Risedronate Sodium Delayed-Release Tablets

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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click https://www.uspnf.com/rb-risendronate-na-drt-20240426.

1 DEFINITION

Risedronate Sodium Delayed-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂).

2 IDENTIFICATION

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

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

3 ASSAY

3.1 Procedure

Mobile phase: 1.8 g/L of edetate disodium in water. Adjust with 1 N sodium hydroxide solution to a pH of 9.5.

Standard solution: 0.1 mg/mL of USP Risedronate Sodium RS in Mobile phase. Sonicate to dissolve, if necessary.

Sample stock solution: Nominally 1 mg/mL of risedronate sodium from Tablets prepared as follows. Transfer the equivalent of 100 mg of risedronate sodium, from finely powdered Tablets (NLT 20) to a 100-mL volumetric flask and add about 70 mL of Mobile phase. Sonicate with intermittent shaking for about 40 min. Dilute with Mobile phase to volume.

Sample solution: Nominally 0.1 mg/mL of risedronate sodium from the Sample stock solution in Mobile phase. Pass the solution through a suitable filter of 0.22-μm pore size, discarding the first 5 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Columns

Guard: 4.0-mm × 5-cm; 10-μm packing L48

Analytical: 4.0-mm × 25-cm, 10-μm packing L48

Flow rate: 0.8 mL/min

Injection volume: 20 μL

Run time: NLT 2 times the retention time of risedronate

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of risedronate from the Sample solution

r_S = peak response of risedronate from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 Dissolution 〈711〉

Test 1 (RB 1-May-2024)

Acid stage

Acid stage medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm

Time: 2 h

Standard stock solution: 0.7 mg/mL of USP Risedronate Sodium RS in water. Sonicate to dissolve, if necessary.

Acid stage standard solution: 0.007 mg/mL of USP Risedronate Sodium RS from the Standard stock solution in Acid stage medium

Acid stage sample solution: After 2 h in the Acid stage medium, withdraw 10 mL of the solution under test and pass through a suitable filter of 0.45-µm pore size, discarding the first 5 mL.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: UV 262 nm

Path length: 0.5 cm

Blank: Acid stage medium

Analysis

Samples: Acid stage standard solution and Acid stage sample solution

Calculate the percentage of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) dissolved:

Result = (A_U/A_S) × C_S × V × (1/L) × 100

A_U = absorbance of the Acid stage sample solution

A_S = absorbance of the Acid stage standard solution

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

V = volume of Acid stage medium; 500 mL

L = label claim (mg/Tablet)

Tolerances: NMT 10% of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) is dissolved.

Buffer stage

Buffer stage medium: pH 6.8 phosphate buffer; 500 mL

Apparatus 2: 75 rpm

Time: 45 min

Buffer stage standard solution: 0.07 mg/mL of USP Risedronate Sodium RS from the Standard stock solution in Buffer stage medium

Buffer stage sample solution: After 2 h in Acid stage medium, carefully discard the Acid stage medium, add 500 mL of Buffer stage medium to the same vessel, and continue with Buffer stage conditions for another 45 min. After 45 min, withdraw 10 mL of the solution under test and pass through a suitable filter of 0.45-μm pore size, discarding the first 5 mL.

Instrumental conditions: Proceed as directed in the Acid stage except for Blank.

Blank: Buffer stage medium

Analysis

Samples: Buffer stage standard solution and Buffer stage sample solution

Calculate the percentage of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) dissolved:

Result = (A_U/A_S) × C_S × V × (1/L) × 100

A_U = absorbance of the Buffer stage sample solution

A_S = absorbance of the Buffer stage standard solution

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

V = volume of the Buffer stage medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) is dissolved.

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

Acid stage medium: 0.1 N hydrochloric acid; 900 mL

Place 1 Tablet in each of the 12 dissolution vessels and start the dissolution test in Acid stage medium. At the end of the Acid stage, drain the Acid stage medium from all the vessels and retain the Tablets. 6 Tablets are to be used for Acid stage analysis while the remaining 6 Tablets are to be used for Buffer stage testing.

Buffer stage medium: pH 6.8 phosphate buffer (Dissolve 6.8 g of potassium phosphate, monobasic and 0.9 g of sodium hydroxide in 1000 mL of water. Adjust with 10% (w/v) sodium hydroxide solution or 10% (v/v) phosphoric acid to a pH of 6.8, if necessary.); 900 mL

Apparatus 2: 75 rpm, paddle coated with Teflon

Times

Acid stage: 2 h

Buffer stage: 0.5 h

Acid stage standard solution: 0.07 mg/mL of USP Risedronate Sodium RS in Buffer stage medium. Sonicate to dissolve, if necessary.

