Risedronate Sodium Tablets

» Risedronate Sodium Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of risedronate sodium (C7H10NNaO7P2).

Packaging and storage— Preserve in well-closed containers, and store at controlled room temperature.

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USP Risedronate Sodium RS

USP Risedronate Related Compound A RS
2-Pyridinil isomer [1-hydroxy-2-(2-pyridinyl)ethylidene]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

Identification—

A: Infrared Absorption

197K

Test specimen— Transfer a quantity of Tablets, equivalent to about 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 0.45-µm nylon filter. Add 10 mL of 0.2 M cupric chloride solution, mix well, and allow the solution to stand for about 10 minutes. Add 2 mL of dehydrated alcohol, mix well, and allow the solution to stand for a minimum of one hour, to form a blue precipitate of the copper complex. Collect the precipitate using a 0.45-µm nylon filter, 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 specimen— Dissolve about 50 mg of USP Risedronate Sodium RS in 10 mL of water, and pass the solution through a 0.45-µm nylon filter. Proceed as directed under Test specimen, beginning with “Add 10 mL of 0.2 M cupric chloride solution...”

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.

Dissolution

711

—

for tablets labeled to contain 5 mg or 30 mg or 35 mg:

Medium: water; 500 mL, deaerated.

Apparatus 2: 50 rpm, paddles coated with Teflon.

Time: 30 minutes.

Mobile phase— Proceed as directed in the Assay.

Standard solution— Transfer an accurately weighed quantity of USP Risedronate Sodium RS to a suitable volumetric flask, and dilute with Medium to volume to obtain a solution having a known concentration of about 1 mg of anhydrous risedronate sodium per mL. Further dilute this solution with Medium to obtain a final concentration of about (0.002 × L) mg per mL, where L is the tablet label claim in mg.

Test solution— Use a portion of the solution under test, filtering if necessary.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 263-nm detector and a 4.0-mm ×5-cm column that contains 10-µm packing L48. The flow rate is about 0.8 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for multiple injections is not more than 2%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of risedronate sodium dissolved by the formula:

in which rU and rS are the peak responses obtained from the Test solution and Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 500 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the tablet label claim in mg.

Tolerances— Not less than 80% (Q) of the labeled amount of risedronate sodium is dissolved in 30 minutes.

for tablets labeled to contain at least 75 mg:

Medium: water; 900 mL, deaerated.

Apparatus 2: 50 rpm, paddles coated with Teflon.

Time: 45 minutes.

Standard solution— Transfer an accurately weighed quantity of USP Risedronate Sodium RS to a suitable volumetric flask and dilute with Medium to volume to obtain a solution having a known concentration of about 0.12 mg of anhydrous risedronate sodium per mL.

Test solution— Use a portion of the solution under test. Dilute further with Medium, if necessary.

Procedure— Determine the amount of risedronate sodium dissolved by employing UV absorption at the wavelength of maximum absorbance at about 263 nm, with a background correction at 400 nm on portions of the Test solution, in comparison with a Standard solution, using the Medium as a blank and a 5-mm path-length cell. Calculate the percentage of risedronate sodium dissolved by the formula:

in which AU and AS are the absorbances obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; D is the dilution factor of the Test solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the tablet label claim in mg.

Tolerances— Not less than 75% (Q) of the labeled amount of risedronate sodium is dissolved in 45 minutes.

Uniformity of dosage units

905

: meet the requirements.

Assay—

for products labeled to contain from 5 mg to 35 mg of risedronate sodium:

Mobile phase— Dissolve 1.8 g of edetate disodium in 1000 mL of water, and adjust with 1 N sodium hydroxide to a pH of 9.5 ± 0.1. Make adjustments if necessary (see System Suitability under Chromatography

621

Standard preparation— Dissolve an accurately weighed quantity of USP Risedronate Sodium RS in Mobile phase to obtain a solution having a known concentration of about 0.1–0.15 mg of anhydrous risedronate sodium per mL.

System suitability preparation— Dissolve accurately weighed quantities of USP Risedronate Sodium RS and USP Risedronate Related Compound C RS in Mobile phase to obtain a solution having known concentrations of about 0.15 mg of anhydrous risedronate sodium per mL and about 7.5 µg of risedronate related compound C per mL. [note—USP Risedronate Related Compound C RS is [2-(3-pyridinyl)ethylidene-1,1]bis(phosphonic acid). ]

Assay preparation— Transfer 10 Tablets to a suitable volumetric flask, add Mobile phase to about 60% of the volume of the flask, shake for about 10 minutes, and then sonicate for a minimum of 5 minutes. 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 per mL. Further dilute an aliquot of this solution with Mobile phase to obtain a solution having a known concentration of about 0.1–0.15 mg per mL, based on the label claim. Pass a portion of this solution through a 0.22-µm nylon filter, discarding the first 3 mL of the filtrate.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 263-nm detector and a 4.0-mm × 25-cm column that contains 10-µm packing L48. The flow rate is about 0.8 mL per minute. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the resolution between risedronate related compound C and risedronate is not less than 2.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for three replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in percentage label claim, of C7H10NNaO7P2 in the portion of Tablets taken by the formula:

100(CS / CU)(rU / rS)

in which CS is the concentration, in mg per mL, of risedronate sodium in the Standard preparation; CU is the concentration, in mg per mL, of risedronate sodium in the Assay preparation, based on the label claim; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.

for products labeled to contain at least 75 mg of risedronate sodium:

621

Standard preparation— Dissolve accurately weighed quantities of USP Risedronate Sodium RS and USP Risedronate Related Compound A RS in Mobile phase to obtain a solution having known concentrations of about 0.25 mg of anhydrous risedronate sodium and about 0.004 mg of risedronate related compound A per mL.

Assay preparation— Transfer 10 Tablets to a suitable container, add 400 mL of Mobile phase, cap, and mechanically shake for 5–15 minutes, using an orbital or other suitable shaker. [note—Additional sonication for 5–15 minutes may be performed if necessary. ] Further dilute an aliquot of this solution with Mobile phase to obtain a solution having a known concentration of about 0.2–0.3 mg per mL, based on the label claim. Pass a portion of this solution through a 0.45-µm nylon filter, discarding the first few mL of the filtrate.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 263-nm detector and a 4.0-mm × 25-cm column that contains 10-µm packing L48. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution between risedronate and risedronate related compound A is not less than 2.0; the tailing factor for the risedronate peak is not more than 1.5; and the relative standard deviation for three replicate injections is not more than 1.5% for the risedronate peak.

Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in percentage, of C7H10NNaO7P2 in the portion of the Tablets taken by the formula:

100(CS / CU)(rU / rS)

in which CS is the concentration, in mg per mL, of risedronate sodium in the Standard preparation; CU is the concentration, in mg per mL, of risedronate sodium in the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Elena Gonikberg, Ph.D. Principal Scientific Liaison 1-301-816-8251	(SM32010) Monographs - Small Molecules 3
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

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