Vigabatrin 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

Vigabatrin Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of vigabatrin (C₆H₁₁NO₂).

2 IDENTIFICATION

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample: Grind an appropriate number of Tablets to prepare a 50-mg/mL solution of vigabatrin in water. Pass a portion of the solution through a suitable filter, and prepare a 2-mg/mL solution by mixing a suitable portion of the filtrate with acetone. Evaporate the solution to dryness in a stream of nitrogen. Prepare a potassium bromide pellet using a suitable amount of the residue. Alternatively, the Sample may be prepared by directly mixing an amount of finely ground Tablets (NLT 2) equivalent to about 3 mg of vigabatrin with about 200 mg of potassium bromide.

Acceptance criteria: The IR spectrum of the Sample is consistent with a similarly prepared pellet of USP Vigabatrin RS.

2.2 B. 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

3.1 Procedure

Buffer: 3.4 g/L of potassium phosphate, monobasic in water

Mobile phase: Acetonitrile, methanol, and Buffer (4:40:1000). Adjust with phosphoric acid to a pH of 2.8.

System suitability solution: 1.0 mg/mL of USP Vigabatrin RS and 12 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: 1.0 mg/mL of USP Vigabatrin RS in Mobile phase

Sample stock solution: Nominally 5.0 mg/mL of vigabatrin from Tablets (NLT 10) prepared as follows. Transfer a suitable number of Tablets to a suitable volumetric flask. Add Mobile phase to about 80% of the flask volume, and stir for 1 h to give a uniform dispersion of fine particulate. Dilute with Mobile phase to volume, and pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Sample solution: Nominally 1.0 mg/mL of vigabatrin from the Sample stock solution and Mobile phase. 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 210 nm
• Column: 4.6-mm × 25-cm; 10-µm packing L9
• Flow rate: 1.5 mL/min
• Injection volume: 50 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for vigabatrin related compound A and vigabatrin are about 0.7 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between vigabatrin related compound A and vigabatrin, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of vigabatrin (C₆H₁₁NO₂) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of vigabatrin from the Sample solution

rₛ = peak response of vigabatrin from the Standard solution

Cₛ = concentration of USP Vigabatrin RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of vigabatrin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 Dissolution 〈711〉

4.1.1 Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Mobile phase: Dissolve 6 g of sodium phosphate, monobasic in 800 mL of water. Add 100 mL of acetonitrile, and dilute with water to 1 L. Adjust with phosphoric acid to a pH of 2.3.

System suitability solution: 0.6 mg/mL of USP Vigabatrin RS and 6 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: (L/900) mg/mL of USP Vigabatrin RS in water

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 10-µm packing L9
• Flow rate: 1.0 mL/min
• Injection volume: 50 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for vigabatrin related compound A and vigabatrin are about 0.7 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between vigabatrin related compound A and vigabatrin, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (Q) of the labeled amount of vigabatrin (C₆H₁₁NO₂) dissolved:

Result = (rᵤ/rₛ) × (Cₛ/L) × V × 100

rᵤ = peak response of vigabatrin from the Sample solution

rₛ = peak response of vigabatrin from the Standard solution

Cₛ = concentration of USP Vigabatrin RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium

Tolerances: NLT 75% (Q) of the labeled amount of vigabatrin (C₆H₁₁NO₂) is dissolved in 30 min.

4.1.2 Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Mobile phase: Dissolve 6.9 g of sodium phosphate, monobasic in 800 mL of water. Add 100 mL of acetonitrile, and dilute with water to 1 L. Adjust with diluted phosphoric acid to a pH of 2.3.

System suitability solution: 0.6 mg/mL of USP Vigabatrin RS and 6 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase. Sonicate to dissolve if necessary.