Buffer stage standard solution: 0.039 mg/mL of USP Risedronate Sodium RS in Buffer stage medium. Sonicate to dissolve, if necessary.

Acid stage sample solution: Transfer each of the 6 Tablets reserved for Acid stage analysis to a separate 50-mL volumetric flask and add about 80% of the flask volume of Buffer stage medium. Sonicate for about 45 min with intermittent shaking. Dilute with Buffer stage medium to volume. Allow to stand for 5 min. Dilute 5 mL with Buffer stage medium to 50 mL. Pass through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Buffer stage sample solution: At the end of the Acid stage, carefully discard the Acid stage medium without losing the Tablets. Add 900 mL of Buffer stage medium to each vessel containing the Tablets reserved for Buffer stage testing, and start the dissolution apparatus. At the time specified, pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Solution A: Dissolve 0.69 g of sodium phosphate, monobasic, 0.64 g of tetrabutylammonium bromide, and 0.55 g of edetate disodium in 1000 mL of water. Adjust with 1 N sodium hydroxide solution to a pH of 7.2.

Mobile phase: Acetonitrile and Solution A (5:95)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 262 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 50°

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 1.3 times the retention time of risedronate

System suitability

Samples: Acid stage standard solution and Buffer stage standard solution

Suitability requirements

Tailing factor: NMT 1.5, Acid stage standard solution and Buffer stage standard solution

Relative standard deviation: NMT 2.0%, Acid stage standard solution and Buffer stage standard solution

Analysis

Samples: Acid stage standard solution, Acid stage sample solution, Buffer stage standard solution, and Buffer stage sample solution

Calculate the percentage of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) dissolved in the Acid stage:

Result = A − [(r_U/r_S) × C_S × V_D × (1/L) × 100]

A = percentage of risedronate sodium as determined in the Assay

r_U = peak response of risedronate from the Acid stage sample solution

r_S = peak response of risedronate from the Acid stage standard solution

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

V_D = dilution volume of the Acid stage sample solution, 500 mL

L = label claim (mg/Tablet)

Calculate the percentage of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) dissolved in the Buffer stage:

Result = (r_U/r_S) × C_S × V × (1/L) × 100

r_U = peak response of risedronate from the Buffer stage sample solution

r_S = peak response of risedronate from the Buffer stage standard solution

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

V = volume of Buffer stage medium, 900 mL

L = label claim (mg/Tablet)

Tolerances

Acid stage: NMT 10% of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) is dissolved.

Buffer stage: NLT 80% (Q) of the labeled amount of risedronate sodium (C₇H₁₀NNaO₇P₂) is dissolved. (RB 1-May-2024)

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Mobile phase and Standard solution: Prepare as directed in the Assay.

System suitability solution: 1 mg/mL of USP Risedronate Sodium RS and 0.1 mg/mL of USP Risedronate Related Compound A RS in Mobile phase. Sonicate to dissolve, if necessary.

Sensitivity solution: 1 μg/mL of USP Risedronate Sodium RS from the Standard solution in Mobile phase

Sample solution: Nominally 1 mg/mL of risedronate sodium from Tablets prepared as follows. Transfer the equivalent of 100 mg of risedronate sodium, from finely powdered Tablets (NLT 20) to a 100-mL volumetric flask and add 25 mL of Mobile phase. Sonicate with intermittent shaking for about 40 min. Dilute with Mobile phase to volume. Pass the solution through a suitable filter of 0.22-μm pore size, discarding the first 5 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm

Columns

Guard: 4.0-mm × 5-cm; 10-μm packing L48

Analytical: 4.0-mm × 25-cm, 10-μm packing L48

Flow rate: 0.8 mL/min

Injection volume: 20 μL

Run time: NLT 3.5 times the retention time of risedronate

System suitability

[Note—The relative retention times for 2-(pyridin-3-yl)acetic acid, risedronate related compound A, and risedronate are 0.22, 0.85, and 1.00, respectively.]

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

Suitability requirements

Resolution: NLT 1.5 between risedronate related compound A and risedronate, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any degradation product in the portion of the Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any degradation product from the Sample solution

r_S = peak response of risedronate from the Standard solution

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

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

Acceptance criteria: See Table 1. The reporting threshold is NMT 0.1%.

Table 1

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at controlled room temperature.

Add the following:

Labeling: The labeling states the Dissolution test used only if Test 1 is not used. (RB 1-May-2024)

USP Reference Standards 〈11〉

USP Risedronate Sodium RS

USP Risedronate Related Compound A RS

[1-Hydroxy-2-(pyridin-2-yl)ethylidene]bis(phosphonic acid), monohydrate.

C₇H₁₁NO₇P₂ · H₂O  301.13