Lamotrigine Extended-Release Tablets
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This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb- lamotrigine-ert-20240628.
1 DEFINITION
Lamotrigine Extended-Release 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.
3 ASSAY
Procedure
Mobile phase: Acetonitrile, water, and tri
uoroacetic acid (25: 75: 0.05)
Diluent: Acetonitrile, methanol, and water (10:20:70)
Standard solution: 0.25 mg/mL of USP Lamotrigine RS in Diluent. Sonication may be used to aid dissolution.
Sample stock solution: 1.0–3.0 mg/mL of lamotrigine prepared as follows. Transfer Tablets (NLT 5) to a suitable volumetric flask containing 10% of the flask volume of acetonitrile. Allow the Tablets to disperse. Add 20% of the flask volume of methanol. Sonicate for 10 min. Add 30% of the flask volume of 0.1 N hydrochloric acid. Sonicate for 25 min or until a fine, even dispersion is obtained. Allow to cool to room temperature. Dilute with 0.1 N hydrochloric acid to volume. Pass a portion of the solution through a nylon filter of 0.45-μm pore size and use the filtrate.
Sample solution: Nominally 0.2–0.3 mg/mL of lamotrigine in 0.1 N hydrochloric acid from a suitable volume of Sample stock solution
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 270 nm
Column: 4.6-mm × 15-cm; 3-μm packing L1
Column temperature: 40°
Flow rate: 1 mL/min
Injection volume: 5 μL
Run time: NLT 8 times the retention time of lamotrigine
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 1.5%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5) in the portion of Tablets taken:
Result = (rU/rS)x(CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Lamotrigine RS in the Standard solution (mg/mL)
CU = nominal concentration of lamotrigine in the Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
4 PERFORMANCE TESTS
Change to read:
Dissolution 〈711〉
Test 1
Medium 1: 0.01 M hydrochloric acid; 700 mL
Medium 2: 7.8 g of tribasic sodium phosphate, and 22.5 g of sodium dodecyl sulfate in 1 L of water. This solution has a pH of about 12.
Apparatus 2: 50 rpm with sinkers (see Dissolution 〈711〉, Figure 2a)
Times
For Tablets labeled to contain 25 or 50 mg: 2, 7, and 15 h
For Tablets labeled to contain 100, 200, or 250 mg: 2, 5, and 12 h
For Tablets labeled to contain 300 mg: 2, 6, and 13 h
Procedure: Run the test with Medium 1 for 2 h. Add 200 mL of Medium 2, preheated at 37°. Within 5 min of the addition of Medium 2, withdraw the sample for the 2-h time point. Continue the testing by drawing samples at the time points specified in Table 1, Table 2, or Table 3, depending on the label claim.
Diluent: Medium 1 and Medium 2 (70:20)
Standard solution: (L/900) mg/mL of USP Lamotrigine RS in Diluent, where L is the label claim in mg/Tablet
Sample solution: Pass a suitable portion of the solution under test through a suitable filter of 0.45-μm pore size. Dilute with Diluent, if necessary.
Blank: Diluent
Instrumental conditions
Mode: UV
Analytical wavelength: 260 nm. [Note—Depending on the label claim, cells with suitable path lengths may be used.]
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount (Q) of lamotrigine (C9H7Cl2N5 ) dissolved at each time point i:
Result = (AU/AS)xCS × V × D × (1/L) × 100
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL)
V = volume of Medium, 900 mL
D = dilution factor, if needed
L = label claim (mg/Tablet)
Tolerances
For Tablets with 25- or 50-mg label claim: See Table 1.
For Tablets with 100-, 200-, or 250-mg label claim: See Table 2.
For Tablets with 300-mg label claim: See Table 3.
Table 1
| Time Point (i) | Time (h) | Amount Dissolved |
|---|---|---|
| 1 | 2 | NMT 10% |
| 2 | 7 | 35%–55% |
| 3 | 15 | NLT 80% |
Table 2
| Time Point (i) | Time (h) | Amount Dissolved | |
|---|---|---|---|
| 100 mg, 200 mg | 250 mg | ||
| 1 | 2 | NMT 10% | NMT 10% |
| 2 | 5 | 20%–45% | 20%–40% |
| 3 | 12 | NLT 80% | NLT 80% |
Table 3
| Time Point (i) | Time (h) | Amount Dissolved |
|---|---|---|
| 1 | 2 | NMT 10% |
| 2 | 6 | 25%–45% |
| 3 | 13 | NLT 80% |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Acid stage medium: 0.01 M hydrochloric acid; 700 mL
Buffer stage stock medium: 2.83 g of sodium phosphate monobasic, 1.72 g of sodium hydroxide, and 22.5 g of sodium dodecyl sulfate in 1L of water
Buffer stage medium: Acid stage medium and Buffer stage stock medium (70:20); 900 mL. Adjust with solution A (phosphoric acid in water
prepared by diluting 1 mL of phosphoric acid with water to 50 mL) or 0.1 N sodium hydroxide, if necessary, to a pH of 6.8. Record the
required volume of solution A or 0.1 N sodium hydroxide for adjustment of the pH to 6.8.
Apparatus 2: 50 rpm with stationary tablet bflasket. See Figures 2b and 2c in Dissolution 〈711〉.
Times
For Tablets labeled to contain 25 or 50 mg: 2 h in Acid stage medium; 4, 7, 9, and 15 h in Buffer stage medium
For Tablets labeled to contain 100, 200, or 300 mg: 2 h in Acid stage medium; 3, 5, 7, and 12 h in Buffer stage medium
[Note—The times in the Buffer stage medium include the time in the Acid stage medium.]
