Oxcarbazepine Oral Suspension

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

Oxcarbazepine Oral Suspension contains NLT 95.0% and NMT 105.0% of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂).

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

Change to read:

3.1 PROCEDURE

Protect all solutions from light.

Buffer: Dissolve 1.36 g of sodium acetate (RB 1-Oct-2024) and 0.6 g of glacial acetic acid in 1 L of water. Adjust with glacial acetic acid to a pH of 4.4.

Solution A: Acetonitrile, tetrahydrofuran, tert-butyl methyl ether, and Buffer (130:30:9:830)

Solution B: Acetonitrile, tetrahydrofuran, tert-butyl methyl ether, and Buffer (670:30:9:290)

Mobile phase: See Table 1.

Table 1

Diluent: Dissolve 0.1 g of ascorbic acid and 1 mL of acetonitrile in 1 L of water.

Standard stock solution: 1 mg/mL of USP Oxcarbazepine RS in acetonitrile. Sonicate to aid in dissolution.

Standard solution: 0.25 mg/mL of USP Oxcarbazepine RS from the Standard stock solution, prepared as follows. Dilute a suitable volume of the Standard stock solution first with Diluent, using 70% of the final volume. Allow the solution to equilibrate to room temperature, and then dilute with acetonitrile to volume.

System suitability stock solution: 0.01 mg/mL of USP Oxcarbazepine Related Compound A RS and 0.02 mg/mL of USP Oxcarbazepine Related Compound C RS in acetonitrile

System suitability solution: 0.5 µg/mL of USP Oxcarbazepine Related Compound A RS and 1 µg/mL of USP Oxcarbazepine Related Compound C RS from the System suitability stock solution, in Standard solution

Sample solution: 0.25 mg/mL of oxcarbazepine from a portion of Oral Suspension, prepared as follows. Dissolve first with Diluent using 8% of the final volume, and then fill to 30% of the final volume with acetonitrile. Sonicate for 15 min. Add Diluent to fill to 36% of the final volume. Shake the flask vigorously. Allow the solution to equilibrate to room temperature, and dilute with Diluent to volume.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 210-400 nm.

Column: 3.0-mm × 25-cm; 3-µm packing L1

Column temperature: 50°

Flow rate: 0.6 mL/min

Injection volume: 5 µL

3.3 System suitability

Samples: Standard solution and System suitability solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.3 between oxcarbazepine related compound C and oxcarbazepine related compound A, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) in the portion of Oral Suspension taken:

Result = (r_U/r_S) x (C_S/C_U) x  100

r_U = peak response of oxcarbazepine from the Sample solution

r_S = peak response of oxcarbazepine from the Standard solution

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

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

Acceptance criteria: 95.0%-105.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: 1% sodium dodecyl sulfate in water: 890 mL

Apparatus 2: 75 rpm

Time: 30 min

Analysis: Shake manually a bottle of Oral Suspension for about 20 s. Using a 10-mL syringe, draw 10.0 mL of the Oral Suspension. Attach a long needle to the syringe. Deliver carefully 10.0 mL of Oral Suspension through the needle to the bottom of the vessel containing preheated Medium. Take about 10 mL of the Medium from the vessel to clean the syringe, and transfer it back to the vessel. Start the paddle rotation immediately after introduction of each sample.

Mobile phase: Methanol, glacial acetic acid, and water (24:1:75)

Standard solution: 0.7 mg/mL of USP Oxcarbazepine RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 1-µm pore size, discarding the first few milliliters.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 310 nm

Column: 4.6-mm × 25-cm; 10-µm packing L10

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

L = label claim (mg in 10 mL)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) is dissolved.

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

Medium: 7.5 g/L of sodium dodecyl sulfate in water; 890 mL, deaerated

Apparatus 2: 75 rpm

Time: 15 min

Mobile phase: Methanol, glacial acetic acid, and water (24:1:75)

Standard solution: 0.7 mg/mL of USP Oxcarbazepine RS prepared as follows. Transfer a suitable amount of USP Oxcarbazepine RS to a suitable volumetric flask. Add 20% of the final volume of acetonitrile and sonicate for 10 min with frequent vortexing. Add 50% of the final volume of Medium and sonicate again for 10 min with frequent vortexing. Make sure USP Oxcarbazepine RS is fully dissolved at room temperature. If not fully dissolved, sonicate for an additional 10 min or until completely dissolved. Dilute with Medium to volume and mix well. Pass a portion of the solution through a suitable filter of 1-µm pore size, discarding the first few milliliters. [NOTE-Immediately keep it at 10° for the Analysis. This solution is stable for 24 h at 10°.]

