Omeprazole Delayed-Release Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Omeprazole Delayed-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S).

2 IDENTIFICATION

A. The retention time of the major peak in the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Solution A:

Dissolve 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:

Acetonitrile and methanol (85:15)

Mobile phase: See Table 1.

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.

Standard solution:

0.2 mg/mL of USP Omeprazole RS in Diluent, using sonication as necessary.

Sample solution:

Weigh and mix the contents of NLT 20 Capsules. Transfer an accurately weighed portion of the Capsule content, equivalent to 20 mg of omeprazole, to a 100-mL volumetric flask, add about 50 mL of Diluent, and sonicate for 15 min. Cool, dilute with Diluent to volume, mix, and pass through a membrane filter of 0.45-µm or finer pore size.

[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〉, System Suitability.)

Mode: LC

Detector: UV 305 nm

Column: 4.6-mm × 15-cm; 5-µm base-deactivated packing L7

Flow rate: 1.2 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 20,000 theoretical plates

Tailing factor: 0.8–2

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S) in the portion of Capsules taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Omeprazole RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of omeprazole in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Acid resistance stage

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 100 rpm

Time: 2 h

Buffer C, Mobile phase, Chromatographic system, and System suitability: Proceed as directed for Buffer stage.

Standard solution:

Transfer 50 mg of USP Omeprazole RS to a 250-mL volumetric flask, dissolve in 50 mL of alcohol, and dilute with 0.01 M sodium borate solution to volume. 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.

Sample solution:

After 2 h, filter the Medium containing the pellets through a sieve with an aperture of NMT 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 min 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 containing 0.02 mg/mL. At level L₁, test 6 units. Test 6 additional units at level L₂, and at level L₃, test an additional 12 units. Continue testing through the three levels unless the results conform at either L₁ or L₂.

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S) dissolved in Medium, in mg:

Result = T − Cₛ × D × (rᵤ / rₛ)

T = labeled quantity of omeprazole in the capsule (mg)

Cₛ = concentration of USP Omeprazole RS in the Standard solution (mg/mL)

D = dilution factor used in preparing the Sample solution

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Tolerances

Level L₁: No individual value exceeds 15% of the omeprazole dissolved.

Level L₂: The average of 12 units is NMT 20% of omeprazole dissolved, and no individual unit is greater than 35% of omeprazole dissolved.

Level L₃: The average of 24 units is NMT 20% of omeprazole dissolved, NMT 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 in Acid resistance stage with a new set of Capsules from the same batch. After 2 h, 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 min, determine the amount of omeprazole (C₁₇H₁₉N₃O₃S) dissolved in the pH 6.8 phosphate buffer by using the following method.

Buffer A (0.235 M dibasic phosphate buffer, pH 10.4):

33.36 g/L of anhydrous dibasic sodium phosphate, adjusted with 2 N sodium hydroxide to a pH of 10.4 ± 0.1

Buffer B (phosphate buffer, pH 6.8):

0.1 N hydrochloric acid and Buffer A (5:4), adjusted with 2 N hydrochloric acid or 2 N sodium hydroxide, if necessary, to a pH of 6.8 ± 0.05.

Buffer C (phosphate buffer, pH 7.6):

0.718 g/L of monobasic sodium phosphate and 4.49 g/L of dibasic sodium phosphate, adjusted 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 Buffer C to volume, and pass through a membrane filter of 0.5-µm or finer pore size.

Standard solution A (for Capsules labeled to contain 10 mg):

Prepare a solution containing 2 mg/mL of USP Omeprazole RS in alcohol. Dilute with Buffer B to obtain a solution containing 0.01 mg/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 B (for Capsules labeled to contain 20 or 40 mg):

Proceed as directed for Standard solution A, except to obtain a solution containing 0.02 mg/mL before mixing with 2 mL of 0.25 M sodium hydroxide.

Sample solution A (for Capsules containing 10 or 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 of 1.2-µm or finer pore size. Protect from light.

