Dissolution (by HPLC)
Dissolution medium: The solutions described sequentially below.
Apparatus: 2 (Paddle).
Speed: 100 rpm.
Run time: 45 minutes.
Solution A: Mix 11 volumes of 0.25 M trisodium orthophosphate and 22 volumes of 0.5 M anhydrous disodium hydrogen orthophosphate, dilute to 100 volumes with water and adjust the pH, if necessary, to 11.0 with orthophosphoric acid or 10 M sodium hydroxide.
Solution B: Mix 1 volume of 10 M Sodium hydroxide with 99 volumes of 0.05 M phosphate buffer solution pH 4.5.
Solution C: Mix 5.2 volumes of 1 M anhydrous sodium dihydrogen orthophosphate and 63.2 volumes of 0.5 M anhydrous disodium hydrogen orthophosphate, dilute to 1000 volumes with water and adjust the pH, if necessary, to 7.6 with orthophosphoric acid or 10 M sodium hydroxide, as appropriate.
First stage (pH 4.5)
Use as the medium 700 ml of 0.05 M 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.
Note: Proceed immediately to the final stage.
Final stage (pH 6.8)
Within 5 minutes, add 200 ml of solution B at 37°C 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.
Using the following solutions.
(1) Use the sample solutions taken above.
(2) Dissolve a sufficient quantity of Omeprazole BPCRS or Omeprazole WS in solution A and dilute with water, the concentration of the final solution should be the same as that expected for solution (1).
(a) 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) Flow rate is 0.25 ml per minute.
(d) Column temperature is 30°C.
(e) Detection wavelength is 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 preparation: 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 10 M Sodium hydroxide, as appropriate.
System suitability: The symmetry factor of the peak due to Omeprazole is not more than 2.0.
Interpretation: The requirements are met if the quantities of active ingredient dissolved from the dosage units tested conform to acceptance table. Continue testing through the three stages unless the results conform at either S1 or S2.
|Stage||Number Tested||Acceptance Criteria|
|S1||6||Each unit is not less than Q+5%.|
|S2||6||Average of 12 units (S1+S2) is equal to or greater than Q and no unit is less than Q-15%.|
|S3||12||Average of 24 units (S1+S2+S3) Equal to or greater than Q, not More than 2 units are less than Q-15% and no unit is less than Q-25%.|
Calculation: Calculate the total content of Omeprazole (C17H19N3O3S) in percent by using given below formula:
Test area Std. dilution Potency (in %)
————————-× ——————× ———————-× 100
Average Std. area Test dilution 100