Carbamazepine 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

Carbamazepine Tablets contain NLT 92.0% and NMT 108.0% of the labeled amount of carbamazepine (C₁₅H₁₂N₂O).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M

Sample solution: Nominally 250 mg of carbamazepine from powdered Tablets in 15 mL of acetone

Analysis: Boil the Sample solution for 5 min in a suitable beaker. Filter while hot, using two 5-mL portions of hot acetone to effect transfer.

Evaporate the filtrate with the aid of nitrogen to 5 mL, and cool in an ice bath until crystals are formed. Filter the crystals, wash with 3 mL of cold acetone, and dry under vacuum at 70° for 30 min. Use the crystals.

Acceptance criteria: Meet the requirements

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

3 ASSAY

PROCEDURE

Mobile phase: Methanol, tetrahydrofuran, and water (12:3:85). Add 0.22 mL of formic acid and then 0.5 mL of triethylamine to each L.

Diluent: Methanol and water (50:50)

System suitability stock solution: 0.1 mg/mL of USP Carbamazepine RS and 0.5 mg/mL of USP Carbamazepine Related Compound A RS in methanol. Sonication may be used to aid in dissolution.

System suitability solution: 0.01 mg/mL of USP Carbamazepine RS and 0.05 mg/mL of USP Carbamazepine Related Compound A RS from System suitability stock solution in Diluent

Standard stock solution: 2 mg/mL of USP Carbamazepine RS in methanol. Sonication may be used to aid in dissolution.

Standard solution: 0.2 mg/mL of USP Carbamazepine RS from Standard stock solution in Diluent

Sample stock solution: Nominally 2 mg/mL of carbamazepine from NLT 20 Tablets prepared as follows. Finely powder the Tablets, and transfer a portion of the powder to a suitable volumetric flask. Add 80% of the final flask volume of methanol, sonicate for 15 min, and allow to cool to room temperature. Dilute with methanol to volume. Pass through a suitable filter and discard the first few mL of filtrate.

Sample solution: Nominally 0.2 mg/mL of carbamazepine from Sample stock solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.0- or 4.6-mm x 25-cm; 7-um packing L10

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 1.6 times the retention time of carbamazepine

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 3 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.7 between carbamazepine related compound A and carbamazepine, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) 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 USP Carbamazepine RS in the Standard solution (mg/mL)

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

Acceptance criteria: 92.0%-108.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

For products labeled as 100-mg chewable Tablets

Test 1: if the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1.

Medium: Water containing 1% sodium lauryl sulfate: 900 ml.

Apparatus 2: 75 rpm

Time: 60 min

Standard solution: USP Carbamazepine RS in Medium. [NOTE-A volume of methanol NMT 1% of the final total volume of the Standard solution may be used to dissolve the carbamazepine.]

Sample solution: Filtered portion of the solution under test, diluted with Medium if necessary

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 288 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved:

Result (A/A) xCxVx (1/L) x 100

A absorbance of the Sample solution

A absorbance of the Standard solution

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

V volume of the Medium, 900 mL

L label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of carbamazepine (CH, NO) is dissolved. Use Dissolution (711), Acceptance Table 1 with the following exceptions: at S.,, no unit is less than 0-5%; at S, no unit is less than 0-10%; and NMT 2 of the 24 units are less than Q-5%.

For products labeled as 200-mg Tablets

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

Medium, Apparatus 2, Standard solution, Sample solution, and Instrumental conditions: Proceed as directed in Test 1.

Times: 15 and 60 min

Analysis

Calculate the concentration (C) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (1):

Result = (A_U/A_S) x C_S

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)

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (1):

Result₁ = C₁x Vx (1/L) x 100

Result₂ = [(CxV)+(C₁xV_S)]x (1/L) x 100

C_i = concentration of carbamazepine in the portion of sample withdrawn at the specified time point (1) (mg/ml.)

V = volume of the Mediurn, 900 mL

L = label claim (mg/Tablet) L = 1

V₂ = volume of the Medium at time point 2 (mL)

V_S = volume of the Sample solution withdrawn at each time point (i) (mL)

Tolerances: See Table 1.

Table 1

Use Dissolution (711). Accentance Table 2 with the following exceptions. At 15 min: at L ₂ unit is more than 5% outside the stated range; at L₃ no unit is more than 10% outside the stated range; and NMT 2 of the 24 units are more than 5% outside the stated range.