Procedure: Run the test with Acid stage medium for 2 h followed by collecting the Acid stage medium sample and replacing it with the same volume of Acid stage medium. Add 200 mL of Buffer stage stock medium to the above solution. If necessary, add either solution A or 0.1 N sodium hydroxide to the solution to reach a pH of 6.8. Continue the testing by drawing samples at the time points specified in Table 4 or Table 5, depending on the label claim. Replace each of the volumes withdrawn with an equal volume of Buffer stage medium.
Buffer: Dissolve 2.76 g of sodium phosphate monobasic in 1 L of water. Add 2 mL of triethylamine and adjust with solution A to a pH of 7.0.
Mobile phase: Methanol and Buffer (55:45)
Standard stock solution: 1.4 mg/mL of USP Lamotrigine RS in methanol
Acid stage standard solution: (L/900) mg/mL of USP Lamotrigine RS from Standard stock solution, in Acid stage medium, where L is the label claim in mg/Tablet
Buffer stage standard solution: (L/900) mg/mL of USP Lamotrigine RS from Standard stock solution, in Buffer stage medium, where L is the label claim in mg/Tablet
Acid stage sample solution: Withdraw a 10.0-mL aliquot, and pass a portion of the solution under test through a suitable filter of 0.45-μm
pore size. Replace the 10.0-mL aliquot withdrawn for analysis with a 10.0-mL aliquot of Acid stage medium.
Buffer stage sample solution: Withdraw a 10.0-mL aliquot, and pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Replace the 10.0-mL aliquot withdrawn for analysis with a 10.0-mL aliquot of Buffer stage medium.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 270 nm
Column: 4.6-mm × 15-cm; 5-μm packing L7
Flow rate: 1 mL/min
Injection volume
For 25-mg Tablets: 80 μL
For 50-mg Tablets: 40 μL
For 100-mg Tablets: 20 μL
For 200- or 300-mg Tablets: 10 μL
Run time: NLT 1.8 times the retention time of lamotrigine
System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage (Q ) of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved in the Acid stage medium:
Result = (rU/rS) × CS × VA × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Acid stage standard solution
CS = concentration of USP Lamotrigine RS in the Acid stage standard solution (mg/mL)
VA = volume of the Acid stage medium, 700 mL
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i) during the
buffer stage:
Result = (rU/rS)xCS
rU = peak response from the Buffer stage sample solution at time point i
rS = peak response from the Buffer stage standard solution
CS = concentration of USP Lamotrigine RS in the Buffer stage standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i) during the buffer stage:
Result1 = [C1 × VB × (1/L) × 100] + (QA × VS/VA)
Result2 = {[(C2 × VB ) + (C1 × VS)] × (1/L) × 100} + (QA × VS/VA)
Result3 = ({(C3 × VB ) + [(C2 + C1) × VS ]} × (1/L) × 100) + (QA × VS/VA)
Result4 = ({(C4 × VB ) + [(C3 + C2 + C1 ) × VS ]} × (1/L) × 100) + (QA × VS/VA)
Ci = concentration of lamotrigine in the Buffer stage sample solution withdrawn at time point i (mg/mL)
VB = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
QA = the percentage of the labeled amount of lamotrigine dissolved in the Acid stage medium
VS = volume of the sample solution withdrawn at each time point (i) during the acid stage or buffer stage (mL)
VA = volume of the Acid stage medium, 700 mL
Tolerances
For Tablets labeled to contain 25 or 50 mg: See Table 4.
For Tablets labeled to contain 100, 200, or 300 mg: See Table 5.
Table 4
Table 4
| Time Point (i) | Time (h) | Amount Dissolved |
|---|---|---|
| 1 | 2 | NMT 10% |
| 2 | 4 | 5%–25% |
| 3 | 7 | 30%–50% |
| 4 | 9 | 50%–70% |
| 5 | 15 | NLT 80% |
4.1 Table 5
| Time Point (i) | Time (h) | Amount Dissolved |
|---|---|---|
| 1 | 2 | NMT 10% |
| 2 | 3 | 5%–20% |
| 3 | 5 | 25%–50% |
| 4 | 7 | 50%–70% |
| 5 | 12 | NLT 80% |
Table 6
| Time Point (i) | Time (h) | Amount Dissolved |
|---|---|---|
| 1 | 2 | NMT 10% |
| 2 | 3 | 5%–20% |
| 3 | 5 | 25%–50% |
| 4 | 7 | 50%–70% |
| 5 | 12 | NLT 80% |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2.
Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Acid stage medium: 0.01 M hydrochloric acid; 700 mL
Buffer stage stock medium: 7.8 g of sodium phosphate tribasic and 22.5 g of sodium dodecyl sulfate in 1 L of water
Buffer stage medium: Acid stage medium and Buffer stage stock medium (70:20); 900 mL. Adjust with 2 N hydrochloric acid TS or 2 N sodium hydroxide TS, if necessary, to a pH of 6.8.
Apparatus 2: 50 rpm with stationary tablet bflasket. See Figures 2b and 2c in Dissolution 〈711〉.
Times
For Tablets labeled to contain 25, 50, 100, or 200 mg: 2 h in Acid stage medium; 4, 7, and 14 h in Buffer stage medium
[Note—The times in the Buffer stage medium include the time in the Acid stage medium.]
Procedure: Run the test with Acid stage medium for 2 h followed by collecting the Acid stage medium sample and replacing it with the same volume of Acid stage medium. Add 200 mL of Buffer stage stock medium to the above solution. Continue the testing by drawing samples at the time points specified in Table 6. Replace each of the volumes withdrawn with an equal volume of the Buffer stage medium.
