Carbamazepine Extended-Release Capsules

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

Carbamazepine Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of carbamazepine (C₁₅H₁₂N₂O).

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. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: Water, triethylamine, and phosphoric acid (100: 0.1: 0.1)

Solution B: Methanol

Mobile phase: See Table 1.

Standard solution: 0.08 mg/mL of USP Carbamazepine RS in methanol

Sample solution: 0.08 mg/mL of carbamazepine in methanol. Pass a portion of the solution through a suitable filter, discarding the first 3 mL of filtrate.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carbamazepine (C₁₅H₁₂N₂O) in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of carbamazepine from the Sample solution

r_S = peak response of carbamazepine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.05 M phosphate buffer, pH 6.8 (dissolve 6.8 g of potassium phosphate monobasic and 0.8 g of sodium hydroxide in 1000 mL of water, adjust with 1 N sodium hydroxide or with phosphoric acid to a pH of 6.8); deaerated. See Table 2.

Apparatus 2: 75 rpm, with apex vessels

Times: 1, 4, and 8 h

Standard stock solution: 1 mg/mL of USP Carbamazepine RS in methanol

Standard solution: Prepare a solution of USP Carbamazepine RS in Medium as directed in Table 3.

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 285 nm, with a background correction at 490 nm

Cell: 0.05-cm flow cell

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result = (A_U/A_S ) × C_S × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Carbamazepine RS in the Standard solution (mg/mL) (see Table 3)

V = volume of Medium (see Table 2)

L = label claim for carbamazepine (mg/Capsule)

Tolerances: See Table 4.

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: Methanol, tetrahydrofuran, and water (17:3:80). To each liter of this solution add 5 mL of triethylamine and 2 mL of formic acid.

Solution B: Methanol, tetrahydrofuran, and water (77:3:20). To each liter of this solution add 2.5 mL of triethylamine and 1 mL of formic acid.

Mobile phase: See Table 5.

System suitability solution: 4 mg/mL of USP Carbamazepine RS and 0.004 mg/mL of USP Carbamazepine Related Compound A RS in methanol

Sensitivity solution: 0.002 mg/mL of USP Carbamazepine RS in methanol

Standard solution: 0.004 mg/mL of USP Carbamazepine RS and 0.008 mg/mL of USP Carbamazepine Related Compound B RS in methanol

Sample solution: Nominally 4 mg/mL of carbamazepine from Capsules prepared as follows. Transfer a portion of the contents from

Capsules (NLT 20) to a suitable volumetric flask and add 80% of the flask volume of methanol. Sonicate with occasional shaking for NLT 20 min and dilute with methanol to volume. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 3 mL of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 25-cm; 5-μm packing L7

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note—The relative retention times in Table 6 are provided as information that could aid in peak assignment.]

Suitability requirements

Resolution: NLT 2.0 between carbamazepine and carbamazepine related compound A, System suitability solution

Relative standard deviation: NMT 5.0% for carbamazepine and carbamazepine related compound B, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carbamazepine related compound B in the portion of Capsules taken

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of carbamazepine related compound B from the Sample solution

r_S = peak response of carbamazepine related compound B from the Standard solution

C_S = concentration of USP Carbamazepine Related Compound B RS in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified degradation product in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of each unspecified degradation product from the Sample solution

r_S = peak response of carbamazepine from the Standard solution

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

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

Acceptance criteria: See Table 7. The reporting threshold is 0.05%.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Carbamazepine RS

USP Carbamazepine Related Compound A RS

10,11-Dihydro-5H-dibenz[b,f]azepine-5-carboxamide.

C₁₅H₁₄N₂O 238.29

USP Carbamazepine Related Compound B RS

5H-Dibenz[b,f]azepine.

C₁₄H₁₁N 193.25 (USP 1-Dec-2024)