Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Proton pump inhibitor; treatment of peptic ulcer disease.
DEFINITION
Pantoprazole Gastro-resistant Tablets contain Pantoprazole Sodium Sesquihydrate. 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 pantoprazole, C16H15F2N3O4S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing the equivalent of 50 mg of pantoprazole with 10 mL of acetone, filter (Whatman GF/C is suitable) and evaporate to dryness. Dry the residue at 60° for 30 minutes. The infrared absorption spectrum Appendix II A, is concordant with the reference spectrum of pantoprazole sodium ( RS 488).
TESTS
Dissolution
Carry out the dissolution test for tablets and capsules, Appendix XII B1.
First stage (pH 4.5)
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.
(b) Use as the medium 700 mL of 0.05M phosphate buffer solution pH 4.5.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes, withdraw a sample of the medium, and filter the aliquot (0.45-µm PVDF is suitable). Dilute 1 volume of the filtrate to 5 volumes with water, and further dilute, if necessary, with sufficient water to produce a solution expected to contain about 0.00057% w/v of pantoprazole. Proceed immediately to the final stage.
(2) 0.0006% w/v of pantoprazole sodium BPCRS in water.
(3) 0.0018% w/v of pantoprazole sodium BPCRS and 0.0002% w/v of pantoprazole impurity A BPCRS in water.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use isocratic elution using the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use an autosampler temperature of 5°.
(f) Use a detection wavelength of 290 nm.
(g) Inject 50 µL of each solution.
MOBILE PHASE
35 volumes of acetonitrile and 65 volumes of 0.01M dipotassium hydrogen phosphate trihydrate, previously adjusted to pH 7.0 with a 20% v/v solution of orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity A and pantoprazole is at least 1.5.
DETERMINATION OF CONTENT
Calculate the total content of C16H15F2N3O4S in the medium using the declared content of C16H15F2N3O4S in pantoprazole sodium BPCRS.
LIMITS
The amount of pantoprazole released is not more than 10% of the stated amount.
Final stage (about pH 6.8)
Mix 1 volume of 10M sodium hydroxide with 99 volumes of 0.05M phosphate buffer solution pH 4.5 (solution A).
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.
(b) Within 5 minutes of completion of the first stage, add to the vessel 200 mL of solution A, previously held and maintained at 37°.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes, withdraw a sample of the medium, and filter the aliquot (0.45-µm PVDF is suitable). Dilute 1 volume of the filtrate to 5 volumes with water, and further dilute, if necessary, with sufficient water to produce a solution expected to contain about 0.00044% w/v of pantoprazole.
(2) 0.00047% w/v of pantoprazole sodium BPCRS in water.
(3) 0.0018% w/v of pantoprazole sodium BPCRS and 0.0002% w/v of pantoprazole impurity A BPCRS in water.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under the first stage 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 impurity A and pantoprazole is at least 1.5.
DETERMINATION OF CONTENT
Calculate the total content of C16H15F2N3O4S in the medium using the declared content of C16H15F2N3O4S in pantoprazole sodium BPCRS.
LIMITS
The amount of pantoprazole released is not less than 65% (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 40 volumes of mobile phase B and 60 volumes of mobile phase A.
(1) Shake a quantity of whole tablets containing the equivalent of 0.16 g of pantoprazole in 50 mL, mix with the aid of ultrasound and dilute to produce 100 mL. Dilute 5 volumes to 20 volumes.
(2) Dilute 1 volume of solution (1) to 20 volumes. Dilute 1 volume of this solution to 10 volumes.
(3) 0.05% w/v of pantoprazole for system suitability EPCRS.
(4) Dilute 1 volume of solution (2) to 5 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Kromasil C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use an autosampler temperature of 5°.
(f) Use a detection wavelength of 290 nm.
(g) Inject 20 µL of each solution.
MOBILE PHASE
Mobile phase A 0.174% w/v solution of disodium hydrogen orthophosphate, previously adjusted to pH 7.0 with orthophosphoric acid.
Mobile phase B 48 volumes of mobile phase A and 52 volumes of acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-3 | 60 | 40 | isocratic |
| 3-43 | 60→40 | 40→60 | linear gradient |
| 43-48 | 40→60 | 60→40 | linear gradient |
| 48-55 | 60 | 40 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions the retention times relative to pantoprazole (retention time about 16 minutes) are: impurity C, about 0.4; impurity A, about 0.8; impurity D + F, about 1.3; impurity E, about 2.0 and impurity B, about 2.2.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to pantoprazole and impurity D + F is greater than 3.0.
LIMITS
Identify any peak in the chromatogram obtained with solution (1) due to impurity C using the chromatogram obtained with solution (3) and multiply the area of this peak by a correction factor of 0.6.
In the chromatogram obtained with solution (1):
the area of any peak due to impurity A and impurity D + F (combined peak area) is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5% of each);
the area of any other secondary peak is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Prepare a solution containing equal volumes of acetonitrile and 0.001M sodium hydroxide (solution B).
(1) Shake 10 tablets with 50 mL of solution B, mix with the aid of ultrasound and dilute to 100 mL with solution B. Centrifuge and dilute the supernatant liquid with solution B to give a solution containing the equivalent of 0.004% w/v of pantoprazole.
(2) 0.0045% w/v of pantoprazole sodium BPCRS in solution B.
(3) 0.0045% w/v of pantoprazole sodium BPCRS and 0.0005% w/v of pantoprazole impurity A BPCRS in solution B.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 20 µL.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity A and pantoprazole is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C16H15F2N3O4S in the tablets from the chromatograms obtained and using the declared content of C16H15F2N3O4S in pantoprazole sodium BPCRS.
LABELLING
The quantity of the active ingredient is stated in terms of the equivalent amount of pantoprazole.
IMPURITIES
The impurities limited by this monograph include those listed under Pantoprazole Sodium Sesquihydrate.
