Alendronate Sodium Tablets
» Alendronate Sodium Tablets contain an amount of Alendronate Sodium equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of alendronic acid (C4H13NO7P2).
Packaging and storage
Preserve in tight containers. Store between 15 and 30.
Change to read:
Labeling
The labeling indicates weekly dosing where appropriate. When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.3
Identification
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.
Change to read:
Dissolution 711
test 13
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Time:
15 minutes.
Determine the amount of C4H13NO7P2 dissolved by employing the following method.
Buffer solution and Mobile phase
Prepare as directed in the Assay.
0.05% 9-Fluorenylmethyl chloroformate solution
Transfer 100 mg of 9-fluorenylmethyl chloroformate to a 200-mL volumetric flask, dilute with acetonitrile to volume, and mix. Prepare this solution fresh.
Borate buffer
Dissolve 6.2 g of boric acid in approximately 950 mL of water, adjust with 1 N sodium hydroxide to a pH of 9.0, and dilute with water to 1 L.
Diluent
Transfer 176.4 g of sodium citrate dihydrate to a 1000-mL volumetric flask, dissolve in and dilute with Medium to volume, and mix.
Standard stock solution
Dissolve an accurately weighed quantity of USP Alendronate Sodium RS in Medium, and dilute quantitatively and stepwise with the same solvent to obtain a solution having a known concentration corresponding to the concentration that would be obtained by dissolving 1 Tablet in 900 mL of the same Medium. Calculate the concentration, C, in mg per mL, of anhydrous alendronate sodium in this solution.
Standard solution
Transfer 5.0 mL of the Standard stock solution to a 50-mL polypropylene screw-cap centrifuge tube containing 1.0 mL of Diluent and 5.0 mL of Borate buffer, and mix for about 3 minutes. Add 4.0 mL of 0.05% 9-Fluorenylmethyl chloroformate solution, and agitate for about 30 seconds. Allow the solution to stand at room temperature for 25 minutes. Add 25 mL of methylene chloride, and agitate for about 40 seconds. Centrifuge the mixture for 5 minutes. Use a portion of the clear upper aqueous layer.
Reagent blank
Using 5 mL of water, proceed as directed for Standard solution, beginning with to a 50-mL polypropylene screw-cap centrifuge tube.
Test solution
After 15 minutes, withdraw a portion of the solution under test, and centrifuge immediately. Using 5.0 mL of the clear supernatant, proceed as directed for Standard solution, beginning with to a 50-mL polypropylene screw-cap centrifuge tube.
Chromatographic system (see Chromatography 621)
Proceed as directed in the Assay. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the capacity factor, k¢, is not less than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 50 µL) of the Standard solution, the Test solution, and the Reagent blank into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of alendronic acid (C4H13NO7P2) dissolved by the formula:
827.1C(rU / rS)
in which C is defined under the Standard stock solution; and rU and rS are the peak areas obtained from the Test solution and the Standard solution, respectively. [NOTE827.1 is the molecular weight conversion factor (C4H13NO7P2 / C4H12NNaO7P2) multiplied by the volume of the Medium (900 mL).]
Tolerances
Not less than 80% (Q) of the labeled amount of alendronic acid (C4H13NO7P2) is dissolved in 15 minutes. Tablets labeled for weekly dosing: not less than 75% (Q) of the labeled amount of alendronic acid (C4H13NO7P2) is dissolved in 15 minutes.
Test 2
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
3
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Determine the amount of C4H12NNaO7P2·3H2O dissolved as directed in the Assay.
Tolerances
Not less than 80% (Q) of the labeled amount of alendronate sodium (C4H12NNaO7P2·3H2O) is dissolved in 30 minutes.
Uniformity of dosage units 905:
meet the requirements.
Assay
Diluent
Transfer 29.4 g of sodium citrate dihydrate to a 1000-mL volumetric flask, dissolve in and dilute with water to volume, and mix.
Buffer solution
Transfer 14.7 g of sodium citrate dihydrate and 7.05 g of anhydrous dibasic sodium phosphate to a 1000-mL volumetric flask, dissolve in about 900 mL of water, adjust with phosphoric acid to a pH of 8.0, dilute with water to volume, and mix.
0.1% 9-Fluorenylmethyl chloroformate solution
Transfer 250 mg of 9-fluorenylmethyl chloroformate to a 250-mL volumetric flask, dilute with acetonitrile to volume, and mix. Prepare this solution fresh just prior to use.
Borate solution
Transfer 38.1 g of sodium borate to a 1000-mL volumetric flask, dissolve in and dilute with water to volume, and mix.
Mobile phase
Prepare a filtered and degassed mixture of Buffer solution, acetonitrile, and methanol (75:20:5). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard stock preparation
Prepare a solution of USP Alendronate Sodium RS in diluent containing 0.03 mg of anhydrous alendronate sodium per mL.
Standard preparation
Transfer 5.0 mL of the Standard stock preparation to a 50-mL polypropylene screw-cap centrifuge tube containing 5 mL of Borate solution, and mix for about 3 minutes. Add 4 mL of 0.1% 9-Fluorenylmethyl chloroformate solution, and agitate for about 30 seconds. Allow the solution to stand at room temperature for 25 minutes. Add 25 mL of methylene chloride, and agitate for about 40 seconds. Centrifuge the mixture for 10 minutes. Use the clear upper aqueous layer.
Assay stock preparation
Transfer not fewer than 10 Tablets to a 1000-mL volumetric flask. Add 500 mL of Diluent, shake by mechanical means for 30 minutes, and sonicate for 5 minutes. Dilute with Diluent to volume, mix, and centrifuge a portion of this solution. Quantitatively dilute a portion of the clear supernatant to a concentration in a range of 0.02 to 0.03 mg per mL.
Assay preparation
Using 5.0 mL of the Assay stock preparation, proceed as directed for Standard preparation, beginning with to a 50-mL polypropylene screw-cap centrifuge tube.
Reagent blank
Using 5 mL of Diluent, proceed as directed for Standard preparation, beginning with to a 50-mL polypropylene screw-cap centrifuge tube.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 266-nm detector and a 4.1-mm × 25-cm column that contains packing L21. The column is maintained at a constant temperature of about 35. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, is not less than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 50 µL) of the Standard preparation, the Assay preparation, and the Reagent blank into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of alendronic acid (C4H13NO7P2) in the portion of Tablets taken by the formula:
0.919DC(rU / rS)
in which D is the dilution factor for the Assay stock preparation; C is the concentration, in mg per mL, of anhydrous USP Alendronate Sodium RS in the Standard stock preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively. [NOTE0.919 is the molecular weight conversion factor (C4H13NO7P2 / C4H12NNaO7P2).]
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 1446
Pharmacopeial Forum: Volume No. 30(3) Page 804
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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