(Ph. Eur. 11.6 update)
Lamotrigine Tablets from different manufacturers, whilst complying with the requirements of the monograph, may not be interchangeable.
Action and use
Antiepileptic.
DEFINITION
Lamotrigine Tablets contain Lamotrigine.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of lamotrigine, C9H7Cl2N5
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in methanol.
(1) To a quantity of the powdered tablets containing 0.1 g of Lamotrigine add 20 mL of methanol, shake well, dilute to 100 mL with methanol, filter and use the filtrate.
(2) 0.1% w/v of lamotrigine BPCRS.
(3) 0.1% w/v each of lamotrigine BPCRS and carbamazepine BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254.
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air and immediately examine under ultraviolet light (254 nm).
MOBILE PHASE
5 volumes of concentrated ammonia, 10 volumes of methanol and 85 volumes of ethyl acetate.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
B. In the Assay, the chromatogram obtained with solution (1) shows a principal peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2 and rotate the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a 10 mL sample of the medium and filter. Measure the absorbance of the filtrate, Appendix II B, diluted with the dissolution medium if necessary, at the maximum at 267 nm using dissolution medium in the reference cell.
(2) Measure the absorbance of a suitable solution of lamotrigine BPCRS in the dissolution medium.
DETERMINATION OF CONTENT
Calculate the total content of lamotrigine, C9H7Cl2N5, in the medium from the absorbances obtained and using the declared content of C9H7Cl2N5 in lamotrigine BPCRS.
LIMITS
The amount of Lamotrigine released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of 20 volumes of methanol and 80 volumes of 0.1M hydrochloric acid (solution A).
(1) Shake a quantity of the powdered tablets containing 0.20 g of Lamotrigine with 20 mL of methanol, dilute to 100 mL with 0.1M hydrochloric acid, filter and use the filtrate.
(2) Dilute 1 volume of solution (1) to 100 volumes with 0.1M hydrochloric acid and dilute 2 volumes of the resulting solution to 10 volumes with solution A.
(3) 0.2% w/v of lamotrigine impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Spherisorb ODS1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 275 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
0.5 volumes of octylamine, 20 volumes of glacial acetic acid, 100 volumes of acetonitrile, 100 volumes of methanol and 700 volumes of water.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) closely resembles the chromatogram supplied with lamotrigine impurity standard BPCRS and the resolution between the peaks due to lamotrigine and saccharin sodium is at least 5.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of the peak corresponding to impurity A is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of all the secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than 0.5 of the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in solution A described under Related substances.
(1) Shake a quantity of the powdered tablets containing 0.2 g of Lamotrigine with 20 mL of methanol, add sufficient 0.1M hydrochloric acid to produce 100 mL and filter. Dilute 1 volume of the filtrate to 10 volumes with solution A.
(2) Shake 50 mg of lamotrigine BPCRS with 20 mL of methanol and add sufficient 0.1M hydrochloric acid to produce 100 mL.Dilute 2 volumes to 5 volumes with solution A.
(3) 0.2% w/v of lamotrigine impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) closely resembles the chromatogram supplied with lamotrigine impurity standard BPCRS and the resolution between the peaks due to lamotrigine and saccharin sodium is at least 5.0.
DETERMINATION OF CONTENT
Calculate the total content of C9H7Cl2N5 in the tablets using the declared content of C9H7Cl2N5 in lamotrigine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurity A listed under Lamotrigine.