At 60 min: at L₂ no unit is less than Q - 5%; at L₃ unit is less than Q - 10% and NMT 2 of the 24 units are less than Q + (- 5)%

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

Medium, Apparatus 2, Standard solution, Sample solution, and Instrumental conditions: Proceed as indicated in Test 1.

Times: 15 and 60 min

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C) of carbamazepine (C₁₅H₁₂N₂O) the sample withdrawn from the vessel at each time point (i): Result = (A_U/A_S) x C_S

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 / m * L)

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (1):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = [(C₂xV₂) + (C₁xV_S) x (1/L) x 100

C_i = concentration of carbamazepine in the portion of sample withdrawn at the specified time point (i) (mg / m L)

v = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V₂ = volume of the Medium at time point 2 (mL)

V_S = volume of the Sample solution withdrawn at each time point (i) (mL)

Tolerances: See Table 2.

Table 2

Use Dissolution (711), Acceptance Table 2 with the following exceptions. At 15 min: at L₂ unit is more than 5% outside the stated range; at L₃ unit is more than 10% outside the stated range; and NMT 2 of the 24 units are more than 5% outside the stated range. At 60 min: L₂, no unit is less than Q + (- 5)% at L₃; no unit is less than Q - 10% and NMT 2 of the 24 units are less than Q + (- 5)%.

Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Medium: Water containing 1% sodium dodecyl sulfate: 900 mL

Apparatus 2: 75 rpm

Time: 45 min

Standard stock solution: 0.9 mg/mL of USP Carbamazepine RS in methanol. Sonicate to dissolve as needed.

Standard solution: 9 µg/mL of USP Carbamazepine RS from Standard stock solution in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size and discard the first 3 mL of the filtrate. Dilute with Medium to a concentration similar to that of the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 288 nm

Cell length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved:

Result = (A_U/A_S) xC_SxDxVx (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)

D = dilution factor

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) is dissolved. (RB 22-Sep-2022)

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase, Diluent, and System suitability solution: Proceed as directed in the Assay.

Standard stock solution: 0.02 mg/mL each of USP Carbamazepine RS, USP Carbamazepine Related Compound B RS, and USP 9-Methylacridine RS in methanol. Sonication may be used to aid in dissolution.

Standard solution: 0.001 mg/mL each of USP Carbamazepine RS, USP Carbamazepine Related Compound B RS, and USP 9-Methylacridine

RS from Standard stock solution in Diluent

Sample solution: Nominally 1 mg/mL of carbamazepine from NLT 20 Tablets prepared as follows. Finely powder the Tablets, and transfer a portion of the powder to a suitable volumetric flask. Add about 50% of the final flask volume of Diluent, sonicate for 15 min, and allow to cool to room temperature. Dilute with Diluent to volume. Pass through a suitable filter and discard the first few mL of filtrate.

Chromatographic system: Proceed as directed in the Assay except use a Run time of NLT 3.5 times the retention time of carbamazepine.

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 3 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.7 between carbamazepine related compound A and carbamazepine, System suitability solution

Relative standard deviation: NMT 10.0% each for carbamazepine, carbamazepine related compound B, and 9-methylacridine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carbamazepine related compound B and 9-methylacridine in the portion of Tablets taken.

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of carbamazepine related compound B or 9-methylacridine from the Sample solution

r_S = peak response of carbamazepine related compound 8 or 9-methylacridine from the Standard solution

C_S = concentration of USP Carbamazepine Related Compound B RS or USP 9-Methylacridine RS in the Standard solution (mg/mL)

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

Calculate the percentage of other degradation products in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of any individual 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 / m L)

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

Acceptance criteria: See Table 3. Disregard peaks below 0.05%.

Table 3

^a This is a process impurity that is controlled in the drug substance. It is not to be reported or included in the total degradation products.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, preferably of glass. Protect from light and moisture. Store at controlled room temperature.

LABELING: The labeling indicates the Dissolution test with which the product complies.

USP REFERENCE STANDARDS (11).

USP Carbamazepine RS

USP Carbamazepine Related Compound A RS

10,11-Dihydrocarbamazepine.

C₁₅H₁₄N₂O   238.29

USP Carbamazepine Related Compound B RS

5H-Dibenz[b,flazepine.

C₁₄H₁₁N     193.25

USP 9-Methylacridine RS

9-Methylacridine.

C₁₄H₁₁N    193.25