Carbomer Copolymer
(kar' boe mer koe pol' i mer).
» Carbomer Copolymer is a high molecular weight copolymer of acrylic acid and a long chain alkyl methacrylate cross-linked with allyl ethers of polyalcohols.
[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. ]
Packaging and storage— Preserve in tight containers, at a temperature not exceeding 45.
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, 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.
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: Add about 5 g of Carbomer Copolymer to 500 mL of water, and stir: a dispersion is formed, with a foam layer that persists after allowing the dispersion to stand at room temperature for 1 hour.
Viscosity 911 Carefully add 5.00 g of Carbomer Copolymer, previously dried in vacuum at 80 for 1 hour, to 500 mL of water in a 1000-mL beaker, while stirring continuously at 1000 ± 50 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. The stirrer used is a three-blade, 2-inch diameter marine impeller. Add the Carbomer Copolymer at a uniform rate over a period of 45 to 90 seconds, being sure that loose aggregates of powder are broken up, and continue stirring at 1000 ± 50 rpm for 15 minutes. Remove the stirrer, and place the beaker containing the dispersion in a 25 ± 0.1 water bath for 30 minutes. 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 potentiometrically (see Titrimetry 541) with a calomel–glass electrode system to a pH between 7.3 and 7.8 by adding sodium hydroxide solution (18 in 100) below the surface. Stir 2 to 3 minutes until neutralization is complete. Then determine the final pH. [note—If the pH is below 7.3, raise the pH with additional sodium hydroxide. If it is above 7.8, discard the mucilage, and prepare another batch, using a smaller amount of sodium hydroxide for titration. ] Return the beaker containing the neutralized mucilage to the 25 ± 0.1 water bath for 1 hour. Measure the pH again, making certain that the mucilage pH is between 7.3 and 7.8. Using a rotational viscometer equipped with a suitable spindle at a spindle immersion depth as defined in Table 1 (where A is the cylinder diameter, in cm; B is the cylinder height, in cm; C is the shaft diameter, in cm; D is the distance, in cm, from the top of the cylinder to the lower tip of the shaft; and E is the spindle immersion depth, in cm), perform the viscosity determination without delay to avoid the slight viscosity changes that occur 75 minutes after neutralization.
Table 1
Viscosity Ranges (mPa·s) Spindle No. A B C D E Multiplier
100–400 1 5.6 2.2 0.3 2.7 6.1 5
400–1600 2 4.7 0.2 0.3 2.7 4.9 20
1000–4000 3 3.5 0.2 0.3 2.7 4.9 50
2000–8000 4 2.7 0.2 0.3 2.7 4.9 100
4000–16,000 5 2.1 0.2 0.3 2.7 4.9 200
10,000–40,000 6 1.5 0.2 0.3 3.0 4.9 500
40,000–160,000 7 0.3 5.5 2,000
The spindle rotates at 20 rpm. Follow the instrument manufacturer's directions to measure the apparent viscosity. The viscosity value so obtained is within the limits specified in Table 2.
Table 2
Carbomer Copolymer 1% Viscosity Specification
(mPa·s)
A 4500–13,500
B 10,000–29,000
C 25,000–45,000
Loss on drying 731 Dry it in vacuum at 80 for 1 hour: it loses not more than 2.0% of its weight.
Limit of ethyl acetate and cyclohexane— [note—This test is required only for those Carbomer Copolymers where the 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 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 to obtain a solution containing 0.225 mg of ethyl acetate and 0.156 mg of cyclohexane.
Test solution— Transfer about 50 mg of Carbomer Copolymer, accurately weighed, to a 30-mL serum vial, add 20.0 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)— The gas chromatograph is equipped with a flame-ionization detector and a 2-mm × 3-m column packed with 1% liquid phase G25 on 60- to 80-mesh support S12. The carrier gas is helium, flowing at a rate of about 33 mL per minute. The column temperature is maintained at 115 for 4 minutes after injection, then the temperature is increased at a rate of 6 per minute to 175, and maintained at 175 for 5 minutes. The injection port and detector temperatures are maintained at 250. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between ethyl acetate and cyclohexane is not less than 1.0; and the relative standard deviation for replicate injections is not more than 2.5%. [noteFor information purposes only, the relative retention times are about 0.7 for methyl ethyl ketone, 0.9 for ethyl acetate, and 1.0 for cyclohexane. ]
Procedure— Separately inject equal volumes (about 2 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the percentages of ethyl acetate and cyclohexane in the portion of Carbomer Copolymer taken by the formula:
100(WS / WT)(RU / RS)
in which WS is the weight, in mg, of ethyl acetate or cyclohexane in the Standard solution; WT is the weight, in mg, of Carbomer Copolymer 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 peaks 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.
