Metformin Hydrochloride Extended-Release Tablets
DEFINITION
Metformin Hydrochloride Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of metformin hydrochloride (C4H11N5·HCl).
IDENTIFICATION
• The retention time of the major peak from the Sample solution corresponds to that from the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer solution:
0.5 g/L of sodium heptanesulfonate and 0.5 g/L of sodium chloride in water. Before final dilution, adjust with 0.06 M phosphoric acid to a pH of 3.85.
Mobile phase:
Acetonitrile and Buffer solution (1:9). [Note—To improve the separation, the composition of acetonitrile and Buffer solution may be changed to 1:19, if necessary. ]
Diluent:
1.25% solution of acetonitrile in water
Standard solution:
(L/4000) mg/mL of USP Metformin Hydrochloride RS in Diluent, where L is the labeled quantity, in mg, of metformin hydrochloride in each Tablet
System suitability stock solution:
12.5 µg/mL of each of USP Metformin Related Compound B RS and USP Metformin Related Compound C RS in Diluent
System suitability solution:
Dilute 0.5 mL of the System suitability stock solution with the Standard solution to 50 mL.
Sample stock solution:
Finely powder NLT 10 Tablets. Transfer powder, equivalent to the average Tablet weight, to a homogenization vessel, and add 500 mL of 10% acetonitrile solution. Alternately, homogenize and allow to soak until the sample is fully homogenized. [Note—A suggested homogenization sequence is as follows. Homogenize the sample using five pulses, each of 5 s, at about 20,000 rpm, and allow to soak for 2 min. Repeat these steps two additional times. ]
Sample solution:
Pass a portion of the Sample stock solution through a suitable filter of 0.45-µm pore size, discarding the first 3 mL of filtrate. Transfer 25 mL of the filtrate to a 200-mL volumetric flask, and dilute with water to volume.
Chromatographic system
Mode:
LC
Detector:
UV 218 nm
Column:
3.9-mm × 30-cm; 10-µm packing L1
Column temperature:
30
Flow rate:
1 mL/min
Injection size:
10 µL
Run time:
Until after the elution locus of metformin related compound C
System suitability
Sample:
System suitability solution
[Note—The relative retention times for metformin related compound B, metformin, and metformin related compound C are 0.86, 1.0, and 2.1–2.3, respectively. Metformin related compound C can have a variable retention time. The composition of the Mobile phase may be changed to 1:19, if it elutes at a relative retention time of less than 2.1. ]
Suitability requirements
Resolution:
NLT 1.5 between peaks due to metformin related compound B and metformin
Tailing factor:
NLT 0.8 and NMT 2.0 for the metformin peak
Relative standard deviation:
NMT 1.5% for the metformin peak and NMT 10% for each of the peaks due to metformin related compound B and metformin related compound C
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C4H11N5·HCl in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Metformin Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of metformin hydrochloride in the Sample solution |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Test 1
Medium:
pH 6.8 phosphate buffer (6.8 g of monobasic potassium phosphate in 1000 mL of water; adjust with 0.2 N sodium hydroxide to a pH of 6.8 ± 0.1); 1000 mL
Apparatus 1:
100 rpm for Tablets labeled to contain 750 mg
Apparatus 2:
100 rpm for Tablets labeled to contain 500 mg
Times:
1, 3, and 10 h
Detector:
UV 232 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable hydrophilic polyethylene filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Calculate the percentage of C4H11N5·HCl released at each time point:
Result = [(AU/AS) × CS × (V 
VS) + (C60 × VS) + (C180 × VS) × 100]/L
VS) + (C60 × VS) + (C180 × VS) × 100]/L| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C60 | = | = concentration of metformin hydrochloride in Medium determined at 1 h (mg/mL) |
| C180 | = | = concentration of metformin hydrochloride in Medium determined at 3 h (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved, 500-mg Tablet |
Amount Dissolved, 750-mg Tablet |
|---|---|---|
| 1 | 20%–40% | 22%–42% |
| 3 | 45%–65% | 49%–69% |
| 10 | NLT 85% | NLT 85% |
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
Prepare as directed for Test 1; 1000 mL.