Buffer: Dissolve 2.72 g of potassium phosphate monobasic in 1 L of water and adjust with dilute phosphoric acid to a pH of 3.7.
Mobile phase: Methanol, acetonitrile, and Buffer (50:15:35)
Standard stock solution: 0.6 mg/mL of USP Lamotrigine RS in methanol. Sonicate to dissolve as needed.
Acid stage standard solution: 0.036 mg/mL of USP Lamotrigine RS from Standard stock solution, in Acid stage medium
Buffer stage standard solution: (L/900) mg/mL of USP Lamotrigine RS from Standard stock solution, in Buffer stage medium, where L is the label claim in mg/Tablet
Acid stage sample solution: Withdraw a 10.0-mL aliquot and pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding the first 5 mL of the filtrate. Replace the 10.0-mL aliquot withdrawn for analysis with a 10.0-mL aliquot of Acid stage medium.
Buffer stage sample solution: Withdraw a 10.0-mL aliquot and pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Replace the 10.0-mL aliquot withdrawn for analysis with a 10.0-mL aliquot of Buffer stage medium.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 270 nm
Column: 4.6-mm × 25-cm; 5-μm packing L1
Column temperature: 35°
Flow rate: 1 mL/min
Injection volume: 10 μL
Run time: NLT 1.7 times the retention time of lamotrigine
System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage (QA) of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved in the Acid stage medium:
Result = (rU/rS) × CS × VA × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Acid stage standard solution
CS = concentration of USP Lamotrigine RS in the Acid stage standard solution (mg/mL)
VA = volume of the Acid stage medium, 700 mL
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i) during the buffer stage:
Result = (rU/rS)xCS
rU = peak response from the Buffer stage sample solution at time point i
rS = peak response from the Buffer stage standard solution
CS = concentration of USP Lamotrigine RS in the Buffer stage standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i) during the buffer stage:
Result1 = [C1 × VB × (1/L) × 100] + (QA × VS/VA)
Result2 = {[(C2 × VB ) + (C1 × VS)] × (1/L) × 100} + (QA × VS/VA)
Result3 = ({(C3 × VB ) + [(C2 + C1) × VS ]} × (1/L) × 100) + (QA × VS/VA)
CI = concentration of lamotrigine in the Buffer stage sample solution withdrawn at time point i (mg/mL)
VB = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
Q = the percentage of the labeled amount of lamotrigine dissolved in the Acid stage medium
VS = volume of the sample solution withdrawn at each time point (i) during the acid stage or buffer stage (mL)
VA = volume of the Acid stage medium, 700 mL
Tolerances
For Tablets labeled to contain 25, 50, 100, or 200 mg: See Table 6.
Table 6
| Time Point (i) | Time (h) | Amount Dissolved (%) |
|---|---|---|
| 1 | 2 | NMT 10 |
| 2 | 4 | NMT 25 |
| 3 | 7 | 36–61 |
| 4 | 14 | NLT 85 |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2.
Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Acid stage medium: 0.01 M hydrochloric acid; 700 mL
Buffer stage stock medium: 7.8 g of sodium phosphate tribasic and 22.5 g of sodium dodecyl sulfate in 1 L of water
Buffer stage medium: Acid stage medium and Buffer stage stock medium (70:20); 900 mL
Apparatus 2: 50 rpm with sinkers
Times
For Tablets labeled to contain 25, 50, 100, 200, or 300 mg: 2 h in Acid stage medium; 9 and 17 h in Buffer stage medium
[Note—The times in the Buffer stage medium include the time in the Acid stage medium.]
Procedure: Run the test with Acid stage medium for 2 h followed by collecting the Acid stage medium sample and replacing it with the same volume of Acid stage medium. Add 200 mL of Buffer stage stock medium to the above solution. Continue the testing by drawing samples at the time points specified in Table 7. Replace each of the volumes withdrawn with an equal volume of the Buffer stage medium.
Buffer: Dissolve 4.1 g of potassium phosphate monobasic in 900 mL of water and adjust with dilute phosphoric acid to a pH of 2.0, and then dilute with water to 1 L. Add 1.25 g of sodium 1-hexanesulfonate to the solution and mix.
Mobile phase: Acetonitrile and Buffer (25:75)
Acid stage standard stock solution 1: 0.07 mg/mL of USP Lamotrigine RS prepared as follows. Transfer an appropriate amount of USP
Lamotrigine RS to a suitable volumetric flask and add 20% of the flask volume of methanol. Sonicate to dissolve and dilute with Acid stage medium to volume. Further dilute this solution with Acid stage medium to obtain a final concentration of 0.07 mg/mL.
Acid stage standard stock solution 2: 0.14 mg/mL of USP Lamotrigine RS prepared as follows. Transfer an appropriate amount of USP
Lamotrigine RS to a suitable volumetric flask and add 20% of the flask volume of methanol. Sonicate to dissolve and dilute with Acid stage medium to volume. Further dilute this solution with Acid stage medium to obtain final concentration of 0.14 mg/mL.
Acid stage standard solution: 0.1 × (L/700) mg/mL of USP Lamotrigine RS either from Acid stage standard stock solution 1 for Tablets labeled to contain 25, 50, 100, and 200 mg, or from Acid stage standard stock solution 2 for Tablets labeled to contain 300 mg, in Acid stage medium, where L is the label claim in mg/Tablet. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of the filtrate.
Buffer stage standard stock solution 1: 0.55 mg/mL of USP Lamotrigine RS prepared as follows. Transfer an appropriate amount of USP Lamotrigine RS to a suitable volumetric flask and add 10% of the flask volume of methanol. Sonicate to dissolve and dilute with Buffer stage medium to volume.
