(Ph. Eur. 11.6 update)
Dispersible Lamotrigine Tablets
Lamotrigine Dispersible Tablets from different manufacturers, whilst complying with the requirements of the monograph, may not be interchangeable.
Action and use
Antiepileptic.
DEFINITION
Lamotrigine Dispersible Tablets contain Lamotrigine in a suitable dispersible basis.
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) Shake a quantity of the powdered tablets containing 20 mg of Lamotrigine in 20 mL, dilute to 100 mL, filter and use the filtrate.
(2) 0.02% w/v of lamotrigine BPCRS.
(3) 0.02% 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 retention time of the principal peak in thechromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).
TESTS
Disintegration
Comply with the requirements for Dispersible Tablets.
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating 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 sample of the medium, filter and dilute 5 mL of the filtrate to 10 mL with 0.3M sodium hydroxide. Measure the absorbance of the solution at 307 nm, Appendix II B, using 0.1M sodium hydroxide in the reference cell. Adjust the concentration with water if necessary.
(2) Prepare a suitable solution of lamotrigine BPCRS in the dissolution medium, using 0.3M sodium hydroxide to produce a solution of the strength expected in solution (1). Measure the absorbance of the solution at 307 nm, Appendix II B, using 0.1M sodium hydroxide in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of lamotrigine, C9H7Cl2N5, in the medium using the declared content of C9H7Cl2N5 in lamotrigine BPCRS.
LIMITS
The amount of lamotrigine released is not less than 80% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 20 mg of Lamotrigine with 40 mL of water and add 40 mL of methanol. Dilute to 100 mL with methanol (40%), filter and use the filtrate.
(2) Dilute 1 volume of solution (1) to 100 volumes with methanol (40%) and dilute 1 volume of the resulting solution to 5 volumes with methanol (40%).
(3) 0.02% w/v of lamotrigine impurity standard BPCRSin methanol (40%).
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 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 any 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 such 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 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Lamotrigine comply with the requirement stated under Tablets using the following method of analysis.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake one tablet with 10 mL of water, add sufficient methanol to produce 25 mL and filter.
(2) 0.008% w/v of lamotrigine BPCRS in methanol (40%).
(3) 0.02% w/v of lamotrigine impurity standard BPCRS in methanol (40%).
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 content of C9H7Cl2N5 in each tablet using the declared content of C9H7Cl2N5 in lamotrigine BPCRS.
ASSAY
For tablets containing less than 2 mg and/or less than 2% w/w of lamotrigine.
Use the average of the individual results determined in the test for Uniformity of content.
For tablets containing 2 mg or more than 2% w/w of lamotrigine.
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 20 mg of Lamotrigine with 60 mL of water, add sufficient methanol to produce 100 mL and filter.
(2) 0.02% w/v of lamotrigine BPCRS in methanol (40%).
(3) 0.02% w/v of lamotrigine impurity standard BPCRS in methanol (40%).
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 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.
