Lansoprazole 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

Lansoprazole Delayed-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

[Note—The UV spectra of the major peaks of the Sample solution and the Standard solution as obtained in the Assay may also be used to meet the Acceptance criteria.]

Standard solution: 10 μg/mL of USP Lansoprazole RS in methanol Sample solution: Nominally equivalent to 10 μg/mL of lansoprazole prepared as follows. Powder a portion of Capsule contents equivalent to 5 mg of lansoprazole. Add 5 mL of methanol, shake well, and centrifuge. To 0.1 mL of the supernatant, add 10 mL of methanol.

Acceptance criteria: The UV absorption spectra exhibit a maximum between 281 and 286 nm.

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

3 ASSAY

Procedure

Mobile phase: Acetonitrile, water, and triethylamine (40:60:1). Adjust with phosphoric acid to a pH of 7.0.

Diluent: Acetonitrile, water, and triethylamine (40:60:1). Adjust with phosphoric acid to a pH of 10.0.

System suitability solution: 0.1 mg/mL each of USP Lansoprazole RS and USP Lansoprazole Related Compound A RS in Diluent

Standard stock solution: 3.0 mg/mL of USP Lansoprazole RS in a mixture of acetonitrile and 0.1 M sodium hydroxide (2:3)

Standard solution: 0.09 mg/mL of USP Lansoprazole RS in Diluent, from Standard stock solution

Sample stock solution: Transfer the contents of NLT 10 Capsules, equivalent to 300 mg of lansoprazole, to a 100-mL volumetric flask. Add 60.0 mL of 0.1 M sodium hydroxide and sonicate until completely disintegrated. Add 20.0 mL of acetonitrile and sonicate for about 20 min, dilute with acetonitrile to volume, allow to settle, and use a clear supernatant.

Sample solution: Nominally 0.09 mg/mL of lansoprazole prepared as follows. Transfer 3.0 mL of the Sample stock solution to a 100-mL volumetric flask and dilute with Diluent to volume. Pass the solution through a PVDF filter having a 0.5-μm pore size or another suitable filter, discarding the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1. For Identification A, use a diode array detector in the range of 200–400 nm.

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 5 between lansoprazole and lansoprazole related compound A, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) in the portion of Capsules taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of lansoprazole from the Sample solution

r_S = peak response of lansoprazole from the Standard solution

C_S = concentration of USP Lansoprazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of lansoprazole in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉, Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method A Procedure

Test 1

Acid stage

Acid stage medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm

Time: 60 min

Acid stage standard solution: (L × 0.08/500) mg/mL of USP Lansoprazole RS in Acid stage medium, where L is the label claim, in mg/Capsule

[Note—An amount of methanol NMT 0.5% of the total volume of the Acid stage standard solution may be used to dissolve USP

Lansoprazole RS prior to dilution with Acid stage medium.]

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 306 nm

Blank: Acid stage medium

Analysis: Withdraw a 25-mL aliquot, leaving the remaining 475 mL in the vessel for use in the Buffer stage, and proceed immediately as directed for Buffer stage sample solution. Use a filtered portion of the aliquot as an Acid stage sample solution.

Samples: Acid stage standard solution and Acid stage sample solution

Calculate the percentage of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) dissolved during the Acid stage:

Result = (A_U/A_S)x(C_S/L) × V × 100

A_U= absorbance of the Acid stage sample solution

A_S = absorbance of the Acid stage standard solution

C_S = concentration of USP Lansoprazole RS in the Acid stage standard solution (mg/mL)

L = label claim of lansoprazole (mg/Capsule)

V = volume of Acid stage medium, 500 mL

Tolerances: NMT 10% of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) is dissolved.

Buffer stage

Buffer stage medium: pH 6.8 buffer; 900 mL. Proceed as directed in Buffer stage sample solution.

Apparatus 2: 75 rpm

Time: 60 min

Buffer concentrate: Dissolve 65.4 g of monobasic sodium phosphate, 28.2 g of sodium hydroxide, and 12 g of sodium dodecyl sulfate in 4 L of water.

Blank solution: Acid stage medium and Buffer concentrate (19:17). Adjust, if necessary, with either phosphoric acid or sodium hydroxide

solution to a pH of 6.8.

Buffer stage standard solution: (L × 0.7/900) mg/mL of USP Lansoprazole RS in the Blank solution, where L is the label claim in mg/Capsule

[Note—An amount of methanol NMT 2% of the total volume of the Buffer stage standard solution may be used to dissolve USP Lansoprazole RS prior to dilution with Blank solution.]