Buffer stage standard stock solution 2: 1.1 mg/mL of USP Lamotrigine RS prepared as follows. Transfer an appropriate amount of USP Lamotrigine RS to a suitable volumetric flask and add 20% of the flask volume of methanol. Sonicate to dissolve and dilute with Buffer stage medium to volume.
Buffer stage standard solution: (L/900) mg/mL of USP Lamotrigine RS either from Buffer stage standard stock solution 1 for Tablets labeled to contain 25, 50, 100, and 200 mg, or from Buffer stage standard stock solution 2 for Tablets labeled to contain 300 mg, in Buffer stage medium, where L is the label claim in mg/Tablet. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of the filtrate.
Acid stage sample solution: Withdraw a 10.0-mL aliquot and pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of the filtrate. Replace the 10.0-mL aliquot withdrawn for analysis with a 10.0-mL aliquot of Acid stage medium. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of the filtrate.
Buffer stage sample solution: Withdraw a 10.0-mL aliquot and pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Replace the 10.0-mL aliquot withdrawn for analysis with a 10.0-mL aliquot of Buffer stage medium. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of the filtrate.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 270 nm
Column: 4.6-mm × 25-cm; 5-μm packing L7
Column temperature: 60°
Flow rate: 1 mL/min
Injection volume: 10 μL
Run time: NLT 2 times the retention time of lamotrigine
System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage (QA) of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved in the Acid stage medium:
Result = (rU/rS) × CS × VA × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Acid stage standard solution
CS = concentration of USP Lamotrigine RS in the Acid stage standard solution (mg/mL)
VA = volume of the Acid stage medium, 700 mL
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i) during the buffer stage:
Result = (rU/rS)xCS
rU = peak response from the Buffer stage sample solution at time point i
rS = peak response from the Buffer stage standard solution
CS = concentration of USP Lamotrigine RS in the Buffer stage standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i) during the buffer stage:
Result1 = [C1 × VB × (1/L) × 100] + (QA × VS/VA)
Result2 = {[(C2 × VB ) + (C1 × VS)] × (1/L) × 100} + (QA × VS/VA)
Ci = concentration of lamotrigine in the Buffer stage sample solution withdrawn at time point i (mg/mL)
V = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
QA = the percentage of the labeled amount of lamotrigine dissolved in the Acid stage medium
VS = volume of the sample solution withdrawn at each time point (i) during the acid stage or buffer stage (mL)
VB = volume of the Acid stage medium, 700 mL
Tolerances
For Tablets labeled to contain 25, 50, 100, 200, or 300 mg: See Table 7.
Table 7
| Time Point (i) | Time (h) | Amount Dissolved (%) |
|---|---|---|
| 1 | 2 | NMT 10 |
| 2 | 9 | 35–55 |
| 3 | 17 | NLT 80 |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2.
Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Acid stage medium: 0.01 M hydrochloric acid; 710 mL
Buffer stage stock medium: 3.36 g of anhydrous tribasic sodium phosphate and 22.5 g of sodium dodecyl sulfate in 1 L of water
Buffer stage medium: Acid stage medium and Buffer stage stock medium (70:20); 900 mL. Adjust with hydrochloric acid or 5 N sodium hydroxide TS, if necessary, to a pH of 6.8. Apparatus 2: 50 rpm with sinkers Times For Tablets labeled to contain 25, 50, 100, or 200 mg: 2 h in Acid stage medium; 4, 7, and 17 h in Buffer stage medium [Note—The times in the Buffer stage medium include the time in Acid stage medium.]
Procedure: Run the test with Acid stage medium for 2 h followed by collecting the Acid stage medium sample. Add 200 mL of Buffer stage stock medium to this solution. Continue the testing by drawing samples at the time points specified in Table 8.
Buffer: Dissolve 3.45 g of monobasic sodium phosphate in 1 L of water, and adjust with phosphoric acid to a pH of 3.3. To this solution, add 5.77 g of sodium dodecyl sulfate, and mix well.
Mobile phase: Acetonitrile and Buffer (45:55)
Standard solution: 0.22 mg/mL of USP Lamotrigine RS in Mobile phase. Sonicate to dissolve as needed.
Acid stage sample solution: Withdraw a 10.0-mL aliquot, and pass a portion of the solution under test through a suitable full flow filter of 10-μm pore size.
Buffer stage sample solution: Withdraw a 2.5-mL aliquot, and pass a portion of the solution under test through a suitable full flow filter of 10-μm pore size.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 266 nm
Column: 4.6-mm × 5-cm; 3.5-μm packing L1
Column temperature: 30°
Flow rate: 1 mL/min
Injection volume: 10 μL
Run time: NLT 1.6 times the retention time of lamotrigine
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 1.5
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage (QA) of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved in the Acid stage medium:
Result = (rU/rS) × CS × VA × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Standard solution
CS = concentration of USP Lamotrigine RS in the Standard solution (mg/mL)
VA = volume of the Acid stage medium, 710 mL
L = label claim (mg/Tablet)
Calculate the concentration (CI) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i) during the buffer stage:
Result = (rU/rS)xCS
rU = peak response from the Buffer stage sample solution at time point i
rS = peak response from the Standard solution
CS = concentration of USP Lamotrigine RS in the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i) during the buffer stage:
Result1 = [C1 × VB × (1/L) × 100] + (QA × VS/VA)
Result2 = {[C2 × (VB - VS) + (C1 × VS)] × (1/L) × 100} + (QA × VS/VA)
Result3 = {[C3 × (VB - 2VS) + [(C2 +C1) × VS]} × (1/L) × 100) + (QA × VS/VA)
Ci = concentration of lamotrigine in the Buffer stage sample solution withdrawn at time point i (mg/mL)
VB = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
Q = the percentage of the labeled amount of lamotrigine dissolved in the Acid stage medium
VS = volume of the Sample solution withdrawn at each time point (i), 10 mL for acid stage or 2.5 mL for buffer stage
VA = volume of the Acid stage medium, 710 mL
Tolerances
For Tablets labeled to contain 25, 50, 100, or 200 mg: See Table 8.
