Omeprazole Oral Suspension

note: Omeprazole Oral Suspension is not currently licensed in the United Kingdom.

Proton pump inhibitor; treatment of peptic ulcer disease.

Omeprazole Oral Suspension is a suspension containing Omeprazole in a suitable alkaline vehicle.

The oral suspension complies with the requirements stated under Oral Liquids, the requirements stated under Unlicensed Medicines and with the following requirements.

95.0 to 105.0% of the stated amount.

A. Disperse a volume of the oral suspension containing 2 mg of Omeprazole in 0.1m sodium hydroxide and dilute to 100.0 mL with the same solution. Mix with the aid of ultrasound for 10 minutes and filter the resulting suspension. The light absorption, Appendix II B, in the range 230 to 350 nm exhibits absorption 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).

pH, 8.5 to 9.0, Appendix V L.

Complies with the requirements stated under Unlicensed Medicines, Oral Suspensions, using the following method of analysis.

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 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 B).

(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.

(b) Use 700 mL of 0.05m phosphate buffer solution pH 4.5 at a temperature of 37° as the medium.

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

(1) Use a quantity of the oral suspension containing one dose. After 45 minutes, withdraw a 5 mL sample of the medium, filter the aliquot and dilute to 25 mL with solution A.

(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).

(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) For solution (1), allow the chromatography to proceed for 8 times the retention time of omeprazole.

25 volumes of solution B, 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.

The test is not valid unless, in the chromatogram obtained with solution (2), the symmetry factor of the peak due to omeprazole is not more than 2.0.

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

The amount of omeprazole released is not less than 60% (Q) of the stated amount.

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

(1) Disperse a quantity of the oral suspension 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 10 volumes with the mobile phase.

(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 and 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) For solution (1), allow the chromatography to proceed for 3 times the retention time of omeprazole.

27 volumes of acetonitrile and 73 volumes of a 0.14% w/v solution of disodium hydrogen orthophosphate previously adjusted to pH 7.6 with orthophosphoric acid.

When the chromatograms are recorded under the prescribed conditions the retention time of omeprazole is about 9 minutes.

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

In the chromatogram obtained with solution (1):

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

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

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 than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).

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

(1) Disperse a weighed quantity of the oral suspension 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. Dilute 1 volume of the resulting solution 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.

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

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

Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C₁₇H₁₉N₃O₃S, weight in volume, from the chromatograms obtained and using the declared content of C₁₇H₁₉N₃O₃S in omeprazole BPCRS.

Omeprazole Oral Suspension should be protected from light and stored at a temperature of 2° to 8°.

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