(Ph. Eur. 11.6 update)
Gastro-resistant Lansoprazole Tablets
Action and use
Proton pump inhibitor; treatment of peptic ulcer disease.
DEFINITION
Lansoprazole Gastro-resistant Tablets contain Lansoprazole. They are covered with a gastro-resistant coating or prepared from granules or particles covered with a gastro-resistant coating.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of lansoprazole, C16H14F3N3O2S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A Shake a quantity of the powdered tablets containing 30 mg of Lansoprazole with 50 mL of methanol, filter and dilute 1 volume to 50 volumes. The light absorption, Appendix II B, in the range 220 nm to 350 nm exhibits a maximum at 285 nm.
B. In the Assay, the chromatogram obtained with solution (1) shows a 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.
Mix 11 volumes of 0.25M trisodium orthophosphate and 22 volumes of 0.5M anhydrous disodium hydrogen orthophosphate, dilute to 100 volumes with water and adjust the pH, if necessary, to 11.0 with orthophosphoric acid or 10M sodium hydroxide, as appropriate (solution A).
Mix 1 volume of 10M sodium hydroxide with 99 volumes of 0.05M phosphate buffer solution pH 4.5 (solution B).
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 150 revolutions per minute.
(b) Use as the media the solutions described sequentially below.
First stage (pH 4.5)
Use as the medium 700 mL of 0.05M phosphate buffer solution pH 4.5. After 45 minutes, withdraw 5 mL of the medium, filter, dilute to 25 mL with solution A and retain the samples for analysis as described below. Proceed immediately to the final stage.
Final stage (pH 6.8)
Within 5 minutes, add 200 mL of solution B at 37° to the vessel. Maintain the rotation speed at 150 revolutions per minute and continue to operate the apparatus for 45 minutes. Withdraw 5 mL of the medium, filter, dilute to 25 mL with solution A and retain the samples for analysis as described below.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) The sample solutions taken above.
(2) Dissolve a sufficient quantity of lansoprazole BPCRS in solution A and dilute with sufficient water to produce a final solution of the same concentration as that expected for solution (1).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
DETERMINATION OF CONTENT
Calculate the total content of C16H14F3N3O2S, in the medium using the declared content of C16H14F3N3O2S in lansoprazole BPCRS.
LIMITS
The amount of lansoprazole released after the first stage is not more than 10% of the stated amount. The amount of lansoprazole released after the final stage 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 protected from light.
Mix 1 volume of triethylamine with 60 volumes of water, adjust the pH to 10.5 using orthophosphoric acid, add 40 volumes of acetonitrile and mix (solvent A).
(1) Shake a quantity of the powdered tablets containing 50 mg of Lansoprazole with 50 mL of solvent A and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with solvent A and dilute a further 1 volume to 5 volumes with solvent A.
(3) Dilute 1 volume of solution (2) to 4 volumes with solvent A.
(4) 0.1% w/v of lansoprazole impurity standard BPCRS in solvent A.
(5) 0.0003% w/v of 2-mercaptobenzimidazole (impurity E) in solvent A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with amidohexadecylsilyl silica gel for chromatography (5 μm) (Supelcosil LC-ABZ is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 285 nm.
(f) Inject 10 μL of each solution.
(g) Identify any peaks in the chromatogram obtained with solution (1) corresponding to lansoprazole impurities A and B using solution (3).
MOBILE PHASE
1 volume of triethylamine, 60 volumes of water, adjusted to pH 6.2 using orthophosphoric acid and mix the solution with 40 volumes of acetonitrile.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to lansoprazole and impurity B is at least 3.0.
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 peak corresponding to impurity B is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.4%);
the area of any peak corresponding to impurity E is not greater than the area of the principal peak in the chromatogram obtained with solution (5) (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 more than 2.0%.
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.05%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in solvent A, protected from light.
Mix 1 volume of triethylamine with 60 volumes of water, adjust the pH to 10.5 using orthophosphoric acid, add 40 volumes of acetonitrile and mix (solvent A).
(1) To a quantity of the powdered tablets containing 50 mg of Lansoprazole add 50 mL of solvent A, shake for 30 minutes and filter. Dilute 1 volume to 5 volumes with solvent A.
(2) 0.02% w/v of lansoprazole BPCRS.
(3) 0.01% w/v of lansoprazole impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to lansoprazole and impurity B is at least 3.0.
DETERMINATION OF CONTENT
Calculate the content of lansoprazole, C16H14F3N3O2S, in the tablets using the declared content of C16H14F3N3O2S in lansoprazole BPCRS.