Table 8
| Time Point (i) | Time (h) | Amount Dissolved | |
|---|---|---|---|
| 25, 50, and 200 mg/Tablet (%) | 100 mg/Tablet (%) | ||
| 1 | 2 | NMT 10 | NMT 10 |
| 2 | 4 | 10–30 | 10–30 |
| 3 | 7 | 35–60 | 40–65 |
| 4 | 17 | NLT 80 | NLT 80 |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.
Acid stage medium: 0.01 N hydrochloric acid TS; 700 mL, degas by helium sparging before use
Buffer stage stock medium: 7.8 g of sodium phosphate tribasic in 1 L of water, add 2 mL of sodium hydroxide TS and degas by helium sparging, then add 22.5 g of sodium dodecyl sulfate and mix well. Degas by warming the solution to NMT 50° and bring back to 37° before use.
Buffer stage medium: Acid stage medium and Buffer stage stock medium (70:20), pH 6.8; 900 mL. Adjust with 1 N hydrochloric acid VS or sodium hydroxide TS, if necessary.
Apparatus 1: 75 rpm for Tablets labeled to contain 25, 50, 100, 200, or 300 mg
Apparatus 2: 50 rpm for Tablets labeled to contain 250 mg
Times: 2 h in Acid stage medium; see Table 9 for times in Buffer stage medium. The times in the Buffer stage medium include the time in
Acid stage medium.
Procedure: Run the test with Acid stage medium for 2 h followed by collecting the Acid stage medium sample and replacing it with the same volume of Acid stage medium. Add 200 mL of Buffer stage stock medium to the above solution. Continue the testing by drawing samples at the time points specified in Table 9 without replacing the withdrawn volume.
Buffer: 3.85 g/L of ammonium acetate in water, adjust with acetic acid to a pH of 5.60 ± 0.05
Mobile phase: Acetonitrile and Buffer (32:68)
Standard stock solution: 2.0 mg/mL of USP Lamotrigine RS prepared as follows. Transfer an appropriate amount of USP Lamotrigine RS to a suitable volumetric flask and add 50% of the flask volume of methanol. Sonicate with occasional swirling for 5 min or until the Reference Standard is completely dissolved. Dilute with Buffer stage medium to volume.
Standard solution: 0.16 mg/mL of USP Lamotrigine RS from Standard stock solution in Buffer stage medium
Acid stage sample solution: Withdraw a suitable volume of the solution under test and replace the withdrawn aliquot with the same volume of Acid stage medium. Pass a portion of the withdrawn solution through a filter of suitable pore size. Discard the first few milliliters of the filtrate.
Buffer stage sample solution: Withdraw a suitable volume of the solution under test and pass a portion of the withdrawn solution through a filter of suitable pore size. Discard the first few milliliters of the
filtrate.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 306 nm
Column: 4.6-mm × 15-cm; 5-μm packing L7
Column temperature: 30°
Flow rate: 1 mL/min
Injection volume: 10 μL
Run time: NLT 1.4 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, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage (Q ) of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved in the Acid stage medium:
Result = (rU/rS) × CS × VA × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Standard solution
CS = concentration of USP Lamotrigine RS in the Standard solution (mg/mL)
VA = volume of the Acid stage medium, 700 mL
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i) during the buffer stage:
Result = (rU/rS)xCS
rU = peak response from the Buffer stage sample solution at time point i
rS = peak response from the Standard solution
CS = concentration of USP Lamotrigine RS in the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i) during the buffer stage:
Result2 = [C2 × VB × (1/L) × 100] + (QA × VS/VA)
Result3 = {[C3 × (VB - VS) + (C2 × VS)] × (1/L) × 100} + (QA × VS/VA)
Result4 = {[C4 × (VB - 2VS) + [(C3 +C2) × VS]} × (1/L) × 100) + (QA × VS/VA)
Ci = concentration of lamotrigine in the Buffer stage sample solution withdrawn at time point i (mg/mL)
VB = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
Q = percentage of the labeled amount of lamotrigine dissolved in the Acid stage medium
VS = volume of the Sample solution withdrawn at each time point (i)
VA = volume of the Acid stage medium, 700 mL
Tolerances: See Table 9.
Table 9
| Time Point (i) | Time (h) | Amount Dissolved | |||||
|---|---|---|---|---|---|---|---|
| 25 mg/Tablet (%) | 50 mg/Tablet (%) | 100 mg/Tablet (%) | 200 mg/Tablet (%) | 250 mg/Tablet (%) | 300 mg/Tablet (%) | ||
| 1 | 2 | NMT 10 | NMT 10 | NMT 10 | NMT 10 | NMT 10 | NMT 10 |
| 2 | 4 | 10–30 | 10–30 | 10–30 | 10–30 | 8–25 | 10–28 |
| 3 | 7 | – | – | 53–73 | – | – | – |
| 8 | 50–70 | – | – | 50–70 | – | 50–70 | |
| 9 | – | 45–65 | – | – | 55–75 | – | |
| 4 | 10 | – | – | NLT 80 | – | – | – |
| 11 | – | – | – | – | – | NLT 80 | |
| 12 | NLT 80 | – | – | NLT 80 | – | – | |
| 14 | – | NLT 80 | – | – | – | – | |
| 15 | – | – | – | – | NLT 85 | – | |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2.
