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Omeprazole Delayed-Release Capsules
» Omeprazole Delayed-Release Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of omeprazole (C17H19N3O3S).
Packaging and storage— Preserve in tight, light-resistant containers. Store between 15 and 30.
Labeling— When more than one Drug Release test is given, the labeling states the Drug Release test used only if Test 1 is not used.
Labeling— When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
(Official April 1, 2006)
Identification—
A: Thin-Layer Chromatographic Identification Test 201
Adsorbent: 0.25-mm chromatographic silica gel mixture, prewashed with methanol.
Diluent: a mixture of methylene chloride and methanol (1:1).
Test solution— Transfer the contents of not fewer than 5 Capsules to a mortar, grind the Capsules, and mix. Transfer a weighed quantity of the powder, equivalent to about 10 mg of omeprazole, to a suitable container. Add 2 mL of Diluent, sonicate for 5 minutes, and allow to settle for 20 minutes before applying to the plate.
Standard solution— Dissolve an accurately weighed quantity of USP Omeprazole RS in Diluent to obtain a solution having a known concentration of about 5 mg per mL.
Developing solvent system: a mixture of methylene chloride saturated with ammonia, methylene chloride, and isopropyl alcohol (2:2:1).
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Drug release
TEST 1, METHOD A 724
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.
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 (C17H19N3O3S) dissolved in the Medium by the formula:
TCD(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 (C17H19N3O3S) 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.
TEST 2 711 If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 2.
ACID RESISTANCE STAGE—
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 1: 100 rpm.
Time: 2 hours.
Procedure— After 2 hours, remove each sample from the basket, and quantitatively transfer into separate volumetric flasks to obtain a solution having a final concentration of about 0.2 mg per mL. Proceed as directed for the Assay preparation in the Assay, starting with “Add about 50 mL of Diluent”. Calculate the quantity, in mg, of omeprazole (C17H19N3O3S) dissolved in the Medium by the formula:
T – CD(rU / rS),
in which T is the assayed 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 Test solution and Standard solution, respectively.
Tolerances— It complies with the following Acceptance Table:
Acceptance Table
Level Criterion
L1 the average of the 6 units is not more than
10% of omeprazole dissolved
L2 the average of the 12 units is not more than
10% of omeprazole dissolved
L3 the average of the 24 units is not more than
10% of omeprazole dissolved
BUFFER STAGE—
Medium: 0.05 M pH 6.8 phosphate buffer; 900 mL (see Reagents, Indicators, and Solutions).
Apparatus 1: 100 rpm.
Time: 45 minutes.
Procedure— Proceed as directed for Acid resistance stage with a new set of capsules from the same batch. After 2 hours, replace the acid Medium with the buffer Medium and continue the test for 45 more minutes. Determine the amount of C17H19N3O3S dissolved from UV absorbances at the wavelength of maximum absorbance at about 305 nm on portions of the solutions under test passed through a 0.2-µm nylon filter, in comparison with a Standard solution having a known concentration of USP Omeprazole RS in the same Medium.
Tolerances— It complies with the Acceptance Table under Dissolution 711 . Not less than 75% (Q) of the labeled amount of C17H19N3O3S is dissolved in 45 minutes.
Dissolution 711
TEST 1
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 (C17H19N3O3S) dissolved in the Medium by the formula:
TCD(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 (C17H19N3O3S) 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.
TEST 2— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
ACID RESISTANCE STAGE—
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 1: 100 rpm.
Time: 2 hours.
Procedure— After 2 hours, remove each sample from the basket, and quantitatively transfer into separate volumetric flasks to obtain a solution having a final concentration of about 0.2 mg per mL. Proceed as directed for the Assay preparation in the Assay, starting with “Add about 50 mL of Diluent”. Calculate the quantity, in mg, of omeprazole (C17H19N3O3S) dissolved in the Medium by the formula:
T – CD(rU / rS),
in which T is the assayed 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 Test solution and Standard solution, respectively.