Sample solution: Use a separate bottle of Oral Suspension for each vessel. After the dissolution Medium has reached the appropriate temperature, remove about 10 mL of heated Medium from each vessel and set aside for cannula rinsing after sample introduction. Shake manually a bottle of Oral Suspension for about 20 s. Using a 10-mL syringe, draw 10.0 mL of the Oral Suspension. Wipe the syringe with paper towels to remove excess Oral Suspension that may stick to the outside of the syringe. Attach a suitable cannula to the syringe. Deliver carefully 10.0 mL of Oral Suspension through the cannula to the bottom of the vessel. Start the paddle rotation immediately after introduction of each sample. Rinse the cannula into the vessel with 10 mL of the previously removed Medium. Pass a portion of the solution under test through a suitable filter of 1-µm pore size, discarding the first few milliliters. [NOTE-The plunger of the syringe should be pushed at a consistent rate and sample delivery should be completed in about 15 s.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 310 nm

Column: 4.6-mm x 25-cm; 10-µm packing L10

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of oxcarbazepine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved:

Result = (r_U/r_S) x (C_S) x (1/L) x V x 100

r_U = peak response of oxcarbazepine from the Sample solution

r_S = peak response of oxcarbazepine from the Standard solution

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

L = label claim (mg in 10 mL)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) is dissolved.

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

Protect solutions containing oxcarbazepine from light.

Medium: Dissolve 8 g of sodium dodecyl sulfate in 1000 mL of water; 890 mL, deaerated by sonication.

Apparatus 2: 50 rpm

Time: 20 min

Mobile phase: Methanol, glacial acetic acid, and water (24:1:75)

Standard solution: 0.7 mg/mL of USP Oxcarbazepine RS prepared as follows. Transfer a quantity of USP Oxcarbazepine RS to an appropriate volumetric flask and dissolve in 20% of the flask volume of acetonitrile. Sonicate to dissolve, if necessary. Dilute with Medium to volume.

[NOTE-The Standard solution may be stable for 48 h at 10°.]

Sample solution: After the Medium has reached the appropriate temperature, remove about 10 mL of Medium from each vessel and set aside. Determine the density, d (g/mL), of the Oral Suspension using appropriate means. Shake manually a bottle of Oral Suspension for about 20 s. Collect 10 mL of the Oral Suspension using a suitable syringe. Clean the syringe from outside and weigh. Attach a cannula to the syringe. Start the dissolution test apparatus and deliver immediately 10 mL of Oral Suspension through the cannula into each vessel to a zone that is between the surface of the Medium and the top of the rotating paddle blade. Add 10 mL of the previously withdrawn dissolution Medium with the help of same cannula to each vessel. Weigh the syringe again and determine the weight, W (g), of suspension delivered into each vessel. After completing the specified time, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

[NOTE-The Sample solution may be stable for 48 h at 10°.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 310 nm

Column: 4.6-mm × 25-cm; 5-µm packing L10

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved:

Result = (r_U/r_S) x C_S x V x (d/W) x (1/L) x 100

r_U = peak response of oxcarbazepine from the Sample solution

r_S = peak response of oxcarbazepine from the Standard solution

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

V = sum of the volume of Medium and the volume of Oral Suspension taken, 900 mL

d = density of the Oral Suspension (g/mL)

W = weight of the Oral Suspension taken (g)

L = label claim of Oral Suspension (mg/mL)

Tolerances: NLT 80% (Q) of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) is dissolved.

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

Protect solutions containing oxcarbazepine from light.