Test 9: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 9.
Acid stage
Acid stage medium: 0.01 N hydrochloric acid; 700 mL
Apparatus 2: 50 rpm, with stationary bflasket. See 〈711〉, Figures 2b and 2c.
Time: 2 h
Buffer: 2 mL/L of triethylamine in water. Adjust with phosphoric acid to a pH of 2.5.
Mobile phase: Acetonitrile and Buffer (30:70)
Acid stage standard stock solution: 0.36 mg/mL of USP Lamotrigine RS in methanol. Sonicate to dissolve, if necessary.
Acid stage standard solution: (L/7000) mg/mL of USP Lamotrigine RS from Acid stage standard stock solution in Acid stage medium, where L is the label claim in mg/Tablet.
Acid stage sample solution: At the end of the 2 h Acid stage, withdraw 10 mL of the solution under test and replace the withdrawn aliquot with the same volume of Acid stage medium. Pass a portion of the solution withdrawn through a suitable filter of 0.45-μm pore size, discarding the first 3 mL of filtrate.
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: 50°
Flow rate: 0.7 mL/min
Injection volume: 20 μL
Run time: NLT 3 times the retention time of lamotrigine
System suitability
Sample: Acid stage Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Acid stage standard solution and Acid stage sample solution
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved in the Acid stage:
Result = (rU/rS) × CS × VA × (1/L) × 100
rU = peak response of lamotrigine from the Acid stage sample solution
rS = peak response of lamotrigine from the Acid stage standard solution
CS = concentration of USP Lamotrigine RS in the Acid stage standard solution (mg/mL)
VA = volume of the Acid stage medium, 700 mL
L = label claim (mg/Tablet)
Tolerances: NMT 10%. The percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the time specified conforms to
Dissolution 〈711〉, Acceptance Table 3.
Buffer stage
Buffer stage stock medium: 7.8 g/L of sodium phosphate tribasic and 22.3 g/L of sodium dodecyl sulfate in water prepared as follows.
Dissolve 7.8 g of sodium phosphate tribasic in 1000 mL of water. Add 22.3 g of sodium dodecyl sulfate and mix well.
Buffer stage medium: Acid stage medium and Buffer stage stock medium (70:20); 900 mL.
Apparatus 2: 50 rpm, with stationary bflasket. See 〈711〉, Figures 2b and 2c.
Times:
For Tablets labeled to contain 25 and 50 mg: 2, 7, and 15 h
For Tablets labeled to contain 100 and 200 mg
(RB 1-Jul-2024) : 1, 4, and 11 h
For Tablets labeled to contain 250 and 300 mg: 1, 5, and 11 h (RB 1-Jul-2024)
Buffer: 2 mL/L of triethylamine in water. Adjust with phosphoric acid to a pH of 2.5.
Mobile phase: Acetonitrile and Buffer (35:65)
Buffer stage standard stock solution: 1.11 mg/mL of USP Lamotrigine RS in methanol. Sonicate to dissolve, if necessary.
Buffer stage standard solution: (L/900) mg/mL of USP Lamotrigine RS from Buffer stage standard stock solution in Buffer stage medium, where L is the label claim in mg/Tablet.
Buffer stage sample solution: After the 2 h in the Acid stage, add 200 mL of Buffer stage stock medium to the vessel containing Acid stage medium. At the times specified, withdraw 10 mL of the solution under test and replace the withdrawn aliquot with the same volume of
Buffer stage medium. Pass a portion of the solution withdrawn through a suitable filter of 0.45-μm pore size, discarding the first 5 mL of filtrate.
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: 50°
Flow rate: 1 mL/min
Injection volume: 5 μL
Run time: NLT 3 times the retention time of lamotrigine
System suitability
Sample: Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Buffer stage standard solution and Buffer stage sample solution
Calculate the concentration (Ci) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i) in the
Buffer stage:
Result = (rU/rS)xCS
rU= peak response of lamotrigine from the Buffer stage sample solution
rS = peak response of lamotrigine from the Buffer stage standard solution
CS = concentration of USP Lamotrigine RS in the Buffer stage standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i) in the Buffer stage:
Result1 = C1 × V × (1/L) × 100
Result2 = [(C2 × V) + (C1 × VS )] × (1/L) × 100
Result3 = {(C3 × V) + [(C2 + C1 ) × V=VS ]} × (1/L) × 100
Ci = concentration of lamotrigine in the portion of sample withdrawn at time point i (mg/mL)
V = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
VS = volume of the Buffer stage sample solution withdrawn at each time point and replaced with Buffer stage medium, 10 mL
Tolerances: See Table 10.
Table 10
| For Tablets Labeled to Contain 25 and 50 mg of Lamotrigine | For Tablets Labeled to Contain 100 mg of Lamotrigine | For Tablets Labeled to Contain 200 mg of Lamotrigine | For Tablets Labeled to Contain 250 mg of Lamotrigine | For Tablets Labeled to Contain 300 mg of Lamotrigine | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Time Point (i) | Time (h) | Amount Dissolved (%) | Time (h) | Amount Dissolved (%) | Time (h) | Amount Dissolved (%) | Time (h) | Amount Dissolved (%) | Time (h) | Amount Dissolved (%) |
| 1 | 2 | 5–25 | 1 | NMT 20 | 1 | NMT 20 | 1 | NMT 20 | 1 | NMT 20 |
| 2 | 7 | 45–65 | 4 | 30–50 | 4 | 38–58 | 5 | 46–66 | 5 | 42–62 |
| 3 | 15 | NLT 80 | 11 | NLT 80 | 11 | NLT 80 | 11 | NLT 80 | 11 | NLT 80 |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2.
