Phenytoin Compounded Topical Gel

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Phenytoin Compounded Topical Gel contains NLT 95.0% and NMT 105.0% of the labeled amount of phenytoin (C₁₅H₁₂N₂O₂).

Prepare Phenytoin Compounded Topical Gel 10 mg/g to 50 mg/g as follows (see Pharmaceutical Compounding - Nonsterile Preparations 〈795〉). For Phenytoin Compounded Topical Gel containing 10 mg/g of phenytoin:

^a PCCA, Houston, TX.

For Phenytoin Compounded Topical Gel containing 50 mg/g of phenytoin:

^a PCCA, Houston, TX.

In an appropriately sized electronic mortar and pestle container, add Phenytoin, Polyethylene Glycol 300, and sufficient PCCA Spira-Wash Gel to bring to final weight. Mix the mixture with an electronic mortar and pestle for 3 min at a speed of about 1450 rpm. Process through an ointment mill once at the middle setting and once at the finest setting to reduce the particle size of the active ingredient and reduce air content of the preparation. Return the mixture to the electronic mortar and pestle and mix again for 1 min at a speed of about 1130 rpm. Package in a light-resistant calibrated dispenser.

2 ASSAY

Procedure

Solution A: 0.1% trifluoroacetic acid in acetonitrile

Solution B: 0.1% trifluoroacetic acid in water

Mobile phase: See Table 1.

Table 1

Standard solution: 0.05 mg/mL of USP Phenytoin RS in methanol

Sample solution

For Topical Gel 10 mg/g: Transfer 0.5 g of Topical Gel into a 50-mL centrifuge tube, add 19.5 mL of methanol, and vortex for 1 min.

Sonicate for 2 min and vortex for 1 min. Centrifuge the mixture for 10 min at 6000 rpm. Transfer 2 mL of the supernatant to a 10-mL volumetric flask and dilute with methanol to volume. Centrifuge for 10 min at 14,000 rpm.

For Topical Gel 50 mg/g: Transfer 0.5 g of Topical Gel into a 50-mL centrifuge tube, add 19.5 mL of methanol, and vortex for 1 min.

Sonicate for 2 min and vortex for 1 min. Centrifuge the mixture for 10 min at 6000 rpm. Transfer 0.4 mL of the supernatant to a 10-mL volumetric flask and dilute with methanol to volume. Centrifuge for 10 min at 14,000 rpm.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 2.1-mm × 5-cm; 1.7-μm packing L1

Temperatures

Autosampler: 8°

Column: 65°

Flow rate: 1 mL/min

Injection volume: 1 μL

System suitability

Sample: Standard solution

[Note - The retention time for phenytoin is about 1.3 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of phenytoin (C₁₅H₁₂N₂O₂) in the portion of Topical Gel taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of phenytoin 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 (mg/mL)

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

Acceptance criteria: 95.0%–105.0%

3 SPECIFIC TESTS

pH 〈791〉: 7.2–8.2

Viscosity - Rotational Methods 〈912〉: 500–3500 mPa · s

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in a tight, light-resistant calibrated dispenser. Store at controlled room temperature or in a refrigerator.

Beyond-Use Date: NMT 180 days after the date on which it was compounded when stored at controlled room temperature or in a refrigerator.

Labeling: Label it to indicate that it is for external use only and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Phenytoin RS