Apparatus 2:
100 rpm
Times:
1, 2, 6, and 10 h
Detector:
UV 232 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable polyethylene filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration that is similar to the Standard solution.
Analysis:
Calculate, in mg/mL, the content of C4H11N5·HCl, Ct, in Medium at each time point, t:
Result = [AU × CS × DU]/AS
| AU | = | = absorbance of the Sample solution |
| CS | = | = concentration of metformin hydrochloride in the Standard solution (mg/mL) |
| DU | = | = dilution factor of the solution under test |
| AS | = | = absorbance of the Standard solution |
Calculate the percentage of C4H11N5·HCl dissolved at each time point by the following formulas.
Percentage dissolved at the first time point (1 h):
Result = [C1 × V × 100]/L
| C1 | = | = content of metformin hydrochloride in Medium at the first time interval (mg/mL) |
| V | = | = volume of Medium, 1000 mL |
| L | = | = label claim (mg/Tablet) |
Percentage dissolved at the second time point (2 h):
Result = [C2 × (V SV1) + C1 × SV1 × 100]/L
SV1) + C1 × SV1 × 100]/L| C2 | = | = content of metformin hydrochloride in Medium at the second time interval (mg/mL) |
| V | = | = volume of Medium, 1000 mL |
| SV1 | = | = volume of the sample withdrawn at 1 h (mL) |
| C1 | = | = content of metformin hydrochloride in Medium at 1 h (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Percentage dissolved at the nth time point:
Result = {Cn × [V (n 1)VS] + (C1 + C2 + … + Cn1) × VS × 100}/L
(n 1)VS] + (C1 + C2 + … + Cn1) × VS × 100}/L| Cn | = | = content of metformin hydrochloride in Medium at the nth time interval (mg/mL) |
| V | = | = volume of Medium, 1000 mL |
| n | = | = time interval of interest |
| VS | = | = volume of sample withdrawn at each time interval (mL) |
| C | = | = as C1, C2, C3, … Cn–1, the content of metformin hydrochloride in Medium at each time interval (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 20%–40% |
| 2 | 35%–55% |
| 6 | 65%–85% |
| 10 | NLT 85% |
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium, Apparatus 1, Apparatus 2, and Analysis:
Proceed as directed in Test 1.
Times:
1, 2, 5, and 12 h for Tablets labeled to contain 500 mg; and 1, 3, and 10 h for Tablets labeled to contain 750 mg
Detector:
UV 232 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable hydrophilic polyethylene filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Calculate the percentage of C4H11N5·HCl released at each time point:
Result = {[(AU/AS) × CS × (V VS) + (C60 × VS) + (C120 × VS) + (C300 × VS) + (C720 × VS)] × 100}/L
VS) + (C60 × VS) + (C120 × VS) + (C300 × VS) + (C720 × VS)] × 100}/L| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C60 | = | = concentration of metformin hydrochloride in Medium determined at 1 h (mg/mL) |
| C120 | = | = concentration of metformin hydrochloride in Medium determined at 2 h (mg/mL) |
| C300 | = | = concentration of metformin hydrochloride in Medium determined at 5 h (mg/mL) |
| C720 | = | = concentration of metformin hydrochloride in Medium determined at 12 h (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
For Tablets Labeled to Contain 500 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 20%–40% |
| 2 | 35%–55% |
| 5 | 60%–80% |
| 12 | NLT 85% |
For Tablets Labeled to Contain 750 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 22%–42% |
| 3 | 49%–69% |
| 10 | NLT 85% |
Test 4:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium:
Prepare as directed for Test 1; 1000 mL.
Apparatus 2:
100 rpm
Times:
1, 3, 6, and 10 h
Detector:
UV 250 nm (shoulder)
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Calculate, in mg/mL, the content of C4H11N5·HCl, Ct, in Medium at each time point, t, by the formulas specified in Test 2.
