Metformin Hydrochloride Tablets

» Metformin Hydrochloride Tablets contain not less than 95.0 percent and not more than 105.0 percent of metformin hydrochloride (C4H11N5·HCl).

Packaging and storage— Preserve in tight containers. 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

—

USP Metformin Hydrochloride RS

Identification—

A: Infrared Absorption

197K

Test specimen— Transfer a quantity of powdered Tablets, equivalent to about 20 mg of metformin hydrochloride, to a suitable flask, add 20 mL of dehydrated alcohol, and shake. Filter, evaporate the filtrate on a water bath to dryness, and dry the residue at 105

for 2 hours.

B: Triturate a quantity of the powdered Tablets, equivalent to about 50 mg of metformin hydrochloride, with 10 mL of water, and filter. To 5 mL of the filtrate add 1.5 mL of 5 N sodium hydroxide solution and 1 mL of a 1-naphthol solution, prepared by dissolving 1 g of 1-naphthol in a solution containing 6 g of sodium hydroxide and 16 g of anhydrous sodium carbonate in 100 mL of water. Add 0.5 mL of sodium hypochlorite TS, dropwise, and with shaking: an orange-red color is produced that darkens on standing.

C: Triturate a quantity of the powdered Tablets, equivalent to about 50 mg of metformin hydrochloride, with 10 mL of water, and filter. The filtrate meets the requirements of the tests for Chloride

191

Dissolution

711

—

test 1—

Medium: pH 6.8 phosphate buffer; 1000 mL.

Apparatus 1: 100 rpm.

Time: 45 minutes.

Procedure— Determine the amount of C4H11N5·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 233 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Metformin Hydrochloride RS in the same Medium.

Tolerances— Not less than 70% (Q) of the labeled amount of C4H11N5·HCl is dissolved in 45 minutes.

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

for products labeled to contain 500 mg of metformin—

Medium: pH 6.8 phosphate buffer; 1000 mL.

Apparatus 2: 50 rpm.

Time: 30 minutes.

Procedure— Proceed as directed for Test 1.

Tolerances— Not less than 80% (Q) of the labeled amount of C4H11N5·HCl is dissolved in 30 minutes.

for products labeled to contain 850 mg or 1000 mg of metformin—

Medium: pH 6.8 phosphate buffer; 1000 mL.

Apparatus 2: 75 rpm.

Time: 30 minutes.

Procedure— Proceed as directed for Test 1.

Tolerances— Not less than 75% (Q) of the labeled amount of C4H11N5·HCl is dissolved in 30 minutes.

test 3— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: pH 6.8 phosphate buffer; 1000 mL.

Apparatus 1: 100 rpm.

Time: 60 minutes.

Determine the amount of C4H11N5·HCl dissolved by employing the following method.

0.05 M Sodium phosphate with 1-pentanesulfonic acid solution— Dissolve 1.38 g of monobasic sodium phosphate in about 1800 mL of water. Add 3.484 g of 1-pentanesulfonic acid sodium salt, and mix. Adjust with diluted phosphoric acid to a pH of 3.00 ± 0.05. Add water to make 2000 mL, and mix.

Mobile phase— Prepare a filtered and degassed mixture of 0.05 M Sodium phosphate with 1-pentanesulfonic acid solution and acetonitrile (19:1). Make adjustments if necessary (see System Suitability under Chromatography

621

Standard stock solution— Transfer about 25 mg, accurately weighed, of USP Metformin Hydrochloride RS to a 100-mL volumetric flask, and add about 50 mL of Medium. Sonicate until dissolved, and dilute with Medium to volume.

Standard solution— Transfer 10.0 mL of the Standard stock solution to a 50-mL volumetric flask, and dilute with Medium to volume.

Test solution— Withdraw a portion of the solution under test, and pass through a 0.45-µm nylon filter. Dilute with Medium, if necessary, to obtain a concentration similar to that of the Standard solution.

Chromatographic system— The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. Chromatograph replicate injections of the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; the column efficiency is not less than 1500 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 40 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of metformin released by the formula:

in which rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of metformin in the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; D is the dilution factor of the Test solution; and LC is the Tablet label claim, in mg.

Tolerances— Not less than 70% (Q) of the labeled amount of C4H11N5·HCl is dissolved in 60 minutes.

Uniformity of dosage units

905

: meet the requirements.

Related compounds—

Mobile phase, Resolution solution, and Chromatographic system— Proceed as directed in the test for Related compounds under Metformin Hydrochloride.

Test solution— Weigh and finely powder not fewer than 20 Tablets. Transfer a portion of the powder, equivalent to about 500 mg of metformin hydrochloride, to a 100-mL volumetric flask, dissolve in Mobile phase, with shaking, dilute with Mobile phase to volume, and mix. Filter, and use the filtrate.

Diluted test solution— Proceed as directed in the test for Related compounds under Metformin Hydrochloride, except to use the Test solution prepared as described herein.

Procedure— Separately inject equal volumes (about 20 µL) of the Test solution and the Diluted test solution into the chromatograph, record the chromatograms for not less than twice the retention time of metformin, and measure the peak areas.

Calculate the percentage of each impurity in the portion of Tablets taken by the formula:

0.1(ri / rS)

in which ri is the peak response for each individual impurity obtained from the Test solution; and rS is the metformin peak response obtained from the Diluted test solution: not more than 0.1% of any impurity is found; and not more than 0.6% of total impurities is found.

Assay—

Standard preparation— Prepare a solution of USP Metformin Hydrochloride RS in water having a known concentration of about 10 µg per mL.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of metformin hydrochloride, to a 100-mL volumetric flask. Add 70 mL of water, shake by mechanical means for 15 minutes, dilute with water to volume, and filter, discarding the first 20 mL of the filtrate. Dilute 10.0 mL of the filtrate with water to 100.0 mL, and dilute 10.0 mL of the resulting solution with water to 100.0 mL.

Procedure— Concomitantly determine the absorbances of the Standard preparation and the Assay preparation, in 1-cm cells, at the wavelength of maximum absorbance at about 232 nm, with a suitable spectrophotometer, using water as a blank. Calculate the quantity, in mg, of metformin hydrochloride (C4H11N5·HCl) in the portion of Tablets taken by the formula:

10C(AU / AS)

in which C is the concentration, in µg per mL, of USP Metformin Hydrochloride RS in the Standard preparation; and AU and AS are the absorbances 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

USP35–NF30 Page 3830

Pharmacopeial Forum: Volume No. 32(6) Page 1725