Sample solution B (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 Buffer B. Mix well, and pass through a membrane filter of 1.2-µm or finer pore size. Protect from light.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm × 12.5-cm; 5-µm packing L7

Flow rate: 1.0 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution A or B, as appropriate

Suitability requirements

Column efficiency: NLT 2000 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S) dissolved:

Result = (rᵤ / rₛ) × (Cₛ / L) × V × D × 100

rᵤ = peak response from the appropriate Sample solution

rₛ = peak response from the appropriate Standard solution

Cₛ = concentration of the appropriate Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

D = dilution factor used in preparing the appropriate Sample solution

Tolerances

For Capsules labeled to contain 10 and 20 mg: NLT 75% (Q) is dissolved.

For Capsules labeled to contain 40 mg: NLT 70% (Q) is dissolved.

The percentages of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S) dissolved at the time specified conform to Acceptance Table 1 in Dissolution 〈711〉.

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 h

Sample solution:

After 2 h, 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/mL. Proceed as directed for the Sample solution in the Assay, starting with “Add about 50 mL of Diluent”.

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S) dissolved in Medium, in mg:

Result = T − Cₛ × D × (rᵤ / rₛ)

T = labeled quantity of omeprazole in the capsule (mg)

Cₛ = concentration of USP Omeprazole RS in the Standard solution (mg/mL)

D = dilution factor used in preparing the Sample solution

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Tolerances: See Table 2.

Buffer stage

Medium: 0.05 M pH 6.8 phosphate buffer; 900 mL (see Reagents, Indicators, and Solutions)

Apparatus 1: 100 rpm

Time: 45 min

Analysis:

Proceed as directed for Acid resistance stage with a new set of Capsules from the same batch. After 2 h, replace the acid Medium with the buffer Medium, and continue the test for 45 more min. Determine the amount of omeprazole (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 nylon filter of 0.2-µm pore size, in comparison with a Standard solution having a known concentration of USP Omeprazole RS in the same Medium.

Tolerances: NLT 75% (Q) is dissolved.

The percentage of the labeled amount of omeprazole (C₁₇H₁₉N₃O₃S) dissolved at the time specified conforms to Acceptance Table 1 in Dissolution 〈711〉.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution:

1.0 µg/mL of USP Omeprazole RS in Diluent

Peak identification solution:

0.2 mg/mL of USP Omeprazole RS, 1.0 µg/mL of USP Omeprazole Related Compound F and G Mixture RS, and 1.0 µg/mL of 5-methoxy-1H-benzimidazole-2-thiol in Diluent. Sonicate the solution for 15 min, and then heat at 55° for 30 min.

[Note—The heating step facilitates conversion of omeprazole related compounds F and G into a product with the relative retention time of 0.33. The remaining unconverted omeprazole related compounds F and G may elute as a very broad peak at the relative retention time of about 0.5.]

Analysis

Samples: Standard solution, Peak identification solution, and Sample solution

Chromatograph the Peak identification solution, and identify the components on the basis of their relative retention times, given in Table 3.

Calculate the percentage of each impurity in the portion of Capsules taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵤ = peak response for each impurity from the Sample solution

rₛ = peak response for omeprazole from the Standard solution

Cₛ = concentration of USP Omeprazole RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of omeprazole in the Sample solution (mg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3.

ᵃ These impurities undergo transformation in the solution to form a conversion product, which elutes at the relative retention time of 0.33.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store between 15° and 30°.

Labeling: When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Omeprazole RS

USP Omeprazole Related Compound F and G Mixture RS

1,3-Dimethyl-8-methoxy-12-thioxopyrido[1′,2′:3,4]imidazo[1,2-a]benzimidazol-2(12H)-one and

1,3-dimethyl-9-methoxy-12-thioxopyrido[1′,2′:3,4]imidazo[1,2-a]benzimidazol-2(12H)-one.