Carbomer Homopolymer
(Title for this new monograph—to become official January 1, 2011)
(Prior to January 1, 2011, the current practice of labeling the article of commerce with the name Carbomer 934, Carbomer 934P, Carbomer 940, or Carbomer 941, whichever is appropriate, may be continued.)
Change to read:
» Carbomer Homopolymer is a high molecular weight polymer of acrylic acid cross-linked with allyl ethers of polyalcohols. Carbomer Homopolymer, previously dried, contains not less than 56.0 percent and not more than 68.0 percent of carboxylic acid (–COOH) groups.
[note—This monograph applies to, but is not limited to, Carbomer 934, Carbomer 934P, Carbomer 940, and Carbomer 941 manufactured without benzene.NF27 The heading of this monograph does not constitute the official title for a Carbomer Homopolymer manufactured with the use of benzene. When benzene is used in the manufacturing process, the name of the article will be Carbomer 934, Carbomer 934P, Carbomer 940, or Carbomer 941, whichever is appropriate. NF27]
Packaging and storage— Preserve in tight containers, at a temperature not exceeding 45.
Change to read:
Labeling— LabelNF27 it to indicate whether it is Type A, B, or C; and also to state the measured viscosity, giving the viscosity measurement parameters, the concentration of the solution, and the type of equipment used;NF27 the solvent or solvents used in the polymerization process; and the nominal and residual solvent levels for each solvent.
Identification—
A: Infrared Absorption 197K—The IR spectrum exhibits main bands at or near (±5) wave numbers (cm1) 1710, 1454, 1414, 1245, 1172, 1115, and 801, with the strongest band at 1710.
B: Adjust a 1 in 100 dispersion of it with 1 N sodium hydroxide to a pH of about 7.5: a viscous gel is produced.
C: Add 2 mL of a 1 in 10 aqueous solution of calcium chloride, while stirring, to 10 mL of the gel obtained from Identification test B: a white precipitate is immediately produced.
D: Prepare a 1 in 100 dispersion of it. Add 0.5 mL of thymol blue TS to 10 mL of the dispersion: an orange color is produced. To another 10 mL of the dispersion add 0.5 mL of cresol red TS: a yellow color is produced.
Change to read:
Viscosity 911— Carefully add 2.50 g of the resin, which has been previously dried, to 500 mL of water in a 800-mL beaker, while stirring continuously at 1000 ± 50 rpm. The stirrer shaft is set at an angle of 60 and positioned at one side of the beaker, and the propeller is positioned near the bottom of the beaker. The stirrer used should be a three-blade, 2-inch marine impeller. Add Carbomer Homopolymer at a uniform rate over a period of 45 to 60 seconds, being sure that loose aggregates of powder are broken up, and continue stirring at 1000 ± 50 rpm for 15 minutes. [note—Proper dispersion of the Carbomer Homopolymer resin is imperative for accurate viscosity readings.] Remove the stirrer, and allow the beaker containing the dispersion to stand at controlled room temperature for 30 minutes. Insert a paddle stirrer to a depth necessary to ensure that the air is not drawn into the dispersion, and while stirring at 300 ± 25 rpm, titrate potentiometrically (see Titrimetry 541) with sodium hydroxide solution (18 in 100) to a pH of between 7.3 and 7.8.NF27 After adding the sodium hydroxide solution, stir with a paddle mixer at 300 ± 25 rpm for 2 to 3 minutes. [note—After neutralization, care must be taken to avoid excessively high shearing, as aggressive mixing will break the polymer chains and reduce the viscosity reading.] Take the final pH reading with a pH meter to make sure it is between 7.3 and 7.8. [note—If the pH is below 7.3, raise the pH with additional sodium hydroxide. If the pH is above 7.8, discard the mucilage, and prepare another using a smaller amount of sodium hydroxide for titration.] Place the neutralized mucilage into a water bath maintained at 25 ± 0.1 for 1 hour. Measure the pH again, and make certain the mucilage pH is between 7.3 and 7.8. Perform the viscosity determination without delay to avoid slight viscosity changes occurring after 75 minutes of neutralization.NF27
Equip a suitable rotational viscometer1NF27 with a suitable spindle, as defined in the chart below. For spindle dimensions, consult the table under Carbomer Copolymer.
Expected
Viscosity
(mPa·s)NF27		 Spindle Number Multiplier
100–400 1 5
400–1600 2 20
1000–4000 3 50
2000–8000 4 100
4000–16,000 5 200
10,000–40,000 6 500
40,000–160,000 7 2000
The spindle rotates at 20 rpm. Follow the instrument manufacturer's directions to measure the apparent viscosity.NF27 The viscosity values, determined by the conditions specified herein, are within the limits specified in the accompanying table.
Carbomer Homopolymer Viscosity Specified (mPa·s)NF27
A 4,000–11,000
B 25,000–45,000
C 40,000–60,000
Loss on drying 731— Dry it in vacuum at 80 for 1 hour: it loses not more than 2.0% of its weight.
Change to read:
Residue on ignition 281:NF27 not more than 4.0%, determined on 1.0 g.
Heavy metals, Method II 231: not more than 0.002%.
Limit of ethyl acetate and cyclohexane— [note—This test is required only for those Carbomer Homopolymers whose labeling indicates that ethyl acetate or a mixture of ethyl acetate and cyclohexane was used in the polymerization process.]
Standard stock solution— Transfer 5.0 mL of methanol to a 10-mL serum vial, insert a rubber septum, and seal with a metal cap. Add an accurately weighed quantity of about 25.0 µL of ethyl acetate and 20.0 µL of cyclohexane through the septum into the vial, and mix.
