Carbomer Copolymer

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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1 DEFINITION

Carbomer Copolymer is a high molecular weight copolymer of Acrylic acid and a long-chain alkyl methacrylate cross-linked with allyl ethers of pentaerythritol. Carbomer Copolymer contains NLT 52.0% and NMT 62.0% of carboxylic acid (-COOH) groups, calculated on the dried basis.

[NOTE-The heading of this monograph does not constitute the official title for a Carbomer Copolymer manufactured with the use of benzene. When benzene is used in the manufacturing process, the name will be Carbomer 1342, provided it complies with the existing requirements in the Carbomer 1342 monograph.]

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A. The IR absorption spectrum exhibits maxima only at the same wavelengths as those of a similar preparation of USP Carbomer Copolymer RS, treated in the same manner. [Note-If peak shifting occurs during testing using the method found in 197A causing the test to fail, follow the method found in 197K.]

B.

Sample: 5 g

Analysis: Add the Sample to 500 mL of water, and stir.

Acceptance criteria: A dispersion is formed, with a foam layer that persists after the dispersion is allowed to stand at room temperature for 1 h.

3 ASSAY

3.1 CARBOXYLIC ACID CONTENT

Sample: 400 mg, previously dried under vacuum at 80° for 1 h

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Electrode: Calomel-glass or silver/silver chloride

Titrant: 0.25 N sodium hydroxide VS

Endpoint detection: Potentiometric

Analysis: Slowly add the Sample to 400 mL of water in an 800–1000-mL beaker, while stirring continually at 1000 rpm. The stirrer shaft is set at an angle of about 60° and to one side of the beaker, and the propeller is positioned near the bottom. Continue stirring for 15 min. Allow the polymer dispersion to stand 30 min. Transfer to a magnetic stirring device, add a 7.62-cm stirring bar, mix moderately, add 1 g potassium chloride, and titrate.

Calculate the carboxylic acid content as a percentage of carboxylic acid groups in the portion of Carbomer Copolymer taken:

Result = [(V × N_A/W) × F] × 100

V = titrant volume (mL)

N = actual normality (mEq/mL)

W = sample weight (mg)

F = equivalency factor 45.02 mg/mEq

Acceptance criteria: 52.0%-62.0%

4 IMPURITIES

Change to read:

4.1 LIMIT OF ETHYL ACETATE AND CYCLOHEXANE

[Note-Required only for Carbomer Copolymers whose labeling indicates ethyl acetate or ethyl acetate/cyclohexane were used.]

Diluent: 166 mL/L of Dimethyl sulfoxide in water

Standard stock solution: 7 mg/g of cyclohexane and ethyl acetate in dimethyl sulfoxide

Standard solution A: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Weigh the vial. Using a syringe, add 10 µL of the Standard stock solution to the vial. Weigh the vial. Calculate the weight of the added Standard stock solution. Seal the vial with a Teflon-lined butyl rubber septum and aluminum crimp cap. Shake the vial for 1 h.

Standard solution B: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Weigh the vial. Using a syringe, add 20 µL of the Standard stock solution to the vial. Weigh the vial. Calculate the weight of the added Standard stock solution. Seal the vial with a Teflon-lined butyl rubber septum and aluminum crimp cap. Shake the vial for 1 h.

Standard solution C: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Weigh the vial. Using a syringe, add 50 µL of the Standard stock solution to the vial. Weigh the vial. Calculate the weight of the added Standard stock solution. Seal the vial with a Teflon-lined butyl rubber septum and aluminum crimp cap. Shake the vial for 1 h.

Sample solution: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Seal the vial with a Teflon-lined septum and aluminum crimp cap. Shake for 1 h.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC, equipped with a headspace injector

Detector: Flame ionization

Column: 0.53 - mm * 30 - m fused silica; coated with 3.0-µm stationary phase G43

Temperatures

Injection port: 140°

Detector:

250°

Column: See Table 1.

Carrier gas: Helium

Flow rate: 5 mL/min (at a linear velocity of 35 cm/s programmed in constant pressure mode)

Injection volume: 1 mL (gaseous phase)

Injection type: Split, split ratio, 5:1

[NOTE-The following headspace conditions may be used: a vial pressure of 10 psi, a loop fill pressure (if equipped) of 7 psi, and a transfer line temperature of 105°.]

Vial temperature: The vials are maintained at a temperature of 80° for 45 min before headspace injection.

