Topiramate Compounded 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

Topiramate Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of topiramate (C₁₂H₂₁NO₈S).

Prepare Topiramate Compounded Oral Suspension 20 mg/mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

^a Topiramate 200-mg tablets, Torrent Pharmaceuticals LTD, Kalamazoo, MI.

^b Perrigo, Minneapolis, MN.

If using tablets, comminute the tablets to a fine powder in a suitable mortar or other mechanical means, or add Topiramate powder to the mortar. Wet the powder with a small amount of Vehicle, and triturate to make a smooth paste. Add increasing volumes of the Vehicle to make the mortar contents pourable. Transfer the contents of the mortar, stepwise and quantitatively, to a calibrated container using the remainder of the Vehicle. Add sufficient Vehicle to bring to final volume. Shake to mix well.

2 ASSAY

PROCEDURE

Solution A: Weigh 6.24 g of monobasic sodium phosphate dihydrate, and transfer to a 1-L volumetric flask. Dissolve in 800 mL of water, add 30 mL of triethylamine, and adjust with phosphoric acid to a pH of 2.8. Dilute with water to volume, and mix thoroughly.

Solution B: Weigh 6.25 g of boric acid and 7.5 g of potassium chloride, and transfer to a 1-L volumetric flask. Dissolve in 900 mL of water, and adjust with potassium hydroxide to a pH of 7.8. Dilute with water to volume, and mix thoroughly.

Solution C: Transfer 50 mg of 9-fluorenylmethyl chloroformate to a 10-mL volumetric flask, and dilute with acetonitrile to volume. Store at 4", and protect from light.

Solution D: Transfer 100 mg of glycine to a 10-mL volumetric flask, and dilute with water to volume.

Mobile phase: Acetonitrile and Solution A (48:52). Filter, and degas.

Standard stock solution: 1 mg/mL of USP Topiramate RS in acetonitrile

Standard solution: Transfer 1 mL of Standard stock solution into a 10-mL volumetric flask, dilute with Solution B to volume, and mix well.

Sample solution: Shake thoroughly each bottle of Oral Suspension. Transfer 0.5 mL of the Oral Suspension into a 10-mL volumetric flask, add 2 mL of water and 5 mL of acetonitrile, and sonicate for 10 min. Dilute with water to volume, and mix well. Pass through a PVDF filter of 0.45-µm pore size, discarding the first 3 mL of filtrate. Mix 1 mL of the filtrate with 9 mL of Solution B. Transfer 100 µL of the resulting solution into a HPLC vial, add 50 µL of Solution C, and mix on a vortex mixer for 20 s. Incubate at 50 for 15 min. Immediately add 100 µL of Solution D to the vial to terminate the reaction. Mix on a vortex mixer for 10 s, and allow to stand for at least 1 min prior to analysis.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 264 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 52°

Flow rate: 1.0 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

(NOTE-The retention time for topiramate is about 8.8 min.]

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 topiramate (C₁₂H₂₁NO₈S) in the portion of Oral Suspension taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of topiramate from the Sample solution

r_s = peak response of topiramate from the Standard solution

C_s = concentration of topiramate in the Standard solution (mg/mL)

C_u = nominal concentration of topiramate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

PH (791): 3.9-4.9

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in tight, light-resistant containers. Store at 2°-8° or at controlled room temperature.

LABELING: Label it to indicate that it is to be well-shaken before use, and to state the Beyond-Use Date.

BEYOND-USE DATE: NMT 90 days after the date on which it was compounded when stored at 2°-8° or controlled room temperature.

USP REFERENCE STANDARDS (11)

LISP Togiramate RS