ACID RESISTANCE STAGE—
Medium:
0.1 N hydrochloric acid; 500 mL.
Apparatus 2:
100 rpm.
Time:
2 hours.
pH 7.6 Phosphate buffer, Mobile phase, and Chromatographic system—
Proceed as directed for Buffer stage.
Standard solution—
Transfer about 50 mg of
USP Omeprazole RS, accurately weighed, to a 250-mL volumetric flask, dissolve in 50 mL of alcohol, dilute with 0.01 M sodium borate solution to volume, and mix. Transfer 10.0 mL of this solution into a 100-mL volumetric flask, add 20 mL of alcohol, dilute with 0.01 M sodium borate solution to volume, and mix.
Test solution—
After 2 hours, filter the Medium containing the pellets through a sieve with an aperture of not more than 0.2 mm. Collect the pellets on the sieve, and rinse them with water. Using approximately 60 mL of 0.01 M sodium borate solution, carefully transfer the pellets quantitatively to a 100-mL volumetric flask. Sonicate for about 20 minutes until the pellets are broken up. Add 20 mL of alcohol to the flask, dilute with 0.01 M sodium borate solution to volume, and mix. Dilute an appropriate amount of this solution with 0.01 M sodium borate solution to obtain a solution having a concentration of about 0.02 mg per mL. At level L1, test 6 units. Test 6 additional units at level L2, and at level L3, an additional 12 units are tested. Continue testing through the three levels unless the results conform at either L1 or L2.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Standard solution and
Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of omeprazole (C
17H
19N
3O
3S) dissolved in the
Medium by the formula:
T – CD(rU / rS),
in which
T is the labeled quantity, in mg, of omeprazole in the capsule;
C is the concentration, in mg per mL, of
USP Omeprazole RS in the
Standard solution; D is the dilution factor used in preparing the
Test solution; and
rU and
rS are the omeprazole peak responses obtained from the
Test solution and the
Standard solution, respectively.
Tolerances—
Level L1: no individual value exceeds 15% of omeprazole dissolved. Level L2: the average of 12 units is not more than 20% of omeprazole dissolved, and no individual unit is greater than 35% of omeprazole dissolved. Level L3: the average of 24 units is not more than 20% of omeprazole dissolved, not more than 2 units are greater than 35% of omeprazole dissolved, and no individual unit is greater than 45% of omeprazole dissolved.
BUFFER STAGE—
Medium:
pH 6.8 phosphate buffer, 900 mL.
Proceed as directed for Acid resistance stage with a new set of capsules from the same batch. After 2 hours, add 400 mL of 0.235 M dibasic sodium phosphate to the 500 mL of 0.1 N hydrochloric acid medium in the vessel. Adjust, if necessary, with 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.05.
Apparatus 2:
100 rpm.
At the end of 30 minutes, determine the amount of C17H19N3O3S dissolved in pH 6.8 phosphate buffer by employing the following method.
pH 10.4, 0.235 M Dibasic sodium phosphate—
Dissolve 33.36 g of anhydrous dibasic sodium phosphate in 1000 mL of water, and adjust with 2 N sodium hydroxide to a pH of 10.4 ± 0.1.
pH 6.8 Phosphate buffer—
Add 400 mL of 0.1 N hydrochloric acid to 320 mL of pH 10.4, 0.235 M Dibasic sodium phosphate, and adjust with 2 N hydrochloric acid or 2 N sodium hydroxide, if necessary, to a pH of 6.8 ± 0.05.
pH 7.6 Phosphate buffer—
Dissolve 0.718 g of monobasic sodium phosphate and 4.49 g of dibasic sodium phosphate in 1000 mL of water. Adjust with 2 N hydrochloric acid or 2 N sodium hydroxide, if necessary, to a pH of 7.6 ± 0.1. Dilute 250 mL of this solution with water to 1000 mL.
Mobile phase—
Transfer 340 mL of acetonitrile to a 1000-mL volumetric flask, dilute with
pH 7.6 Phosphate buffer to volume, and pass through a membrane filter having a 0.5-µm or finer porosity. Make adjustments if necessary (see
System Suitability under
Chromatography 
621
).
Standard solution 1 (for Capsules labeled 10 mg)—
Dissolve an accurately weighed quantity of
USP Omeprazole RS in alcohol to obtain a solution having a known concentration of about 2 mg per mL. Dilute with
pH 6.8 Phosphate buffer quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.01 mg per mL. Immediately add 2 mL of 0.25 M sodium hydroxide to 10 mL of this solution, and mix.
[NOTE—Do not allow the solution to stand before adding the sodium hydroxide solution.
]
Standard solution 2 (for Capsules labeled 20 mg and 40 mg)—
Proceed as directed for Standard solution 1, except to obtain a solution having a known concentration of about 0.02 mg per mL before mixing with 2 mL of 0.25 M sodium hydroxide.
Test solution 1 (for Capsules containing 10 mg and 20 mg)—
Immediately transfer 5.0 mL of the solution under test to a test tube containing 1.0 mL of 0.25 M sodium hydroxide. Mix well, and pass through a membrane filter having a 1.2-µm or finer porosity. Protect from light.
Test solution 2 (for Capsules labeled 40 mg)—
Immediately transfer 5.0 mL of the solution under test to a test tube containing 2.0 mL of 0.25 M sodium hydroxide and 5 mL of pH 6.8 Phosphate buffer. Mix well, and pass through a membrane filter having a 1.2-µm or finer porosity. Protect from light.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 4.0-mm × 12.5-cm analytical column that contains 5-µm packing L7. The flow rate is about 1.0 mL per minute. Chromatograph the appropriate
Standard solution, and record the peak responses as directed for
Procedure: the column efficiency is not less than 2000 theoretical plates, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the appropriate
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of omeprazole (C
17H
19N
3O
3S) dissolved by the formula:
VCD(rU / rS),
in which
V is the volume of
Medium in each vessel;
C is the concentration, in mg per mL, of
USP Omeprazole RS in the appropriate
Standard solution; D is the dilution factor used in preparing the appropriate
Test solution; and
rU and
rS are the omeprazole peak responses obtained from the appropriate
Test solution and the
Standard solution, respectively.
Tolerances—
For Capsules labeled 10 and 20 mg, not less than 75% (Q) of the labeled amount of C17H19N3O3S is dissolved in 30 minutes. For Capsules labeled 40 mg, not less than 70% (Q) of the labeled amount of C17H19N3O3S is dissolved in 30 minutes. The requirements are met if the quantities dissolved from the product conform to Acceptance Table 1.
and 30
Elution