Lamotrigine Orally Disintegrating 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

Lamotrigine Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of lamotrigine (C₉H₇Cl₂N₅).

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.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

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

Mobile phase: Methanol and Buffer (60:40)

Standard stock solution: 1.0 mg/mL of USP Lamotrigine RS in Mobile phase. Sonication may be used to aid dissolution.

Standard solution: 0.05 mg/mL of USP Lamotrigine RS from the Standard stock solution in Mobile phase

Sample stock solution: Nominally 2 mg/mL of lamotrigine prepared as follows. Finely powder Tablets (NLT 30) and transfer a portion of the powder equivalent to 500 mg of lamotrigine to a suitable volumetric flask. Dissolve the contents in about 55% of the flask volume of Mobile phase, sonicate for NLT 20 min with intermittent shaking, and dilute with Mobile phase to volume. Centrifuge a portion of the solution and use the supernatant. [Note—Centrifuging at a speed of NLT 3500 rpm for 10 min may be suitable.]

Sample solution: Nominally 0.05 mg/mL of lamotrigine prepared from the Sample stock solution in Mobile phase. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, and use a portion of the filtrate after discarding the first 4 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 10 μL

Run time: NLT 3.5 times the retention time of lamotrigine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamotrigine (C₉H₇Cl₂N₅) in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of lamotrigine from the Sample solution

r_S = peak response of lamotrigine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Disintegration 〈701〉: NMT 30 s

Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 75 rpm

Time: 15 min

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

Mobile phase: Acetonitrile and Buffer (25:75)

Standard stock solution: 1 mg/mL of USP Lamotrigine RS in methanol

Standard solution: (L/900) mg/mL of lamotrigine from Standard stock solution 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 0.22-μm pore size, and use a portion of the filtrate after discarding the first 4 mL of the solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 310 nm

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

Column temperature: 30°

Flow rate: 0.3 mL/min

Injection volume: 2.0 μL

Run time: NLT 1.5 times the retention time of lamotrigine

System suitability

Sample: Standard solution

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 lamotrigine (C₉H₇Cl₂N₅) dissolved:

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

r_U = peak response of lamotrigine from the Sample solution

r_S = peak response of lamotrigine from the Standard solution

C_S = concentration of USP Lamotrigine 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 lamotrigine (C₉H₇Cl₂N₅) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer: 2.7 g/L of monobasic potassium phosphate in water

Solution A: To 1500 mL of Buffer add 10 mL of triethylamine and adjust with phosphoric acid to a pH 2.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: 0.1 N hydrochloric acid VS

Standard stock solution: 100 μg/mL of USP Lamotrigine RS prepared as follows. Transfer a suitable portion of USP Lamotrigine RS into a suitable volumetric flask. Dissolve in 5% of the flask volume of methanol and dilute with Diluent to volume.

Standard solution: 2.5 μg/mL of USP Lamotrigine RS from the Standard stock solution in Diluent

Sensitivity solution: 0.5 μg/mL of USP Lamotrigine RS from the Standard stock solution in Diluent

Sample solution: Nominally 500 μg/mL of lamotrigine prepared as follows. Transfer a portion of the Tablet powder, equivalent to 50 mg of lamotrigine, to a suitable volumetric flask and dissolve the contents in 10% of the flask volume of methanol. Sonicate for NLT 10 min with intermittent shaking and dilute with Diluent to volume. Pass a portion of the solution through a suitabllter of 0.45-μm pore size, and use a portion of the filtrate after discarding the first 4 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

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

Column temperature: 35°

Flow rate: 1.0 mL/min

Injection volume: 10 μL

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Tailing factor: NMT 2.0 for lamotrigine, Standard solution

Relative standard deviation: NMT 5.0% for lamotrigine, Standard solution

Signal-to-noise ratio: NLT 10 for lamotrigine, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S)x(C_S/C_U) × (1/F) × 100

r_U = peak response of any individual impurity from the Sample solution

r_S = peak response of lamotrigine from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.10%.Table 2

Table 2

^a 3-Amino-6-(2,3-dichlorophenyl)-1,2,4-triazin-5(4H)-one.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Lamotrigine RS (USP 1-May-2021)