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 20%–40% |
| 3 | 45%–65% |
| 6 | 65%–85% |
| 10 | NLT 85% |
Test 5:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Medium:
pH 6.8 phosphate buffer (6.8 g of monobasic potassium phosphate in 1000 mL of water; adjust with 0.2 N sodium hydroxide to a pH of 6.8 ± 0.1); 900 mL, deaerated
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Times:
2, 8, and 16 h
Detector:
UV 250 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Place a vertical sample holder into each basket (see Figures 1 and 2). Place 1 Tablet inside the sample holder, making sure that the Tablets are vertical at the bottom of the baskets.
Calculate, in mg/mL, the content of C4H11N5·HCl, Ct, in Medium at each time point, t, by the formulas specified in Test 2.
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved, 500-mg Tablet |
Amount Dissolved, 1000-mg Tablet |
|---|---|---|
| 2 | NMT 30% | NMT 30% |
| 8 | 60%–85% | 65%–90% |
| 16 | NLT 90% | NLT 90% |
Test 6:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.
Medium:
pH 6.8 phosphate buffer (6.8 g of monobasic potassium phosphate in 1000 mL of water; adjust with 0.2 N sodium hydroxide to a pH of 6.8 ± 0.05); 1000 mL, deaerated
Apparatus 2:
100 rpm, with USP sinker, if necessary
Detector:
UV 233 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable hydrophilic polyethylene filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Calculate the percentage of C4H11N5·HCl released at each time point:
Result = {[(AU/AS) × CS × (V VS) + (C60 × VS) + (C180 × VS) + (C600 × VS)] × 100}/L
VS) + (C60 × VS) + (C180 × VS) + (C600 × VS)] × 100}/L| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C60 | = | = concentration of metformin hydrochloride in Medium determined at 1 h (mg/mL) |
| C180 | = | = concentration of metformin hydrochloride in Medium determined at 3 h (mg/mL) |
| C600 | = | = concentration of metformin hydrochloride in Medium determined at 10 h (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved, 500-mg Tablet |
Amount Dissolved, 750-mg Tablet |
|---|---|---|
| 1 | 20%–40% | 20%–40% |
| 3 | 45%–65% | 45%–65% |
| 10 | NLT 85% | NLT 85% |
Test 7:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.
Medium:
Prepare as directed in Test 1; 1000 mL.
Apparatus 1:
100 rpm for Tablets labeled to contain 750 mg
Apparatus 2:
50 rpm, with USP sinker, for Tablets labeled to contain 500 mg
Times:
1, 3, and 10 h
Detector:
UV 232 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Calculate the percentage of C4H11N5·HCl released at each time point:
Result = {[(AU/AS) × CS × (V VS) + (C60 × VS) + (C180 × VS) + (C600 × VS)] × 100}/L
VS) + (C60 × VS) + (C180 × VS) + (C600 × VS)] × 100}/L| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C60 | = | = concentration of metformin hydrochloride in Medium determined at 1 h (mg/mL) |
| C180 | = | = concentration of metformin hydrochloride in Medium determined at 3 h (mg/mL) |
| C600 | = | = concentration of metformin hydrochloride in Medium determined at 10 h (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved, 500-mg Tablet |
Amount Dissolved, 750-mg Tablet |
|---|---|---|
| 1 | 20%–40% | 20%–40% |
| 3 | 45%–65% | 40%–60% |
| 10 | NLT 85% | NLT 80% |
Test 8:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 8.
Medium:
Prepare as directed in Test 1; 1000 mL.
Apparatus 1:
100 rpm for Tablets labeled to contain 750 mg
Apparatus 2:
100 rpm, with sinker, for Tablets labeled to contain 500 mg
Times:
1, 2, 6, and 10 h
Detector:
UV 232 nm
Standard solution:
USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute, if necessary, with Medium to a concentration similar to the Standard solution.