Limit of benzene—
Solvent solution— Dissolve an accurately weighed quantity of benzene quantitatively 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 Copolymer, 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 Copolymer, 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 (see Chromatography 621)— The gas chromatograph is equipped with a headspace injector, a flame-ionization detector, and a 0.53-mm × 30-m fused silica analytical column coated with a 3.0-µm G43 stationary phase. The carrier gas is helium flowing at a linear velocity of about 35 cm per second, and the split ratio is 1:5. The injection port and detector temperatures are maintained at 140 and 250, respectively. The chromatograph is programmed as follows: Initially the temperature of the column is maintained at 40 for 20 minutes after injection, then the temperature increased at a rate of 10 per minute to 240, and maintained at 240 for 20 minutes. [note—The following headspace conditions may be used: a pressurization time of 30 seconds and a transfer line temperature of 90. ] The vials are maintained at a temperature of 80 for 60 minutes prior to headspace injection. Chromatograph the Reference solution, and record the peak responses as directed for Procedure: the relative standard deviation for three replicate injections is not more than 15%.
Procedure— Transfer 10.0 mL each of the Reference solution and the Test solution to separate headspace vials. Close the vials with a tight rubber membrane stopper coated with polytetrafluoroethylene, and secure with an aluminum crimped cap. Shake to obtain a homogeneous dispersion. Separately inject equal volumes (about 1 mL) of the gaseous phase of the Reference solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the benzene peaks. 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: not more than 0.0002% is found.
Limit of acrylic acid—
pH 3.0 Phosphate buffer— Dissolve 6.80 g of monobasic potassium phosphate in about 300 mL of water, dilute with water to 500 mL, and mix. Dilute 100 mL of this solution with water to 1 L, adjust with phosphoric acid to a pH of 3.0 ± 0.1, and mix.
Mobile phase— Use filtered and degassed pH 3.0 Phosphate buffer.
Standard solution— Dissolve an accurately weighed quantity of acrylic acid in water, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.1 mg per mL. Dilute this solution quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 25 µg per mL.
Test solution— Transfer about 100 mg of Carbomer Copolymer, accurately weighed, to a tared serum vial. Add water to obtain about 10.0 mL of solution. Cap the vial, and shake by mechanical means for 2 hours. Add 2 drops of sodium hydroxide solution (5 in 10), and shake by hand for 15 seconds. Add 1.0 mL of calcium chloride solution (1 in 10), and shake until the gel collapses. Centrifuge for 15 minutes, and use the clear supernatant.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 200-nm detector and an 8-mm × 10-cm column that contains packing L1. The flow rate is about 1 mL per minute. 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 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the acrylic acid peaks. Calculate the percentage of free acrylic acid in the portion of Carbomer Copolymer taken by the formula:
100 (V / 1000) (C/W)(rU / rS)
in which V is the volume, in mL, of the Test solution; 1000 is the factor for converting mg to µg; C is the concentration, in µg per mL, of acrylic acid in the Standard solution; W is the weight, in mg, of Carbomer Copolymer taken to prepare the Test solution; and rU and rS are the acrylic acid peak responses obtained from the Test solution and the Standard solution, respectively: not more than 0.25% is found.
Content of carboxylic acid— Slowly add about 400 mg of Carbomer Copolymer, previously dried in vacuum at 80 for 1 hour and accurately weighed, to 400 mL of water in a 1000-mL beaker, while stirring continually at about 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 of the beaker. Continue stirring for 15 minutes. Reduce the stirring speed, and using a calomel–glass electrode system, titrate potentiometrically with 0.25 N sodium hydroxide VS (see Titrimetry 541). After each addition of 0.25 N sodium hydroxide VS, allow 1 minute for mixing before recording the pH. Calculate the percentage of carboxylic acid in the portion of Carbomer Copolymer taken by the formula:
100(45.02VN/W)
in which 45.02 is the molecular weight of the carboxylic acid (COOH) group; V is the volume, in mL, of sodium hydroxide consumed; N is the normality of the sodium hydroxide solution; and W is the weight, in mg, of Carbomer Copolymer taken. The carboxylic acid content is not less than 52.0% and not more than 62.0%.
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