System suitability

Sample: Standard solution B

Suitability requirements

Relative standard deviation: NMT 15% from 3 injections

Analysis

Samples: (ERR 1-Jun-2021) Standard solution A, Standard solution B, Standard solution C, and Sample solution

The detector response factor (RF) of each Standard solution is determined by:

RF = (W_SS × C_SS)/(r_S - r_U)

W_SS = weight of the Standard stock solution added into each Standard solution (g)

C_SS = concentration of ethyl acetate or cyclohexane in Standard stock solution (mg/g) Css

r_S = peak area of ethyl acetate or cyclohexane in each Standard solution

r_U = peak area of ethyl acetate or cyclohexane in the Sample solution

Average three RF to obtain RF avg. Calculate the percentage of ethyl acetate or cyclohexane in the portion of Carbomer Copolymer taken:

Result = [(RF_avg× r_U)/W_U] × 100

RF_avg = average of three RF avg

r_U = peak area of ethyl acetate or cyclohexane in the Sample solution

W_U = weight of Carbomer Copolymer added into the Sample solution (mg)

Acceptance criteria

Ethyl acetate: NMT 0.5%

Cyclohexane: NMT 0.3%

Change to read:

4.2 LIMIT OF BENZENE

Diluent: 166 mL/L of dimethyl sulfoxide in water

Standard stock solution: 1.2 µg/g of benzene in dimethyl sulfoxide

Standard solution A: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Weigh the vial. Using a syringe, add 10 µL of the Standard stock solution to the vial. Weigh the vial. Calculate the weight of the added Standard stock solution. Seal the vial with a Teflon-lined butyl rubber septum and aluminum crimp cap. Shake the vial for 1 h.

Standard solution B: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Weigh the vial. Using a syringe, add 50 µL of the Standard stock solution to the vial. Weigh the vial. Calculate the weight of the added Standard stock solution. Seal the vial with a Teflon-lined butyl rubber septum and aluminum crimp cap. Shake the vial for 1 h.

Standard solution C: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Weigh the vial. Using a syringe, add 100 µL of the Standard stock solution to the vial. Weigh the vial. Calculate the weight of the added Standard stock solution. Seal the vial with a Teflon-lined butyl rubber septum and aluminum crimp cap. Shake the vial for 1 h.

Sample solution: Transfer 50 ± 1 mg of Carbomer Copolymer to a 20-mL headspace vial, and add 6 mL of Diluent to the vial. Seal the vial with a Teflon-lined septum and aluminum crimp cap. Shake for 1 h.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC, equipped with a headspace injector

Detector: Flame ionization

Column: 0.53 - mm * 30 - m fused silica; coated with 3.0-µm stationary phase G46

Temperatures

Injection port: 140°

Detector: 250°

Column: See Table 2.

Table 2

Carrier gas: Helium

Flow rate: 5 mL/min (at a linear velocity of 35 cm/s programmed in constant pressure mode)

Injection volume: 1 mL (gaseous phase)

Injection type: Split, split ratio, 0.5: 1

[NOTE-The following headspace conditions may be used: a vial pressure of 10 psi, a loop fill pressure (if equipped) of 7 psi, and a transfer

line temperature of 105°.]

Vial temperature: The vials are maintained at a temperature of 80° for 45 min before headspace injection.

System suitability

Sample: Standard solution B

Suitability requirements

Relative standard deviation: NMT 15% from 3 injection

Analysis

Samples: (ERR 1-Jun-2021) Standard solution A, Standard solution B, Standard solution C, and Sample solution

The detector response factor (RF) of each Standard solution is determined by:

RF= (W_SS × C_SS)/(r_S - r_U)

W_SS = weight of the Standard stock solution in each Standard solution (g)

C_SS = concentration of benzene in the Standard stock solution (µg/g) CSS

r_S = peak area of benzene in each Standard solution

r_U = peak area of benzene in the Sample solution

Average three RF to obtain RF Calculate the percentage of benzene in the portion of Carbomer Copolymer taken: avg

Result = [(RF_avg× r_U)/W_U] × 100

RF_avg = average of three RF avg

r_U = peak area of benzene in the Sample solution

W_U = weight of Carbomer Copolymer in the Sample solution (µg)

Acceptance criteria: NMT 0.0002%, corresponding toNMT 2 µg/g

Acceptance criteria: NMT 0.0002%, corresponding toNMT 2 µg/g

4.3 LIMIT OF ACRYLIC ACID

Solution A: Methanol

Solution B: Dissolve 6.80 g of monobasic potassium phosphate in 300 mL of water, dilute with water to 500 mL. Dilute 100 mL of this solution with water to 1 L, adjust with phosphoric acid to a pH of 3.0 ± 0.1. Filter and degas.

Mobile phase: See Table 3.

