Gastro-resistant Omeprazole Capsules

General Notices

Action and use

Proton pump inhibitor; treatment of peptic ulcer disease.

DEFINITION

Gastro-resistant Omeprazole Capsules contain Omeprazole. They are covered with a gastro-resistant coating or prepared from granules or particles covered with a gastro-resistant coating.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of omeprazole, C17H19N3O3S

95.0 to 105.0% of the stated amount.

IDENTIFICATION

A. Shake a quantity of the finely powdered contents of the capsules containing 20 mg of Omeprazole with 50 mL of 0.1M sodium hydroxide, dilute to 100 mL, filter and further dilute 10 mL to 100 mL. The light absorption, Appendix II B, in the range 230 to 350 nm exhibits two maxima, at 276 nm and 305 nm.

B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).

TESTS

Dissolution

Carry out 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 withorthophosphoric 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).

Mix 5.2 volumes of 1M anhydrous sodium dihydrogen orthophosphate and 63.2 volumes of 0.5M anhydrous disodium hydrogen orthophosphate, dilute to 1000 volumes with water and adjust the pH, if necessary, to 7.6 with orthophosphoric acid or 10M sodium hydroxide, as appropriate (solution C).

TEST CONDITIONS

(a) Use Apparatus 2, rotating the paddle at 100 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 the aliquot, 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 100 revolutions per minute and continue to operate the apparatus for 45 minutes. Withdraw 5 mL of the medium, filter the aliquot, 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) Use the sample solutions taken above.

(2) Dissolve a sufficient quantity of omeprazole BPCRS in solution A and dilute with water; the concentration of the final solution should be the same as that expected for solution (1).

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (15 cm × 2 mm) packed with octadecylsilyl silica gel for chromatography R(5 µm) (Nucleosil C18 is suitable). Use a suitable guard column.

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 0.25 mL per minute.

(d) Use a column temperature of 30°.

(e) Use a detection wavelength of 302 nm.

(f) Inject 10 µL of each solution.

(g) Allow the chromatography to proceed for 8 times the retention time of omeprazole.

MOBILE PHASE

25 volumes of solution C, 35 volumes of water and 40 volumes of acetonitrile. Adjust the pH, if necessary, to 7.6 with orthophosphoric acid or 10M sodium hydroxide, as appropriate.

SYSTEM SUITABILITY

The symmetry factor of the peak due to omeprazole is not more than 2.0.

DETERMINATION OF CONTENT

Calculate the total content of C17H19N3O3S in the medium using the declared content of C17H19N3O3S inomeprazole BPCRS.

LIMITS

The amount of omeprazole released after the first stage is not more than 10% of the stated amount. The amount of omeprazole released after the final stage is not less than 65% (Q) of the stated amount.

Impurity C

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

Prepare a mixture of equal volumes of methanol and dichloromethane (solvent A).

(1) Weigh the contents of 20 capsules and grind to a fine powder. Disperse a quantity of the powder containing 50 mg of Omeprazole in 15 mL of solvent A, mix with the aid of ultrasound for 30 minutes, dilute with solvent A to produce 20 mL, mix and filter. Evaporate the filtrate to dryness and dissolve the residue in 1 mL of solvent A.

(2) Dilute 1 volume of solution (1) to 50 volumes with solvent A. Dilute 1 volume of this solution to 10 volumes with solvent A.

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, dry in air and examine under ultraviolet light (254 nm).

MOBILE PHASE

20 volumes of propan-2-ol, 40 volumes of dichloromethane previously shaken with concentrated ammonia(shake 100 mL of dichloromethane with 30 mL of concentrated ammonia in a separating funnel; allow the layers to separate and use the lower layer) and 40 volumes of dichloromethane.

LIMITS

Any spot in the chromatogram obtained with solution (1) with a higher Rf value than that of the spot due toomeprazole is not more intense than the spot in the chromatogram obtained with solution (2) (0.2%).

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Weigh the contents of 20 capsules and grind to a fine powder. Disperse a quantity of the powder containing 24 mg of Omeprazole in 150 mL of mobile phase, mix with the aid of ultrasound for 30 minutes, dilute with sufficient mobile phase to produce 200 mL, mix and filter.

(2) Dilute 5 volumes of solution (1) to 100 volumes with the mobile phase. Dilute 1 volume of this solution to 10 volumes with the mobile phase.

(3) Mix 10 mg each of omeprazole BPCRS and omeprazole impurity D EPCRS in mobile phase and dilute to 100 mL with the same solvent.

(4) Dilute 1 volume of solution (2) to 5 volumes with the mobile phase.

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography(5 µm) (Nucleosil RP8 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 a detection wavelength of 280 nm.

(f) Inject 40 µL of each solution.

(g) Allow the chromatography to proceed for 3 times the retention time of omeprazole.

MOBILE PHASE

27 volumes of acetonitrile and 73 volumes of a 0.14% w/v solution of disodium hydrogen orthophosphatepreviously adjusted to pH 7.6 with 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 D and omeprazole is at least 3.0 and the retention time of omeprazole is about 9 minutes.

LIMITS

In the chromatogram obtained with solution (1):

the area of any peak due to impurity D or any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the sum of the areas of any secondary peaks is not greater than four times the area of the principal peak in the chromatogram obtained with solution (2) (2.0%).

Disregard any peak with an area less that 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.

(1) Shake a quantity of the mixed contents of 20 capsules containing 24 mg of Omeprazole in 150 mL of mobile phase, mix with the aid of ultrasound for 30 minutes, dilute with sufficient mobile phase to produce 200 mL, mix and filter and further dilute 1 volume to 10 volumes with the mobile phase.

(2) 0.0012% w/v of omeprazole BPCRS in the mobile phase.

(3) Mix 10 mg each of omeprazole BPCRS and omeprazole impurity D EPCRS in mobile phase and dilute to 100 mL with the same solvent.

CHROMATOGRAPHIC CONDITIONS

The chromatographic conditions described under Related substances may be used but with a detection wavelength of 305 nm.

SYSTEM SUITABILITY

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity D and omeprazole is at least 3.0.

DETERMINATION OF CONTENT

Calculate the content of C17H19N3O3S in the capsules using the declared content of C17H19N3O3S inomeprazole BPCRS.

IMPURITIES

The impurities limited by this monograph include those listed under Omeprazole.