Tolerances— It complies with the following Acceptance Table:
Acceptance Table
Level Criterion
L1 the average of the 6 units is not more than
10% of omeprazole dissolved
L2 the average of the 12 units is not more than
10% of omeprazole dissolved
L3 the average of the 24 units is not more than
10% of omeprazole dissolved
BUFFER STAGE—
Medium: 0.05 M pH 6.8 phosphate buffer; 900 mL (see Reagents, Indicators, and Solutions).
Apparatus 1: 100 rpm.
Time: 45 minutes.
Procedure— Proceed as directed for Acid resistance stage with a new set of capsules from the same batch. After 2 hours, replace the acid Medium with the buffer Medium and continue the test for 45 more minutes. Determine the amount of C17H19N3O3S dissolved from UV absorbances at the wavelength of maximum absorbance at about 305 nm on portions of the solutions under test passed through a 0.2-µm nylon filter, in comparison with a Standard solution having a known concentration of USP Omeprazole RS in the same Medium.
Tolerances— It complies with Acceptance Table 1 under Dissolution 711 . Not less than 75% (Q) of the labeled amount of C17H19N3O3S is dissolved in 45 minutes.
(Official April 1, 2006)
Uniformity of dosage units 905: meet the requirements.
Chromatographic purity—
Diluent, Solution A, Solution B, Mobile phase, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Prepare as directed for the Standard preparation in the Assay.
Test solution— Use the Assay preparation.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Capsules taken by the formula:
(10C/FA)(ri / rS),
in which C is the concentration, in µg per mL, of USP Omeprazole RS in the Standard solution; F is the relative response factor (see Note below for values); A is the quantity, in mg, of omeprazole in the portion of Capsules taken, as determined in the Assay; ri is the peak response for each impurity obtained from the Test solution; and rS is the peak response for omeprazole obtained from the Standard solution: not more than 0.5% of any individual impurity is found, and not more than 2.0% of total impurities is found. [NOTE—The relative response factor, F, equals 1.6 and 3.1 for peaks with a relative retention time of about 0.33 and 0.64, respectively; and equals 1.0 for peaks obtained from all other impurities.]
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay—
Diluent— Dissolve 7.6 g of sodium borate decahydrate in about 800 mL of water. Add 1.0 g of edetate disodium, and adjust with 50% sodium hydroxide solution to a pH of 11.0 ± 0.1. Transfer the solution to a 2000-mL volumetric flask, add 400 mL of dehydrated alcohol, and dilute with water to volume.
Solution A— Prepare a filtered and degassed solution of 6.0 g of glycine in 1500 mL of water. Adjust with 50% sodium hydroxide solution to a pH of 9.0, and dilute with water to 2000 mL.
Solution B— Use a filtered and degassed mixture of acetonitrile and methanol (85:15).
Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve, by sonicating, an accurately weighed quantity of USP Omeprazole RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.2 mg per mL.
Assay preparation— Weigh and mix the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the mixture, equivalent to about 20 mg of omeprazole, to a 100-mL volumetric flask, add about 50 mL of Diluent, and sonicate for 15 minutes. Cool, dilute with Diluent to volume, mix, and pass through a membrane filter having 0.45-µm or finer porosity. [NOTE—Bubbles may form just before bringing the solution to volume. Add a few drops of dehydrated alcohol to dissipate the bubbles if they persist for more than a few minutes.]
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 305-nm detector and a 4.6-mm × 15-cm column that contains 5-µm base-deactivated packing L7. The flow rate is about 1.2 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)
Solution A
%
Solution B
%
Elution
0–20 88®40 12®60 linear gradient
20–21 40®88 60®12 linear gradient
21–25 88 12 isocratic
Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 20,000 theoretical plates; the tailing factor is not less than 0.8 and not more than 2; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of omeprazole (C17H19N3O3S) in the portion of Capsules taken by the formula:
DC(rU / rS),
in which D is the dilution factor of the Assay preparation; C is the concentration, in mg per mL, of USP Omeprazole RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Elena Gonikberg, Ph.D., Scientist
Expert Committee : (MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
USP29–NF24 Page 1578
Pharmacopeial Forum : Volume No. 31(5) Page 1392
Phone Number : 1-301-816-8251