Test 10: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 10.
Acid stage medium: 0.01 N hydrochloric acid; 700 mL
Buffer stage medium: To 700 mL of Acid stage medium, add 200 mL of a pre-warmed solution containing 7.8 g of sodium phosphate,
tribasic and 22.5 g of sodium dodecyl sulfate in 1 L of water; 900 mL.
Apparatus 2: 50 rpm with sinkers (see Dissolution 〈711〉, Figure 2a)
Times
For Tablets labeled to contain 25 and 50 mg: 2 h in Acid stage medium; 7 and 15 h in Buffer stage medium. The times in the Buffer stage medium include the time in the Acid stage medium.
For Tablets labeled to contain 100, 200, and 250 mg: 2 h in Acid stage medium; 5 and 14 h in Buffer stage medium. The times in the Buffer stage medium include the time in the Acid stage medium.
For Tablets labeled to contain 300 mg: 2 h in Acid stage medium; 6 and 13 h in Buffer stage medium. The times in the Buffer stage medium include the time in the Acid stage medium.
Buffer: Dissolve 6.8 g of potassium phosphate monobasic in 1 L of water.
Mobile phase: Methanol and Buffer (60:40)
Standard stock solution
For Tablets labeled to contain 25 mg: 0.28 mg/mL of USP Lamotrigine RS prepared as follows. Transfer a quantity of USP Lamotrigine RS to an appropriate volumetric flask and add 7.5% of the flask volume of methanol. Sonicate to dissolve, if necessary. Dilute with Buffer stage medium to volume.
For Tablets labeled to contain 50 mg: 0.56 mg/mL of USP Lamotrigine RS prepared as follows. Transfer a quantity of USP Lamotrigine RS to an appropriate volumetric flask and add 15% of the flask volume of methanol. Sonicate to dissolve, if necessary. Dilute with Buffer stage medium to volume.
Standard solution
For Tablets labeled to contain 25 mg: 0.028 mg/mL of USP Lamotrigine RS from Standard stock solution in Buffer stage medium
For Tablets labeled to contain 50 mg: 0.056 mg/mL of USP Lamotrigine RS from Standard stock solution in Buffer stage medium
For Tablets labeled to contain 100, 200, 250, and 300 mg: (L/900) mg/mL of USP Lamotrigine RS, where L is the label claim in
mg/Tablet, prepared as follows. Transfer a quantity of USP Lamotrigine RS to an appropriate volumetric flask and add 7.5% of the flask volume of methanol. Sonicate to dissolve, if necessary. Dilute with Buffer stage medium to volume.
Sample solution: At the times specified, pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Replace the portion removed with an equal volume of fresh
Acid stage medium or Buffer stage medium at 37°.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 310 nm
Column: 4.6-mm × 15-cm; 5-μm packing L1
Column temperature: 30°
Flow rate: 1 mL/min
Injection volume: 10 μL
Run time: NLT 2 times the retention time of lamotrigine
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 1.5%
Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (Ci) of lamotrigine (C9H7Cl2N5 ) in the sample withdrawn from the vessel at each time point (i):
Result = (rU/rS)xCS
rU = peak response of lamotrigine from the Sample solution
rS = peak response of lamotrigine from the Standard solution
CS = concentration of USP Lamotrigine RS in the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i):
Result1 = C1 × VA × (1/L) × 100
Result2 = [(C2 × VB) + (C1 × VS )] × (1/L) × 100
Result3 = {(C3 × VB) + [(C2 + C1 ) × VS ]} × (1/L) × 100
Ci = concentration of lamotrigine in the portion of sample withdrawn at time point i (mg/mL)
VA = volume of the Acid stage medium, 700 mL
VB = volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
V = volume of the Sample solution withdrawn at each time point and replaced with Acid stage medium or Buffer stage medium (mL)
Tolerances: See Table 11, Table 12, and Table 13.
Table 11
| Time Point (i) | Time (h) | Amount Dissolved (for Tablets labeled to contain 25 mg of lamotrigine) (%) | Amount Dissolved (for Tablets labeled to contain 50 mg of lamotrigine) (%) |
|---|---|---|---|
| 1 | 2 | NMT 10 | NMT 10 |
| 2 | 7 | 35–55 | 31–51 |
| 3 | 15 | NLT 80 | NLT 80 |
Table 12
| Time Point (i) | Time (h) | Amount Dissolved (for Tablets labeled to contain 100, 200, and 250 mg of lamotrigine) (%) |
|---|---|---|
| 1 | 2 | NMT 10 |
| 2 | 5 | 20–40 |
| 3 | 14 | NLT 80 |
Table 13
| Time Point (i) | Time (h) | Amount Dissolved (for Tablets labeled to contain 300 mg of lamotrigine) (%) |
|---|---|---|
| 1 | 2 | NMT 10 |
| 2 | 6 | 25–45 |
| 3 | 13 | NLT 80 |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2.
Test 11: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 11.
Acid stage medium: 0.01 N hydrochloric acid, deaerated, if necessary; 700 mL
Buffer stage medium: To 700 mL of Acid stage medium, add 200 mL of a pre-warmed solution containing 2.9 g of sodium phosphate, dibasic, anhydrous, 22.5 g of sodium dodecyl sulfate, and 4 mL of 5 N sodium hydroxide solution in 1 L of water. Adjust with 5 N sodium hydroxide or 5 N hydrochloric acid to a pH of 6.8; 900 mL.
Apparatus 2: 50 rpm with suitable sinkers
Times: 2 h in Acid stage medium; 6, 10, and 16 h in Buffer stage medium. The times in the Buffer stage medium include the time in the Acid stage medium.
