Partially-Neutralized Methacrylic Acid and Ethyl Acrylate 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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Partially-neutralized poly(methacrylic acid, ethyl acrylate); 

Partially-neutralized methacrylic acid–ethyl acrylate copolymer 

CAS RN®: 25212-88-8. 

1 DEFINITION 

Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer consists of methacrylic acid and ethyl acrylate monomers arranged in a random distribution, some units of methacrylic acid in the copolymer are neutralized by sodium hydroxide. The non-neutralized methacrylic acid units in the partially-neutralized methacrylic acid and ethyl acrylate copolymer are NLT 43.2% and NMT 47.6%, calculated on the dried basis. It may contain suitable emulsifiers. 

2 IDENTIFICATION 

A. Infrared Absorption 

Sample: 100 mg of Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer 

Analysis: Dissolve the Sample in 1 mL of dehydrated alcohol, and place 2 drops of the solution on a sodium chloride (or potassium bromide) plate. Dry to evaporate the solvent and allow to form a film and cover with another sodium chloride (or potassium bromide) plate. Acceptance criteria: The IR absorption spectrum of Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer exhibits maxima corresponding to the same wavelengths as that of a similar preparation of USP Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer (1:1) RS, treated in the same manner. 

B. It meets the requirements of the Assay. 

3 ASSAY 

Procedure 

Sample: 1 g, calculated on the dried basis 

Analysis: Dissolve the Sample in 40 mL of water and 60 mL of 2-propanol, and titrate with 0.1 N sodium hydroxide VS, determining the endpoint potentiometrically (see Titrimetry 〈541〉). Each mL of 0.1 N sodium hydroxide is equivalent to 8.609 mg of methacrylic acid (C₄H₆O₂) units.  

Acceptance criteria: 43.2%–47.6% for Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer 

4 IMPURITIES 

Inorganic Impurities 

Residue on Ignition 〈281〉: 2.0%–3.5% 

Organic Impurities 

Procedure: Limit of Methacrylic Acid and Ethyl Acrylate 

Phosphoric acid solution: 0.1% phosphoric acid prepared from phosphoric acid 

Mobile phase: Methanol and Phosphoric acid solution (3:7) 

Standard solution: 1.0 µg/mL each of methacrylic acid and ethyl acrylate in methanol 

Sample solution: Transfer 0.5 g of Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer to a 25-mL volumetric ask, and dissolve in 20 mL of methanol. Add Phosphoric acid solution dropwise to precipitate the polymer while continuously stirring until the volume of 25 mL is reached. [Note—Stir with a magnetic stirrer for 10 min. Any volume deviation caused by the precipitation is negligible for contents in the ppm range. Use a magnetic stirrer of appropriate size to avoid a large variance from the nal volume of the Sample solution.] As soon as the solid matter has settled, pass the supernatant through a filter of 0.45-µm pore size. [Note—Solution that cannot be filtered is centrifuged at NLT 20,000 × g for NLT 30 min.] Use the clear supernatant. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 205 nm 

Column: 4.0-mm × 12.5-cm analytical column, 5-µm packing L1 or 4.6-mm × 15.0-cm analytical column, 5-µm packing L1 Flow rate: 1.2 mL/min 

Injection size: 20 µL 

[Note—Where appropriate, the volume must be adapted to the sensitivity of the detector.] 

[Note—Column switching system may be used for extension of column lifetime.] 

System suitability 

Sample: Standard solution 

[Note—The relative retention times for methacrylic acid and ethyl acrylate are 1.0 and 2.2, respectively.] 

Suitability requirements 

Resolution: NLT 5.0 between methacrylic acid and ethyl acrylate 

Relative standard deviation: NMT 5.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each monomer (methacrylic acid or ethyl acrylate) in the portion of Methacrylic Acid and Ethyl Acrylate Copolymer taken: 

Result = (r_U/r_S) × (C_S/W) × V_F × F × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

C_S = concentration of the Standard solution (µg/mL) 

W = weight of Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer taken to prepare the Sample solution (g) 

V_F = nal volume of the Sample solution, 25 mL 

F = conversion factor, 10−6 g/µg 

Acceptance criteria: NMT 0.01% for the total amount of monomers 

5 SPECIFIC TESTS 

Loss on Drying 〈731〉: Dry a sample at 110° for 6 h: it loses NMT 5.0% of its weight. 

Viscosity—Rotational Methods 〈912〉: Weigh 400 g of water into a short form, 600-mL beaker (internal diameter about 80 mm and height 120 mm). After determining the Loss on Drying, weigh a quantity of undried Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer, equivalent to 100 g on the dried basis. Transfer the sample to the beaker very slowly while effectively stirring (avoid lumps). Ensure that the stirring is very effective at the beginning and that the powder is immersed very slowly at the same time. Once the powder is dispersed and no lumps are visible, gentle stirring is then sufficient. Ensure a colloidal dispersion (milky white liquid) by stirring at room temperature for 3 h and taking care to avoid mixing in excess air. Afterwards allow the container to stand for 1 h, control the temperature to 23 ± 0.1°, and let the entrapped air dissipate. [Note—Ensure that the concentration of this solution is 20% (w/w).] Determine the viscosity of this solution at 23 ± 0.1° using a suitable rotational viscometer with a cylindrical spindle 1.9 cm in diameter and 6.5 cm high, attached to a shaft 0.3 cm in diameter.¹ The spindle rotates at 50 rpm at an immersion depth of 8.1 cm. Follow the instrument manufacturer's directions to measure the apparent viscosity. 

Acceptance criteria: 20–100 mPa · s 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature. 

Labeling: Label it to indicate the range of non-neutralized methacrylic acid units. The labeling also indicates the name and quantity of any emulsifier if the content is 0.10% or greater. 

USP Reference Standards 〈11〉 

USP Partially-Neutralized Methacrylic Acid and Ethyl Acrylate Copolymer (1:1) RS 

¹ A suitable spindle is available from Brookeld as an LV1 spindle, or the equivalent.