NOTE: This monograph has been developed to cover unlicensed formulations.
Action and use
Proton pump inhibitor; treatment of peptic ulcer disease.
DEFINITION
Omeprazole Oral Suspension is a suspension containing Omeprazole in a suitable alkaline vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements. Where appropriate, the oral suspension also complies with the requirements stated under Unlicensed Medicines.
Content of omeprazole, C17H19N3O3S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Disperse a volume of the oral suspension containing 2 mg of Omeprazole in 0.1M sodium hydroxide and dilute to 100 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 at 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
The requirement stated under Unlicensed Medicines, Oral Suspensions does not apply to Omeprazole Oral Suspension.
Buffer capacity
Not less than 400, when determined by the following method.
Measure the pH of 30 mL of the oral suspension, Appendix V L. Add sufficient 0.5M hydrochloric acid to change the initial pH by 1 unit. Calculate the buffer capacity (β) [the amount of strong acid or base that must be added to 1 litre of the solution to change the pH by one unit] using the following expression:
β = VA× 1000 / VS× C
where,
VA = the volume of 0.5M hydrochloric acid required to change the pH by 1 unit (in mL),
VS = the volume of oral suspension (in mL),
C = the concentration of 0.5M hydrochloric acid (in moles per litre).
Related substances
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 1 volume of solution (1) to 20 volumes with the mobile phase. Dilute 1 volume of this solution to 10 volumes with the mobile phase.
(3) Mix 10 mg of each of omeprazole BPCRS and omeprazole impurity D EPCRS in the 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.
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 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.
MOBILE PHASE
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.
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.
LIMITS
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%).
ASSAY
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 of each of omeprazole BPCRS and omeprazole impurity D EPCRS in the mobile phase and dilute to 100 mL with the same solvent.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used but using 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
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.
STORAGE
Omeprazole Oral Suspension should be protected from light and stored at a temperature of 2° to 8°.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Omeprazole.