Standard solution: (L/900) mg/mL of USP Vigabatrin RS in Medium, where L is the label claim, in mg/Tablet. Sonicate to dissolve.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 4 mL of the filtrate.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 10-µm packing L9
• Flow rate: 1 mL/min
• Injection volume: 50 µL
• Run time: NLT 1.7 times the retention time of vigabatrin

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for vigabatrin related compound A and vigabatrin are about 0.8 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between vigabatrin related compound A and vigabatrin, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of vigabatrin (C₆H₁₁NO₂) dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100

rᵤ = peak response of vigabatrin from the Sample solution

rₛ = peak response of vigabatrin from the Standard solution

Cₛ = concentration of USP Vigabatrin RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of vigabatrin (C₆H₁₁NO₂) is dissolved.

4.1.3 Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: Dissolve 6.0 g of sodium phosphate, monobasic, anhydrous in 800 mL of water.

Mobile phase: Acetonitrile, Buffer, and water (10:80:10). Adjust with phosphoric acid to a pH of 2.3.

System suitability solution: 0.6 mg/mL of USP Vigabatrin RS and 6 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: (L/900) mg/mL of USP Vigabatrin RS in Medium, where L is the label claim, in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first NLT 2 mL of the filtrate.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Columns
• Guard: 1.0-mm × 1-cm; 5-µm packing L3
• Analytical: 4.6-mm × 25-cm; 10-µm packing L9
• Flow rate: 1 mL/min
• Vigabatrin-Tablets-usp-ttt (1)
• Injection volume: 50 µL
• Run time: NLT 1.6 times the retention time of vigabatrin

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for vigabatrin related compound A and vigabatrin are about 0.7 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between vigabatrin related compound A and vigabatrin, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of vigabatrin (C₆H₁₁NO₂) dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100

rᵤ = peak response of vigabatrin from the Sample solution

rₛ = peak response of vigabatrin from the Standard solution

Cₛ = concentration of USP Vigabatrin RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of vigabatrin (C₆H₁₁NO₂) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

Buffer: 1.5 g/L of ammonium acetate in water

Mobile phase: Acetonitrile and Buffer (5:95)

System suitability solution: 0.1 mg/mL each of USP Vigabatrin RS, USP Vigabatrin Related Compound A RS, USP Vigabatrin Related Compound B RS, and USP Povidone RS in Mobile phase

Sensitivity solution: 0.01 mg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: 0.07 mg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Sample solution: Nominally 22 mg/mL of vigabatrin prepared as follows. Transfer a suitable amount of finely powdered Tablets (NLT 10) to a suitable volumetric flask. Add Mobile phase to 80% of the flask volume. Sonication may be used to aid in dissolution. Allow the resulting solution to cool to room temperature, and dilute with Mobile phase to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Flow rate: 1.0 mL/min
• Injection volume: 10 µL
• Run time: 12 times the retention time of the vigabatrin peak

System suitability

• Samples: System suitability solution, Sensitivity solution, and Standard solution
• [Note-See Table 1 for the relative retention times.]
• Suitability requirements
• Resolution: NLT 2.0 between vigabatrin related compound B and povidone, System suitability solution
• Relative standard deviation: NMT 5.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of vigabatrin related compound A from the Standard solution

Cₛ = concentration of USP Vigabatrin Related Compound A RS in the Standard solution

Cᵤ = nominal concentration of vigabatrin in the Sample solution

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

ᵃ RRF relative to vigabatrin related compound A.

ᵇ Included for peak identification only. Not to be included in Total impurities as it is controlled in the drug substance.

ᶜ Povidone is due to excipient. Included for identification only. Not to be included in Total impurities.

ᵈ 2-(2-Oxo-5-vinylpyrrolidin-1-yl)acetic acid.

ᵉ 4-Oxo-6-(2-oxo-5-vinylpyrrolidin-1-yl) hexanoic acid.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Povidone RS

USP Vigabatrin RS

USP Vigabatrin Related Compound A RS

5-Vinylpyrrolidin-2-one.

C₆H₉NO 111.14

USP Vigabatrin Related Compound B RS

(E)-2-(2-Aminoethyl)but-2-enoic acid hydrochloride.

C₆H₁₁NO₂ · HCl 165.62