Buffer stage sample solution: Add 425 mL of Buffer concentrate to the remaining 475 mL of solution in each vessel from the Acid stage.

Adjust, if necessary, with either phosphoric acid or sodium hydroxide solution to a pH of 6.8, and pass through a suitable filter.

Instrumental conditions

Mode: UV-Vis

Analytical wavelength: About 286 and 650 nm

Blank: Blank solution

Analysis

Samples: Buffer stage standard solution and Buffer stage sample solution

Determine the percentage of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) dissolved using the difference between the

absorbances at the wavelengths of about 286 nm and 650 nm.

Result = (A_U/A_S)x(C_S /L) × V × 100

A_U = difference between absorbances of the Buffer stage sample solution

A_S = difference between absorbances of the Buffer stage standard solution

C_S = concentration of USP Lansoprazole RS in the Buffer stage standard solution (mg/mL)

L = label claim of lansoprazole (mg/Capsule)

V = volume of Buffer stage medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Acid stage: Proceed as directed in Dissolution Test 1.

Tolerances: NMT 10% of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S

Buffer stage: Proceed as directed in Dissolution Test 1, except for the Time.

Time: 45 min

Tolerances: NLT 80% (Q) of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) is dissolved.

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Standard solution: 12 μg/mL of USP Lansoprazole RS in a mixture of acetonitrile and 0.1 M sodium hydroxide (7:3)

Sample solution: Transfer the contents of 1 Capsule to a 100-mL volumetric flask, add 30 mL of 0.1 M sodium hydroxide, and sonicate to disintegrate. Add 65 mL of acetonitrile, cool, and dilute with acetonitrile to volume. Centrifuge a portion of the suspension and pass through a membrane filter having a 0.5-μm or finer pore size. Further dilute a portion of the filtrate with a mixture of acetonitrile and 0.1 M sodium hydroxide (7:3) to obtain a solution having a nominal concentration of about 12 μg/mL of lansoprazole.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 294 nm

Cell: 1 cm

Blank: Acetonitrile and 0.1 M sodium hydroxide (7:3)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lansoprazole (C₁₆H₁₄F₃N₃O₂S) in the Capsule taken:

Result = (A_U/A_S)x(C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Lansoprazole RS in the Standard solution (μg/mL)

C_U = nominal concentration of lansoprazole in the Sample solution (μg/mL)(CN 1-Aug-2023)

5 IMPURITIES

Organic Impurities

[Note—Store and inject the lansoprazole solutions at or below 5° using a cooled autosampler. The solutions are stable for about 24 h when

stored at 5°.]

Solution A: Water

Solution B: Acetonitrile, water, and triethylamine (160:40:1). Adjust with phosphoric acid to a pH of 7.0.

Diluent: Methanol and 0.1 N sodium hydroxide (1:3). Adjust with phosphoric acid to a pH of 10.0.

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system for at least 10 min.

Table 1

System suitability solution: 0.1 mg/mL each of USP Lansoprazole RS and USP Lansoprazole Related Compound A RS in Diluent

Standard solution: 2 μg/mL of USP Lansoprazole RS in Diluent. Use sonication to dissolve.

Sensitivity solution: 0.25 μg/mL of USP Lansoprazole RS in Diluent, from the Standard solution

Sample solution: Nominally 250 μg/mL of lansoprazole prepared as follows. Transfer a portion of Capsules contents, equivalent to about 25 mg of lansoprazole, to a 100-mL volumetric flask. Add 70 mL of Diluent and sonicate with occasional shaking for about 30 min, maintaining the temperature below 10°. Dilute with Diluent to volume, and pass the solution through a PVDF filter having a 0.45-μm pore size or another suitable filter, discarding the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Autosampler temperature: 5°

Flow rate: 0.8 mL/min

Injection volume: 40 μL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 6 between lansoprazole and lansoprazole related compound A, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Capsules taken:

Result = (r_U/r_S)x(C_S/C_U ) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of lansoprazole from the Standard solution

C_S = concentration of USP Lansoprazole RS in the Standard solution (μg/mL)

C_U = nominal concentration of lansoprazole in the Sample solution (μg/mL)

F = relative response factor for each impurity (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a [[(1H-Benzimidazole-2-yl)sulfinyl]methyl]-3-methyl-4-(2,2,2-trifluoroethoxy)-pyridine 1-oxide.

^b 2-({[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl}sulfonyl)benzimidazole.

^c 2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-pyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

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 Lansoprazole RS

USP Lansoprazole Related Compound A RS

2-({[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl}sulfonyl)benzimidazole.

C₁₆H₁₄F₃N₃O₃S 385.36