Table 3

Standard solution A: 2 µg/g of acrylic acid (w/w)

Standard solution B: 50 µg/g of acrylic acid (w/w)

Standard solution C: 100 µg/g of acrylic acid (w/w)

Sample solution: Transfer 100 mg of Carbomer Copolymer to a tared serum vial. Add water to obtain a total weight of 10 g of solution. Cap the vial, and shake by mechanical means for 2 h. Add 2 drops of sodium hydroxide solution (50% w/v), and shake by hand for 15 s. Add 1.0 mL of calcium chloride solution (100 mg/mL), and shake until the gel collapses. Record the weight of all additions of water, sodium hydroxide, and calcium chloride. Centrifuge for 15 min, and use the clear supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 4.6-mm × 15-cm; 5 µm packing L1

Flow rate: See Table 3.

Injection volume: 10 µL

System suitability

Sample: Standard solution B

Suitability requirements

Relative standard deviation: NMT 5% from 3 injections

Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, and Sample solution

Analyze each Standard solution, and plot the peak area versus concentration. Plot should be linear with an r² equal or greater than 0.9990. The slope of the calibration curve (area/ppm acrylic acid) is the response factor. Calculate the percentage of free acrylic acid in the portion of Carbomer Copolymer taken:

Result (wt%) = (r_U/RF)/C_U × F × 100

r_U = peak response of acrylic acid from the Sample solution

RF = response factor [peak area/(µg/g)]

C_U = concentration of Carbomer Copolymer in the Sample solution (mg/g) Cu

F = unit conversion factor, 10-3 (mg/µg)

Acceptance criteria: NMT 0.25%

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731)

Analysis: Dry under vacuum at 80° for 1 h.

Acceptance criteria: NMT 2.0%

5.2 VISCOSITY-ROTATIONAL METHODS (912)

Sample: 5.00 g of Carbomer Copolymer, previously dried under vacuum at 80° for 1 h

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Electrode: Calomel-glass or silver/silver chloride

Titrant: 180 mg/mL of sodium hydroxide

Endpoint detection: PH

Analysis: Carefully add the Sample to 500 mL of water in an 800-mL beaker, while stirring continuously at 1000 ± 10 rpm, with the stirrer shaft set to one side of the beaker at an angle of 60° and the propeller positioned near the bottom of the beaker. Allow 45-90 s for addition of the Sample at a uniform rate, being sure that loose aggregates of powder are broken up, and continue stirring at 1000 ± 10 rpm for 15 min. [NOTE-Proper dispersion of the carbomer resin is imperative for accurate viscosity readings.] Remove the stirrer, and place the beaker containing the dispersion in a 25 ± 0.1° water bath for 30 min. Insert a paddle stirrer to a depth necessary to ensure that air is not drawn into the dispersion; and while stirring at 300 ± 25 rpm, titrate with Titrant to a pH of 7.3-7.8. Stir 2-3 min until neutralization is complete. [NOTE-After neutralization, care must be taken to avoid excessively high shearing, because aggressive mixing will break the polymer chains and reduce the viscosity reading.] Then determine the final pH. [NOTE-If the pH is below 7.3, raise it with additional Titrant. If it is above 7.8, discard the mucilage, and prepare another batch, using a smaller amount of Titrant for titration.]

Return the beaker containing the neutralized mucilage to the 25 ± 0.1° water bath for 1 h. Equip a suitable rotational viscometer 2 with a suitable spindle as defined in Table 4. The spindle rotates at 20 rpm. Follow the instrument manufacturer's directions to measure the apparent viscosity. Perform the viscosity determination without delay to avoid the slight viscosity changes that occur 75 min after neutralization.

Table 4

^a Cylinder diameter.

^b Cylinder height.

^c Shaft diameter.

^d Distance from the top of the cylinder to the lower tip of the shaft.

^e Spindle immersion depth.

Acceptance criteria: See Table 5.

Table 5

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Product is hygroscopic. Preserve in tight containers away from direct sources of moisture.

LABELING: If benzene has been used in the manufacturing process, the name of the article will be Carbomer 1342, provided it complies with and is labeled in accordance with the requirements set forth in that monograph. If benzene is not used in the manufacturing process, label it to indicate whether it is Type A, B, or C; and label it to state the measured viscosity, giving the viscosity measurement parameters, the concentration of the solution, and the type of equipment used; the solvent or solvents used in the polymerization process; and the nominal and residual solvent levels for each solvent.

USP REFERENCE STANDARDS (11)

USP Carbomer Copolymer RS

¹ A beaker size of 600-1000 mL is ideal for this method. However, the minimum inside diameter of the beaker should be 83 mm.

² Available as a Brookfield RV viscometer, or equivalent.