Felbamate 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

Felbamate Oral Suspension is a viscous liquid containing NLT 90.0% and NMT 110.0% of the labeled amount of felbamate (C₁₁H₁₄N₂O₄). The product may contain suitable preservatives.

2 IDENTIFICATION

Change to read:

A. The retention time of the major peak of (USP 1-Dec-2020) the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

B. The UV spectrum of the felbamate peak in the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-Dec-2020)

3 ASSAY

Change to read:

PROCEDURE

Buffer: 28.5 g/L of tribasic sodium phosphate (USP 1-Dec-2020) in water

Mobile phase: Acetonitrile and Buffer (23:77). Adjust with phosphoric acid to a pH of 9.9.

Diluent A: Methanol and water (50:50) (USP 1-Dec-2020)

Diluent B: Acetonitrile and water (23:77)

System suitability solution: 160 µg/mL (USP 1-Dec-2020) of USP Felbamate RS and 20 µg/mL (USP 1-Dec-2020) of USP Felbamate Related Compound A RS in Diluent B and methanol prepared as follows. Transfer suitable amounts of USP Felbamate RS and USP Felbamate Related Compound A RS to an appropriate volumetric flask. Dissolve in 8% of the flask volume of methanol (USP 1-Dec-2020) Dilute with Diluent B to volume.

Standard solution: 160 µg/mL (USP 1-Dec-2020) of USP Felbamate RS prepared as follows. Transfer a suitable amount of USP Felbamate RS to (USP 1-Dec-2020) a suitable volumetric flask containing 16% of the flask volume of Diluent A. Add 50% of the flask volume of Diluent B. Sonication may be used to aid dissolution. Dilute with Diluent B to volume.

Sample stock solution: Nominally 1 mg/mL of felbamate in Diluent A prepared as follows. Transfer an amount of the Oral Suspension to a suitable volumetric flask. Add 60% of the flask volume of Diluent A, and sonicate for 15 min. Shake mechanically for 30 min, and dilute with Diluent A to volume.

Sample solution: Nominally 160 µg/mL (USP 1-Dec-2020) of felbamate from Sample stock solution in Diluent B. Pass through a filter with a pore size of 0.45-µm. (USP 1-Dec-2020)

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identification B, use a diode array detector in the range of 190-400 nm. (USP 1-Dec-2020)

Column: 4.1-mm × 15-cm; 5-µm packing L21

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: (USP 1-Dec-2020) 20 μL

Run time: NLT 2 times the retention time of felbamate (USP 1-Dec-2020)

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

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

Tailing factor: NMT 1.5. (USP 1-Dec-2020) Standard solution

Relative standard deviation: NMT 1.0%, (USP 1-Dec-2020) Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of felbamate (C₁₁H₁₄N₂O₄) in the portion of Oral Suspension taken:

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

r_U = peak response of felbamate from the Sample solution

r_S = peak response of felbamate from the Standard solution

C_S = concentration of USP Felbamate RS in the Standard solution (µg/mL) (USP 1-Dec-2020)

C_U = nominal concentration of felbamate in the Sample solution (µg/mL) (USP 1-Dec-2020)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

Medium: Water: 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Mobile phase: Acetonitrile and water (35:65)

System suitability stock solution: 0.1 mg/mL of USP Methylparaben RS in methanol

System suitability solution: 0.1 mg/mL of USP Methylparaben RS from System suitability stock solution and 0.4 mg/mL of USP Felbamate RS prepared as follows. Transfer 40 mg of USP Felbamate RS to a 100-mL volumetric flask. Add 10 mL of System suitability stock solution and sonicate for 5 min. Dilute with Medium to volume. (USP 1-Dec-2020)

Standard solution: (L/1000) mg/mL of USP Felbamate RS in Medium, where L is the (USP 1-Dec-2020) label claim in mg/mL.. An amount of methanol, not exceeding 10% of the final volume, can be used to help in solubilizing felbamate.

Sample solution: Using a syringe, accurately weigh by difference approximately 5 mL of the well-mixed Oral Suspension. Introduce the sample into the dissolution vessel with the paddles rotating, and avoid getting the sample on the paddle or shaft. At the time specified, withdraw an aliquot of the solution under test, and pass through a suitable filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 10-um packing L7

Flow rate: 2 mL/min

Injection volume

OFFI Run time: NLT 3.5 times the retention time of felbamate (USP 1-Dec-2020)

System suitability: 25 µL

Analysis: 15 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for felbamate and methylparaben are about 1.0 and 1.5, respectively.]

Suitability requirements

Resolution: NLT 2.0 between methylparaben and felbamate, System suitability solution

Tailing factor: NMT 2, Standard solution

Relative standard deviation: NMT 2%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of felbamate (C₁₁H₁₄N₂O₄) dissolved:

Result = (r_U/r_S) x C_S x V x (d/W) x (1/L) x 100 (USP 1-Dec-2020)

r_U = peak response of felbamate from the Sample solution

r_S = peak response of felbamate from the Standard solution

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

V = volume of Medium, 900 mL

d (USP 1-Dec-2020) = density of the Oral Suspension (g/mL)

W = weight of the Oral Suspension taken (g)

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

Tolerances: NLT 80% (Q) of the labeled amount of felbamate (C₁₁H₁₄N₂O₄) is dissolved.

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

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

System suitability solution: 200 µg/mL (USP 1-Dec-2020) of USP Felbamate RS and 20 µg/mL (USP 1-Dec-2020) of USP Felbamate Related Compound A RS in Diluent B prepared as follows. Transfer suitable quantities of USP Felbamate RS and USP Felbamate Related Compound A RS into a suitable volumetric flask. Dissolve in 8% of the flask volume of methanol. Dilute with Diluent B to volume.

Standard stock solution: 200 µg/mL (USP 1-Dec-2020) of USP Felbamate RS in Diluent A

Standard solution: 0.2 µg/mL of USP Felbamate RS from Standard stock solution in Diluent B prepared as follows. Transfer a suitable volume of Standard stock solution to a suitable volumetric flask containing 0.8% of the flask volume of methanol, and dilute with Diluent B to volume.

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for relative retention times.]

Suitability requirements

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

Tailing factor: NMT 2.0 for the felbamate peak, Standard solution

Relative standard deviation: NMT 10% for the felbamate peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of felbamate from the Standard solution

C_S = concentration of USP Felbamate RS in the Standard solution (µg/mL)

C_U = nominal concentration of felbamate in the Sample solution (µg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 2-Phenylpropane-1,3-diol.

6 SPECIFIC TESTS

Change to read:

6.1 PH (791)

Sample solution: Use a portion of well-stirred Oral Suspension.

Acceptance criteria: 4.5-6.0 (USP 1-Dec-2020)

6.2 MICROBIAL ENUMERATION TESTS (61) and TESTS 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

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

7.2 USP REFERENCE STANDARDS (11)

USP Felbamate RS

USP Felbamate Related Compound A RS

3-Hydroxy-2-phenylpropyl carbamate.

C₁₀H₁₃NO₃ 195.22

USP Methylparaben RS