Acid stage standard solution
For Tablets labeled to contain 25 and 50 mg: (L/2500) mg/mL of USP Lamotrigine RS in Acid stage medium, where L is the label claim in mg/Tablet. Sonicate to dissolve, if necessary.
For Tablets labeled to contain 100, 200, 250, and 300 mg: (L/2000) mg/mL of USP Lamotrigine RS in Acid stage medium, where L is the label claim in mg/Tablet. Sonicate to dissolve, if necessary.
Buffer stage standard solution
For Tablets labeled to contain 25 and 50 mg: (L/950) mg/mL of USP Lamotrigine RS in Buffer stage medium, where L is the label claim in mg/Tablet. Sonicate to dissolve, if necessary.
For Tablets labeled to contain 100, 200, 250, and 300 mg: (L/900) mg/mL of USP Lamotrigine RS in Buffer stage medium, where L is the label claim in mg/Tablet. Sonicate to dissolve, if necessary.
Acid stage sample solution: Pass through a suitable filter of 2.7-μm or 10-μm pore size.
Buffer stage sample solution: Pass through a suitable filter of 2.7-μm or 10-μm pore size.
Instrumental conditions
(See Ultraviolet-Visible Spectroscopy 〈857〉.)
Mode: UV-Vis
Analytical wavelength: 270 nm
Cell
For Tablets labeled to contain 25 and 50 mg: 0.5-cm flow cell
For Tablets labeled to contain 100, 200, 250, and 300 mg: 0.1-cm flow cell
Blank: Acid stage medium or Buffer stage medium
Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at each time point (i):
Result = (AU/AS)xCS × VA × (1/L) × 100
AU = absorbance of the Acid stage sample solution or Buffer stage sample solution
AS = absorbance of the Acid stage standard solution or Buffer stage standard solution
CS = concentration of USP Lamotrigine RS in the Acid stage standard solution or Buffer stage standard solution (mg/mL)
VA = volume of the Acid stage medium, 700 mL or volume of the Buffer stage medium, 900 mL
L = label claim (mg/Tablet)
Tolerances: See Table 14.
Table 14
| Time Point (i) | Time (h) | Amount Dissolved (for Tablets labeled to contain 25 and 200 mg of lamotrigine) (%) | Amount Dissolved (for Tablets labeled to contain 50 mg of lamotrigine) (%) | Amount Dissolved (for Tablets labeled to contain 100 mg of lamotrigine) (%) | Amount Dissolved (for Tablets labeled to contain 250 mg of lamotrigine) (%) | Amount Dissolved (for Tablets labeled to contain 300 mg of lamotrigine) (%) |
|---|---|---|---|---|---|---|
| 1 | 2 | NMT 30 | NMT 30 | NMT 30 | NMT 35 | NMT 30 |
| 2 | 6 | 38–63 | 38–63 | 38–63 | 40–65 | 34–54 |
| 3 | 10 | 65–90 | 70–95 | 65–95 | 69–94 | 60–83 |
| 4 | 16 | NLT 85 | NLT 85 | NLT 85 | NLT 85 | NLT 85 |
The percentages of the labeled amount of lamotrigine (C9H7Cl2N5 ) dissolved at the times specified conform to Dissolution 〈711〉,
Acceptance Table 2. (RB 1-Jul-2024)
Uniformity of Dosage Units 〈905〉: Meet the requirements
5 IMPURITIES
Change to read:
Organic Impurities
Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.
Diluent 1: Acetonitrile, methanol, and 0.1 N hydrochloric acid (10:20:70)
Diluent 2: Acetonitrile, methanol, and water (10:20:70)
System suitability stock solution: 0.025 mg/mL of USP Lamotrigine Related Compound C RS in Diluent 1
System suitability solution: 1.25 μg/mL of USP Lamotrigine Related Compound C RS and 0.25 mg/mL of USP Lamotrigine RS in Diluent 2
prepared as follows. Transfer a suitable amount of USP Lamotrigine RS to a suitable volumetric flask. Transfer a suitable volume of System suitability stock solution to the flask. Dissolve and dilute with Diluent 2 to volume.
System suitability
Sample: System suitability solution
Suitability requirements
Resolution: NLT 10 between the lamotrigine and lamotrigine related compound C peaks
Signal-to-noise ratio: NLT 100 for lamotrigine related compound C
Analysis
Sample: Sample solution
Calculate the percentage of each degradation product in the portion of Tablets taken:
Result = (rU/rT) × 100
rU = response of each impurity from the Sample solution
rT = sum of all of the impurity peak responses and the lamotrigine peak response from the Sample solution
Acceptance criteria: See Table 15. (RB 1-Jul-2024) Disregard peaks less than 0.05%.
Table 15 (RB 1-Jul-2024)
| Name | Relative Retention Time | Acceptance Criteria, NMT (%) |
|---|---|---|
| Lamotrigine | 1.0 | – |
| Lamotrigine related compound C | 1.7 | 0.3 |
| Lamotrigine dimera | 6.0 | 0.2 |
| Any individual unspecified degradation product | – | 0.2 |
| Total impurities | – | 0.5 |
a This is either lamotrigine o-dimer [N 5 ,N 5′-methylenebis(6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine)] or lamotrigine p-dimer [N3,N3′-methylenebis(6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine)].
6 ADDITIONAL REQUIREMENTS
Packaging and Storage: Preserve in well-closed 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 Lamotrigine RS
USP Lamotrigine Related Compound C RS
3-Amino-6-(2,3-dichlorophenyl)-1,2,4-triazin-5(4H)-one.
C9H7Cl2N5 O 257.08
