Risedronate Sodium 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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1 DEFINITION

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

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: Transfer a quantity of Tablets, equivalent to 50–75 mg of risedronate sodium, to a suitable flask. Add 10 mL of water, and shake. Pass first through a suitable paper filter, and then through a nylon filter of 0.45-µm pore size. Add 10 mL of 0.2 M cupric chloride solution, mix well, and allow the solution to stand for about 10 min. Add 2 mL of dehydrated alcohol, mix well, and allow the solution to stand for a minimum of 1 h, to form a blue precipitate of the copper complex. Collect the precipitate using a nylon filter of 0.45-µm pore size, wash it with 10 mL of dehydrated alcohol, and allow it to dry on the filter.

[Note—Dry the precipitate under ambient conditions; do not heat the precipitate. A modest change of color (from blue to green) may be observed upon drying.]

Standard: Dissolve 50 mg of USP Risedronate Sodium RS in 10 mL of water, and pass the solution through a nylon filter of 0.45-µm pore size. Proceed as directed for the Sample, beginning with “Add 10 mL of 0.2 M cupric chloride solution...”

Acceptance criteria: Meet the requirements

B. 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

3.1 Procedure

3.1.1 For Tablets labeled to contain 5–35 mg of risedronate sodium

Mobile phase: 1.8 g/L of edetate disodium in water. Adjust with 1 N sodium hydroxide to a pH of 9.5 ± 0.1.

System suitability solution: 0.15 mg/mL of anhydrous USP Risedronate Sodium RS and 7.5 µg/mL of USP Risedronate Related Compound C RS in Mobile phase

Standard solution: 0.1–0.15 mg/mL of anhydrous USP Risedronate Sodium RS in Mobile phase

Sample stock solution: Transfer 10 Tablets to a suitable volumetric flask, add Mobile phase to about 60% of the volume of the flask, shake for about 10 min, then sonicate for a minimum of 5 min. Cool the solution to room temperature, and dilute with Mobile phase to volume to obtain a solution having a known concentration of about 0.5–1.5 mg/mL.

Sample solution: Nominally 0.1–0.15 mg/mL of risedronate sodium in Mobile phase, dilute from the Sample stock solution. Pass a portion of this solution through a nylon filter of 0.22-µm pore size, discarding the first 3 mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm

Column: 4.0-mm × 25-cm; 10-µm packing L48

Flow rate: 0.8 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.5 between risedronate related compound C and risedronate, System suitability solution

Relative standard deviation: NMT 2.0% for three replicate injections, Standard solution

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%

3.1.2 For Tablets labeled to contain at least 75 mg of risedronate sodium

Mobile phase: 1.8 g/L of edetate disodium in water. Adjust with 1 N sodium hydroxide to a pH of 9.5 ± 0.1.

Standard solution: 0.25 mg/mL of anhydrous USP Risedronate Sodium RS and 4 µg/mL of USP Risedronate Related Compound A RS in Mobile phase

Sample stock solution: Transfer 10 Tablets to a suitable container. Add 400 mL of Mobile phase, cap, and mechanically shake for 5–15 min, using an orbital or other suitable shaker.

[Note—Additional sonication for 5–15 min may be performed if necessary.]

Sample solution: Nominally 0.2–0.3 mg/mL of risedronate sodium in Mobile phase, dilute from the Sample stock solution. Pass a portion of this solution through a nylon filter of 0.45-µm pore size, discarding the first few mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm

Column: 4.0-mm × 25-cm; 10-µm packing L48

Flow rate: 1.0 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between risedronate related compound A and risedronate peaks

Tailing factor: NMT 1.5 for risedronate peak

Relative standard deviation: NMT 1.5% for the risedronate peak from three replicate injections

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

4.1 Dissolution 〈711〉

For Tablets labeled to contain 5, 30, or 35 mg

Medium: Water; 500 mL, deaerated

Apparatus 2: 50 rpm, paddles coated with Teflon

Time: 30 min

Mobile phase: Prepare as directed in the Assay.

Standard stock solution: 1 mg/mL of anhydrous USP Risedronate Sodium RS in Medium

Standard solution: (0.002 × L) mg/mL of USP Risedronate Sodium RS in Medium from the Standard stock solution, where L is the Tablet label claim in mg

Sample solution: Use a portion of the solution under test, filter if necessary.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm

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

Flow rate: 0.8 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2%

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of risedronate from the Sample solution

r_S = peak response of risedronate from the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of risedronate sodium is dissolved.

4.1.1 For Tablets labeled to contain at least 75 mg

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm, paddles coated with Teflon

Time: 45 min

Standard solution: 0.12 mg/mL of anhydrous USP Risedronate Sodium RS in Medium

Sample solution: Use a portion of the solution under test. Dilute with Medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: Wavelength of maximum absorption at about 263 nm, with a background correction at 400 nm

Cell: 5 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

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

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

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

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

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Risedronate Related Compound A RS

2-Pyridinil isomer [1-hydroxy-2-(2-pyridinyl)ethyl idene]bis(phosphonic acid) monohydrate.

C₇H₁₁NO₇P₂  283.12

USP Risedronate Related Compound C RS

[2-(3-Pyridinyl)ethylidene-1,1]bis(phosphonic acid).

C₇H₁₁NO₆P₂  267.11

USP Risedronate Sodium RS