Medium: 0.75% sodium dodecyl sulfate in water (Add 7.5 g of sodium dodecyl sulfate into 1000 mL of water. Sonicate to dissolve.); 890 mL

Apparatus 2: 50 rpm

Time: 15 min

Buffer: Dissolve 2.72 g of sodium acetate and 1.5 mL of glacial acetic acid in 2000 mL of water. Sonicate to dissolve. Adjust with glacial acetic acid to a pH of 4.4.

Solution A: Add 20 mL of tert-butyl methyl ether to the Buffer.

Solution B: Acetonitrile

Mobile phase: See Table 2.

Table 2

Standard solution: 0.7 mg/mL of USP Oxcarbazepine RS prepared as follows. Transfer a quantity of USP Oxcarbazepine RS to an appropriate volumetric flask and dissolve in 2% of the flask volume of Dimethyl sulfoxide. Sonicate for 5 min. Add 60% of the flask volume of Medium. Sonicate to dissolve, if necessary. Dilute with Medium to volume.

Sample solution: Use a separate bottle of Oral Suspension for each vessel. Determine the density, d (g/mL), of the Oral Suspension using appropriate means. Shake manually a bottle of Oral Suspension for about 20 s. Collect 10 mL of the Oral Suspension using a suitable syringe and weigh. Attach a cannula to the syringe. Deliver carefully 10 mL of Oral Suspension through the cannula to the bottom of each vessel containing the preheated Medium. Withdraw 10 mL of Medium from the vessel to clean the cannula and transfer it back to the vessel. Start the dissolution test apparatus immediately. Weigh the syringe again and determine the weight, W (g), of suspension delivered into each vessel. After completing the specified time, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 310 nm

Column: 4.6-mm x 15-cm; 5-µm packing L11

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved:

Result = (r_U/r_S) x C_S x V x (d/W) x (1/L) x 100

r_U = peak response of oxcarbazepine from the Sample solution

r_S = peak response of oxcarbazepine from the Standard solution

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

V = sum of the volume of Medium and the volume of Oral Suspension taken, 900 mL

d = density of the Oral Suspension (g/mL)

W = weight of the Oral Suspension taken (g)

L = label claim of Oral Suspension (mg/mL)

Tolerances: NLT 80% (Q) of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) is dissolved. (RB 1-Oct-2024)

4.2 DELIVERABLE VOLUME (698)

Meets the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

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Solution A, Solution B, Mobile phase, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 0.5 mg/mL of USP Carbamazepine RS in acetonitrile. Sonicate to aid in dissolution.

Standard solution: 0.5 µg/mL of USP Carbamazepine RS from the Standard stock solution prepared as follows. Dilute a volume of the Standard stock solution first with Diluent, using 70% of the final volume. Cool to room temperature, and dilute with acetonitrile to volume.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.3 between oxcarbazepine related compound C and oxcarbazepine related compound A peaks, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Oral Suspension taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each individual impurity 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 oxcarbazepine in the Sample solution (mg/mL)

F = relative response factor (see Table 3 (RB 1-Oct-2024))

Acceptance criteria: See Table 3.

Table 3 (RB 1-Oct-2024)

^a Acridine-9-carboxylic acid.

^b 10,11-Dioxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

^c For system suitability purposes only.

^d 5H-Dibenzo[b,f]azepine-10,11-dione.

^e Acridine.

^f 10(11H)-Oxo-5H-dibenz[b,f]azepine.

6 SPECIFIC TESTS

6.1 PH (791)

2.5-3.7

6.2 MICROBIAL ENUMERATION TESTS (61) and TEST FOR SPECIFIED MICROORGANISMS (62)

The total aerobic microbial count is NMT 10² cfu/mL. The total yeasts and molds count is NMT 10¹ cfu/mL. It meets the requirements of the test for absence of Escherichia coli.

7 ADDITIONAL REQUIREMENTS

7.1 PACKAGING AND STORAGE

Store at controlled room temperature.

7.2 LABELING

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

7.3 USP REFERENCE STANDARDS (11)

USP Carbamazepine RS

USP Oxcarbazepine RS

USP Oxcarbazepine Related Compound A RS

N-Formyl-10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

C₁₆H₁₂N₂O₃ 280.28

USP Oxcarbazepine Related Compound C RS

Acridin-9(10H)-one.

C₁₃H₉NO 195.22