Standard solution— Transfer 20.0 mL of methanol to a 30-mL serum vial, insert a rubber septum, and seal with a metal cap. Through the rubber septum, add 10 µL of methyl ethyl ketone (internal standard) and 50.0 µL of the Standard stock solution, and mix.
Test solution— Transfer about 50 mg of Carbomer Homopolymer, accurately weighed, to a 30-mL serum vial, add 20 mL of methanol, insert a rubber septum, and seal with a metal cap. Through the rubber septum, add 10 µL of methyl ethyl ketone, and mix.
Chromatographic system (see Chromatography 621)— Proceed as directed under Carbomer Copolymer.
Procedure— Proceed as directed under Carbomer Copolymer, except to calculate the percentages of ethyl acetate and cyclohexane in the portion of Carbomer Homopolymer taken by the formula:
100(WS / WT)(RU / RS)
in which WS is the weight, in mg, of ethyl acetate or cyclohexane, as appropriate, in the Standard solution; WT is the weight, in mg, of Carbomer Homopolymer taken to prepare the Test solution; and RU and RS are the peak area ratios of the relevant analyte peak to the methyl ethyl ketone peak obtained from the Test solution and the Standard solution, respectively: not more than 0.5% of ethyl acetate and not more than 0.3% of cyclohexane is found.
Change to read:
Limit of benzene— NF27
Solvent solution— Quantitatively dissolve an accurately weighed quantity of benzene in dimethyl sulfoxide to obtain a solution having a concentration of about 1.0 mg per mL. Dilute this solution quantitatively, and stepwise if necessary, with organic-free water (see Residual Solvents 467) to obtain a solution having a concentration of about 0.1 µg per mL.
Test solution— Transfer about 50 mg of Carbomer Homopolymer, accurately weighed, to a 10-mL volumetric flask. Add about 7.5 mL of sodium chloride solution (2 in 100), and mix by mechanical means until homogeneous (usually about 30 minutes). Dilute with sodium chloride solution (2 in 100) to volume, and mix until homogeneous (usually less than 1 minute). [note—This preparation must be analyzed within 3 hours of preparation.]
Reference solution— Transfer about 50 mg of Carbomer Homopolymer, accurately weighed, to a 10-mL volumetric flask. Add about 7.5 mL of sodium chloride solution (2 in 100), and mix by mechanical means until homogeneous (usually about 30 minutes). Add 1.0 mL of the Solvent solution, dilute with sodium chloride solution (2 in 100) to volume, and mix until homogeneous (usually less than 1 minute). This solution contains about 0.01 µg of benzene per mL.
Chromatographic system— Proceed as directed in the test for Limit of benzene under Carbomer Copolymer.
Procedure— Proceed as directed in the test for Limit of benzene under Carbomer Copolymer. The response of the benzene peak obtained from the Test solution is not greater than half of the benzene peak response obtained from the Reference solution:NF27 not more than 0.0002% is found.
Change to read:
Limit of acrylic acid—
0.01 M Phosphate buffer— Dissolve 1.361 g of monobasic potassium phosphate in 1000 mL of water, and mix.
Solution A— Use 0.01 M Phosphate buffer.
Solution B— Prepare a filtered and degassed mixture of 0.01 M Phosphate buffer and acetonitrile (1:1, v/v).
Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Solvent— Dissolve 25 g of potassium alum in 1000 mL of water, and mix.
Standard solution— Dissolve an accurately weighed quantity of acrylic acid in the Solvent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a concentration of about 12.5 µg per mL.
Test solution— Mix about 100 mg of Carbomer Homopolymer, accurately weighed, with Solvent, and add Solvent to obtain 20.0 mL of suspension. Heat the suspension at 50 for 20 minutes with occasional shaking. Then shake the suspension continuously at room temperature for 60 minutes. Centrifuge and use the clear supernatant.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 205-nm detector and a 4.6-mm × 12-cm column that contains packing L1. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)		 Solution A
(%)		 Solution B
(%)		 Elution
0 100 0 equilibration
0–8 100 0 isocratic
8–9 100®0 0®100 linear gradient
9–20 0 100 isocratic
20–21 0®100 100®0 linear gradient
21–30 100 0 isocratic
Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the response for the acrylic acid peaks. Calculate the percentage of free acrylic acid in the portion of Carbomer Homopolymer taken by the formula:
100(V/1000)(C/W)(rU / rS)NF27
in which V is the volume, in mL, of the Test solution; 1000 is the conversion factor converting mg to µg;NF27 C is the concentration, in µg per mL, of acrylic acid in the Standard solution; W is the weight, in mg, of Carbomer Homopolymer taken to prepare the Test solution; and rU and rS are the acrylic acid responses obtained from the Test solution and the Standard solution, respectively: not more than 0.25% is found.
Content of carboxylic acid— Proceed as directed in the test for Content of carboxylic acid under Carbomer Copolymer, except to calculate the percentage of carboxylic acid in the portion of Carbomer Homopolymer taken by the formula:
100(45.02VN/W)
in which W is the weight, in mg, of the portion of Carbomer Homopolymer taken; and the other terms are as defined therein.
1  Available as a Brookfield RV viscometer, or the equivalent.NF27
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Topic/Question Contact Expert Committee
Monograph Hong Wang, Ph.D.
Scientist
1-301-816-8351		 (EM205) Excipient Monographs 2
USP32–NF27 Page 1190
Pharmacopeial Forum: Volume No. 34(1) Page 136
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.