Phenytoin Chewable 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

Phenytoin Chewable Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of phenytoin (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.

3 ASSAY

Procedure

Solution A: Triethylamine and water (1:99)

Mobile phase: Methanol, acetonitrile, water, Solution A, and acetic acid (270:230:500:5:1)

Standard solution: 0.5 mg/mL of USP Phenytoin RS in Mobile phase

Sample solution: Nominally 0.5 mg/mL of phenytoin from NLT 20 finely powdered Chewable Tablets in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 25 μL

Run time: NLT 2 times the retention time of the phenytoin peak

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of phenytoin (C₁₅H₁₂N₂O₂) in the portion of Chewable Tablets taken:

Result = (r_U/r_S) × (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 Phenytoin RS in the Standard solution (mg/mL)

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

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Dissolve 6 g of tromethamine in 600 mL of water. Dilute with water to 1 L, and adjust with phosphoric acid to a pH of 9.0. Dissolve 10 g of sodium lauryl sulfate in 1 L of the prepared buffer; 900 mL.

Apparatus 2: 100 rpm

Time: 120 min

Solution A, Mobile phase, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 3.0 mg/mL of USP Phenytoin RS in methanol

Standard solution: 0.012 mg/mL of USP Phenytoin RS prepared as follows. Transfer a suitable volume of the Standard stock solution to a suitable volumetric flask, and dilute with Medium to volume to obtain an intermediate concentration of 0.06 mg/mL of USP Phenytoin RS.

Transfer a suitable volume of the resulting solution to a suitable volumetric flask, and dilute with Mobile phase to volume.

Sample solution: Withdraw a portion of the solution under test and filter, discarding the first 3 mL of the filtrate. Pipet 10.0 mL of this solution into a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 70% (Q) of the labeled amount of phenytoin (C₁₅H₁₂N₂O₂) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: 6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.5.

Solution B: Acetonitrile and methanol (40:60)

Mobile phase: See Table 1.

Table 1

Diluent: Solution B and water (50:50)

Standard solution: 1 μg/mL of USP Phenytoin RS, 5 μg/mL of USP Phenytoin Related Compound A RS, and 9 μg/mL of USP Phenytoin Related Compound B RS in Diluent

Sample solution: Nominally 1000 μg/mL of phenytoin prepared as follows. Finely powder NLT 20 Chewable Tablets and transfer a portion of the powder to an appropriate volumetric flask. Add Diluent to about 50% of the final flask volume, and shake the mixture mechanically for 15 min or until dissolved. Dilute with Diluent to volume, centrifuge, and use the supernatant. Pass a portion of the solution through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 3-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0% for the phenytoin peak

Signal-to-noise ratio: NLT 10 for the phenytoin peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phenytoin related compound A and phenytoin related compound B in the portion of Chewable Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of phenytoin related compound A or phenytoin related compound B from the Sample solution

r_S = peak response of phenytoin related compound A or phenytoin related compound B from the Standard solution

C_S = concentration of USP Phenytoin Related Compound A RS or USP Phenytoin Related Compound B RS in the Standard solution (μg/mL)

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

Calculate the percentage of any individual unspecified degradation product in the portion of Chewable Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

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

r_S = peak response of phenytoin from the Standard solution

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

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

Acceptance criteria: See Table 2. Disregard any degradation product less than 0.05%.

Table 2

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature. Protect from moisture.

Labeling: Label the Chewable Tablets to indicate that they are to be chewed before swallowing.

USP Reference Standards 〈11〉

USP Phenytoin RS

USP Phenytoin Related Compound A RS

2,2-Diphenylglycine.

C₁₄H₁₃NO₂ 227.26

USP Phenytoin Related Compound B RS

2,2-Diphenyl-2-ureidoacetic acid.

C₁₅H₁₄N₂O₃ 270.28