Topiramate Compounded Oral Suspension
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
).
795).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.
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.
, 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.
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
Mode:
LC
Detector:
UV 264 nm
Column:
4.6-mm × 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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of topiramate from the Sample solution |
| rS | = | = peak response of topiramate from the Standard solution |
| CS | = | = concentration of topiramate in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of topiramate in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
SPECIFIC TESTS
• pH 791:
3.9–4.9
791:
3.9–4.9
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Package in tight, light-resistant containers. Store at 2–8 or at controlled room temperature.
–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.
–8 or controlled room temperature.
• USP Reference Standards 11
11
USP Topiramate RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Jeanne H. Sun, Pharm.D.
Associate Scientific Liaison (301) 230-3361 |
(CMP2010) Compounding |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP38–NF33 Page 5624
Pharmacopeial Forum: Volume No. 39(4)