Carvedilol Tablets

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

Carvedilol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of carvedilol (C₂₄H₂₆N₂O₄).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970

Wavelength range: 250-400 nm

Cell: 0.2 cm

Sample solution: 0.125 mg/mL of carvedilol prepared as follows. Place 10 Tablets in a 150-mL polypropylene tube, and disintegrate the Tablets in methanol (100 mL for the Tablet strengths 3.125, 6.25, and 25 mg, and 50 mL for the Tablet strength 12.5 mg) using a mechanical homogenizer. Transfer the homogenate to an appropriate volumetric flask, and dilute with methanol to volume. Pass through a suitable PTFE filter of 0.45-µm pore size.

3 ASSAY

3.1 PROCEDURE

Buffer: Dissolve 0.7 g of anhydrous monobasic potassium phosphate in 500 mL of water, and add 10 mL of triethylamine. Adjust with phosphoric acid to a pH of 3.0 ± 0.1.

Mobile phase: Dissolve 1.04 g of sodium dodecyl sulfate in 150 mL of Buffer in a 2-L volumetric flask, and sonicate. Add 720 mL of acetonitrile, and dilute with water to volume. Pass through a nylon 66 filter of 0.2-µm pore size.

Diluent: Methanol and 1 M hydrochloric acid (9:1)

Methanol solution: Methanol and water (1:1)

Standard solution: 0.0125 mg/mL of USP Carvedilol RS prepared as follows. Dissolve a quantity of USP Carvedilol RS in a mixture of Diluent and water (9:1), and sonicate until the solution is clear. Dilute with Methanol solution to obtain the required final concentration.

Sample stock solution: Transfer a portion of the powdered Tablets (NLT 20), equivalent to 25 mg of carvedilol, to a 100-mL volumetric flask.

Add 10 mL of water, shake by hand, then add 70 mL of Diluent, and sonicate for 30 min. Shake on a mechanical shaker for about 30 min, and dilute with Diluent to volume to prepare a 0.25-mg/mL solution. Centrifuge an appropriate amount (about 50 mL) at 2000 rpm for 10 min.

Sample solution: 0.0125 mg/mL of carvedilol in Methanol solution from the Sample stock solution. Pass a portion of the solution through a suitable syringe filter of 0.45-µm pore size, discard the first 5 mL, and use the filtrate as the Sample solution.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 50-mm; packing L7

Column temperature: 40"

Flow rate: 1 mL/min

Run time: 30 min

Injection size: 25 µL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carvedilol (C₂₄H₂₆N₂O₄) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of the Sample solution (mg/ml.)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Test 1

Medium: 0.7% (7 mL/L) of hydrochloric acid, adjusted with 50% (w/w) sodium hydroxide to a pH of 1.45 ± 0.2; 900 mL; deaerated

Apparatus 2: 50 rpm

Time: 30 min.

Standard stock solution: Transfer about 7 mg of USP Carvedilol RS to a 250-ml, volumetric flask. Add 5 mL of methanol, and sonicate until dissolved. Cool to room temperature, dilute with Medium to volume, and mix well.

Standard solution: On the basis of the label claim and using the Standard stock solution, prepare a solution of USP Carvedilol RS in Medium having an appropriate concentration (C), as shown in Table 1.

Table 1

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size.

Analytical wavelengths: 285 and 380 nm

Path length: 1 cm

Blank: Medium

Analysis: Calculate the corrected absorbance of the Standard solution and the Sample solution:

А_corr = A₂₈₅ - A₃₈₀

А_corr = corrected absorbance of the Standard solution or the Sample solution

A₂₈₅ = absorbance of the Standard solution or the Sample solution at 285 nm

A₃₈₀ = absorbance of the Standard solution at 380 nm

Calculate the percentage of carvedilol dissolved:

Result = (A_U/A_S) x C_S x (V/L) x 100

A_U = corrected absorbance from the Sample solution

A_S = corrected absorbance from the Standard solution

C_S = corrected concentration of the Standard solution (mg/ml.)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of carvedilol (C₂₄H₂₆N₂O₄) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: Simulated gastric fluid without enzymes; 900 mL

Apparatus 2, Time, Standard stock solution, Standard solution, Sample solution, and Analysis: Proceed as directed in Test 1.

Tolerances: NLT 80% (0) of the labeled amount of carvedilol (C₂₄H₂₆N₂O₄) is dissolved.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: Simulated gastric fluid with pepsin, pH 1.45 (dissolve 12.0 g of sodium chloride and 19.2 g of purified pepsin (porcine origin, activity 800-2500 Units/mg of protein) in 18 mL of hydrochloric acid and sufficient water to make 6 L; adjust with hydrochloric acid to a pH of 1.45); 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 2.72 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.0 ± 0.05.

Mobile phase: Buffer and acetonitrile (650:350)

Standard stock solution: 1.4 mg/mL of USP Carvedilol RS in methanol

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the Tablet label claim, in mg.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 15-cm (ERR 1-Feb-2024): 5-um packing L7

Column temperature: 35"

Flow rate: 1.5 mL/min

Injection size: 20 μι

System suitability

Sample: Standard solution

Suitability requirements.

Column efficiency: NLT 3500 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis: Calculate the percentage of carvedilol dissolved.

Result = (r_U/r_S) × (C_S/L) × V × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of carvedilol (C₂₄H₂₆N₂O₄) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

Buffer, Mobile phase, Diluent, Methanol solution, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: 0.25 mg/mL of carvedilol prepared as follows. Place 1 Tablet into a volumetric flask of appropriate size, based on the label claim. Add water to the flask up to about 10% of volume, and shake by hand to disintegrate the Tablet. Fill the flask up to 75% of volume with Diluent, and sonicate for 30 min to obtain complete disintegration. Shake on a mechanical shaker for 30 min, allow to cool, and dilute with Diluent to volume. Centrifuge an appropriate amount of this solution for 10 min at 2400 rpm, and transfer 4 mL of supernatant into a 100-mL volumetric flask. Fill the flask to about 85% of volume with Methanol solution, and sonicate for 20 min, with intermittent shaking. Dilute with Methanol solution to volume, and pass through a suitable syringe filter of 0.45-µm pore size.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carvedilol (C₂₄H₂₆N₂O₄) in the Tablet taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of the Sample solution (mg/mL)

5 IMPURITIES

Organic Impurities

Buffer, Mobile phase, Diluent, Methanol solution, and Sample stock solution: Prepare as directed in the Assay.

Standard stock solution: Use the Standard solution from the Assay.

Standard solution: 1.25 μg/mL USP Carvedilol RS in a mixture of Diluent and water (1:1) from the Standard stock solution

Sample solution: Dilute with water to volume, 25 mL of the supernatant from the Sample stock solution in a 50-mL volumetric flask. Pass a portion of the solution through a suitable syringe filter of 0.45-μm pore size.

Chromatographic system: Proceed as directed in the Assay, except for Injection size.

Injection size: 15 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of carvedilol from the Standard solution

C_S = concentration of USP Carvedilol RS in the Standard solution (mg/mL)

C_U = nominal concentration of carvedilol in the Sample solution (mg/mL)

Acceptance criteria

Individual impurities: NMT 0.2% (specified or unspecified)

Total impurities: NMT 1.0%

[Note—Disregard any peaks with a relative retention time less than or equal to 0.04 and peaks with less than 0.05% of the nominal carvedilol

peak response in the Sample solution.]

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers protected from moisture. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Carvedilol RS