Analysis:
Calculate the percentage of C4H11N5·HCl released at each time point:
Result = {[(AU/AS) × CS × (V VS) + (C60 × VS) + (C120 × VS) + (C360 × VS) + (C600 × VS)] × 100}/L
VS) + (C60 × VS) + (C120 × VS) + (C360 × VS) + (C600 × VS)] × 100}/L| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C60 | = | = concentration of metformin hydrochloride in Medium determined at 1 h (mg/mL) |
| C120 | = | = concentration of metformin hydrochloride in Medium determined at 2 h (mg/mL) |
| C360 | = | = concentration of metformin hydrochloride in Medium determined at 6 h (mg/mL) |
| C600 | = | = concentration of metformin hydrochloride in Medium determined at 10 h (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved, 500-mg Tablet |
Amount Dissolved, 750-mg Tablet |
|---|---|---|
| 1 | 20%–40% | 20%–40% |
| 2 | 30%–50% | 35%–55% |
| 6 | 65%–85% | 75%–95% |
| 10 | NLT 85% | NLT 85% |
Test 9:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 9.
Medium:
0.05 M phosphate buffer, pH 6.8; 1000 mL
Apparatus 1:
100 rpm, for Tablets labeled to contain 750 mg
Apparatus 2:
100 rpm, for Tablets labeled to contain 500 mg
Times:
1, 5, 12, and 20 h for Tablets labeled to contain 500 mg; and 1, 4, 10, and 24 h for Tablets labeled to contain 750 mg
Standard solution:
0.5 mg/mL of USP Metformin Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Detector:
UV 232 nm
Path length:
0.01 cm, flow cell
Blank:
Medium
Analysis:
Calculate the percentage of C4H11N5·HCl released at each time point:
Result = [(AU/AS) × CS × (V VS) + (C1 × VS) + (C2 × VS) + (C3 × VS) + (C4 × VS)] × 100/L
VS) + (C1 × VS) + (C2 × VS) + (C3 × VS) + (C4 × VS)] × 100/L| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = initial volume of Medium in the vessel (mL) |
| VS | = | = volume withdrawn from the vessel for previous samplings (mL) |
| C1 | = | = concentration of metformin hydrochloride in Medium determined at the first time point (mg/mL) |
| C2 | = | = concentration of metformin hydrochloride in Medium determined at the second time point (mg/mL) |
| C3 | = | = concentration of metformin hydrochloride in Medium determined at the third time point (mg/mL) |
| C4 | = | = concentration of metformin hydrochloride in Medium determined at fourth time point (mg/mL) |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
For Tablets Labeled to Contain 500 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 20%–40% |
| 5 | 45%–65% |
| 12 | 70%–90% |
| 20 | NLT 85% |
For Tablets Labeled to Contain 750 mg
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 20%–45% |
| 4 | 45%–70% |
| 10 | 70%–95% |
| 24 | NLT 85% |
Test 10:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 10.
Medium:
0.05 M phosphate buffer (prepared by dissolving 6.8 g of potassium dihydrogen phosphate in 250 mL of water, adding 77 mL of 0.2 N sodium hydroxide and 500 mL of water, adjusting with 2 N sodium hydroxide or 2 N hydrochloric acid to a pH 6.8, and diluting with water to 1000 mL), pH 6.8; 1000 mL
Apparatus 1:
100 rpm for Tablets labeled to contain 750 mg
Apparatus 2:
100 rpm for Tablets labeled to contain 500 mg
Times:
1, 3, and 10 h
Standard solution:
L/100,000 mg/mL of USP Metformin Hydrochloride RS in Medium, where L is the Tablet label claim in mg. This solution is stable for 72 h at room temperature.
Sample solution:
At the times specified, withdraw 10 mL of the solution under test and replace with 10 mL of Medium previously equilibrated at 37.0 ± 0.5. Centrifuge at 2500 rpm for 10 min. Dilute a portion of the supernatant with Medium to obtain a theoretical concentration of L/100,000 mg/mL, where L is the Tablet label claim in mg.
