, add 60 mg of adipic acid in a 5-mL pressure-tight reaction vial equipped with a pressure-tight membrane stopper coated with polytetrafluoroethylene and secured with an aluminum crimped cap or any other sealing system providing a sufficient air-tightness. Add 2.00 mL of Internal standard solution and 1.0 mL of hydriodic acid and close immediately. Accurately weigh the vial (total mass before heating). Do not mix the contents of the vial by hand before heating. Place the vial in an oven or heat in a suitable heater, with continuous mechanical agitation, maintaining the internal temperature of the vial at 115 ± 2° for 70 min. Allow to cool and weigh accurately the vial (total mass after heating). If the difference of the total mass before heating to the total mass after heating is more than 10 mg, prepare a new test solution. After phase separation, pierce through the septum of the vial with a cooled syringe and withdraw a sufficient volume of the upper phase as the test solution.

Standard solution: Place 60 mg of adipic acid and 2.00 mL of Internal standard solution in another 5-mL reaction vial, add 1.0 mL of hydriodic acid and close immediately. Accurately weigh the vial, then inject 25 µL of jodoethane through the septum in the vial. Weigh again accurately and mix. After phase separation, pierce through the septum of the vial with a cooled syringe and withdraw a sufficient volume of the upper phase as the Standard solution.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53 - mm x 30 - m fused silica coated with 3-µm layer of phase G1. [NOTE-Use a guard column, if necessary.]

3.1.2 Temperatures

Injection port: 250°

Detector: 280°

Column: See Table 1.

Table 1

Flow rate: 4.2 mL/min

Carrier gas: Helium

Split ratio: 40:1

Injection volume: 1 µL

3.1.3 System suitability

Sample: Standard solution

[NOTE-The relative retention time is about 0.6 for iodoethane with reference to n-octane (retention time about 10 min).]

3.1.4 Suitability requirements

Resolution: NLT 5.0 between n-octane and iodoethane

Relative standard deviation: NMT 2.0%, using the response factor of the principal peak for six injections of the Standard solution

3.1.5 Analysis

Sample: Sample solution

[NOTE-Measure all of the peak areas, excluding the solvent peak.]

Calculate the response factor (F):

                      Result = (A₁ x W₁ x C)/( A₂ x 100)

A₁ = peak area of the internal standard peak from the Standard solution

W₁ = weight of iodoethane in the Standard solution (mg) 1

C = content of iodoethane from the certificate of the manufacturer (%)

A₂ = peak area of the iodoethane peak from the Standard solution

Calculate the percentage content (m/m) of the ethoxy group:

                      Result = (A₄ x F x M₁ x100)/(A₃ x W₂ x M₂)

A₄ = peak area of iodoethane from the Sample solution

F = response factor calculated from above

M₁ = molar mass of ethoxy group, 45.1

A₃ = peak area of the internal standard from the Sample solution 3

W₂ = weight of the sample (dried substance) in the Sample solution (mg)

M₂ = molar mass of iodoethane, 156.0

Acceptance criteria: NLT 44.0% and NMT 51.0% of ethoxy groups on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

Sample: 1.0 g

Acceptance criteria: NMT 0.5%

4.2 CHLORIDES

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 diluted nitric acid (125 g/L), 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%).

4.3 ACETALDEHYDE

Solution A: 0.5 mg/mL of methylbenzothiazolone hydrazone hydrochloride

Solution B: 10 mg/mL of ferric chloride and 16 mg/mL of sulfamic acid

Standard stock solution: 10 mg/mL of acetaldehyde in water. [NOTE-Use immediately. 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..

Acceptance criteria: The Sample solution is not more intensely colored than the Standard solution.

5 SPECIFIC TESTS

5.1 VISCOSITY-CAPILLARY METHODS (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 viscometer.

Acceptance criteria: The viscosity (mPas) determined at 25° is NLT 80.0% and NMT 120.0% of that stated on the label for a nominal viscosity greater than 6 mPas; and NLT 75.0% and NMT 140.0% of that stated on the label for a nominal viscosity of NMT 6 mPa-s.

5.2 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.

5.3 LOSS ON DRYING (731)

Sample: 1 g

Analysis: Dry at 105° for 2 h.

Acceptance criteria: It loses NMT 3.0% of its weight.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

LABELING: Label to indicate its nominal viscosity in mPas for a 5% m/m solution. The label states the name and amount of any added antioxidant.

USP REFERENCE STANDARDS (11)

USP Ethylcellulose RS,