. Centrifuge at 2500 rpm for 10 min. Dilute a portion of the supernatant with Medium to obtain a theoretical concentration of L/100,000 mg/mL, where L is the Tablet label claim in mg.
Detector:
UV 233 nm
Path length:
1 cm
Blank:
Medium
Analysis:
Calculate the concentration (mg/mL) of metformin hydrochloride (Ci) at each time point:
Ci = (AU/AS) × CS
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
Calculate the cumulative percentage of metformin hydrochloride dissolved (Qi) at each time point (i):
At i = 1:
Q1 = (C1 × V/L) × 100
At i = 3:
Q3 = [C3(V VS) + (C1 × VS)] × 100/L
VS) + (C1 × VS)] × 100/LAt i = 10:
Q10 = [C10(V 2VS) + (C1 + C3)VS] × 100/L
2VS) + (C1 + C3)VS] × 100/L| V | = | = initial volume of Medium, 1000 mL |
| VS | = | = sampling volume, 10 mL |
| L | = | = label claim (mg/Tablet) |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 25%–45% |
| 3 | 50%–70% |
| 10 | NLT 85% |
Test 11:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 11.
Medium:
pH 6.8 phosphate buffer; 1000 mL
Apparatus 1:
100 rpm for Tablets labeled to contain 750 mg
Apparatus 2:
100 rpm for Tablets labeled to contain 500 mg
Times:
1, 3, and 10 h
Standard solution:
7.5 µg/mL of USP Metformin Hydrochloride RS in Medium
Sample solution:
At the times specified, withdraw 10 mL of the solution under test, and pass it through a suitable filter of 0.45-µm pore size, discarding the first 3 mL. Dilute 3.0 mL of the filtrate with Medium to 200 mL. For Tablets labeled to contain 750 mg, dilute 2.0 mL of the filtrate with Medium to 200 mL. Replace the volume of Medium taken with the same volume of Medium preheated at 37.0 ± 0.5.
.
Detector:
UV 232 nm
Path length:
1 cm
Blank:
Medium
Calculate the percentage of metformin hydrochloride dissolved at each time point:
Qi = (AU/AS) × (CS/L) × V × D × 100
At 1 h:
Result = Q1
At 3 h:
Result = Q3 + [(Q1 × 10)/V]
At 10 h:
Result = Q10 + {[(Q1 × 10)/V] + [(Q3 × 10)/V]}
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 1000 mL |
| D | = | = dilution factor of the Sample solution |
Tolerances:
The percentages of the labeled amount of C4H11N5·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 25%–45% |
| 3 | 50%–70% |
| 10 | NLT 80% |
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Mobile phase, Sample solution, and Chromatographic system:
Prepare as directed in Assay.
Analysis:
From the chromatogram of the Sample solution obtained in Assay, calculate the percentage of each impurity in portion of Tablets taken:
Result = (rU/rT) × 100
| rU | = | = peak response for each impurity |
| rT | = | = sum of all the peak responses |
Acceptance criteria
Individual impurities:
NMT 0.1%
Total impurities:
NMT 0.6%
[Note—Disregard any peak less than 0.05%, and disregard any peak observed in blank. ]
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed, light-resistant containers, and 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 11
11
USP Metformin Hydrochloride RS 
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USP Metformin Related Compound B RS
1-Methylbiguanide hydrochloride.
C3H9N5HCl 151.60
1-Methylbiguanide hydrochloride.
C3H9N5HCl 151.60
USP Metformin Related Compound C RS
N,N-Dimethyl-[1,3,5]triazine-2,4,6-triamine.
C5H10N6 154.17
N,N-Dimethyl-[1,3,5]triazine-2,4,6-triamine.
C5H10N6 154.17
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 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3831
Pharmacopeial Forum: Volume No. 35(1) Page 76