Revision Bulletin

Official September 1, 2010 Metformin 1

Relative standard deviation: NMT 1.5% for the

Metformin Hydrochloride Extended-
.

metformin peak and NMT 10% for each of the peaks

Release Tablets due to metformin related compound B and metformin
related compound C
DEFINITION Analysis
Metformin Hydrochloride Extended-Release Tablets contain NLT Samples: Standard solution and Sample solution
90.0% and NMT 110.0% of the labeled amount of Calculate the percentage of C4H11N5 · HCl in the portion of
metformin hydrochloride (C4H11N5 · HCl). Tablets taken:

IDENTIFICATION Result = (rU/rS) × (CS/CU) × 100

• The retention time of the major peak from the Sample solu-
tion corresponds to that from the Standard solution, as ob- rU = peak response from the Sample solution
tained in the Assay. rS = peak response from the Standard solution
CS = concentration of USP Metformin Hydrochloride
ASSAY RS in the Standard solution (mg/mL)
• PROCEDURE CU = nominal concentration of metformin hydrochlo-
Buffer solution: 0.5 g/L of sodium heptanesulfonate and 0.5 ride in the Sample solution
g/L of sodium chloride in water. Prior to final dilution, adjust Acceptance criteria: 90.0%–110.0%
with 0.06 M phosphoric acid to a pH of 3.85.
Mobile phase: Acetonitrile and Buffer solution (1:9). [NOTE— PERFORMANCE TESTS
To improve the separation, the composition of acetonitrile
and Buffer solution may be changed to 1:19, if necessary.] Change to read:
Diluent: 1.25% solution of acetonitrile in water
Standard solution: (L/4000) mg/mL of USP Metformin Hy- • DISSOLUTION 〈711〉
drochloride RS in Diluent, where L is the labeled quantity, in Test 1
mg, of metformin hydrochloride in each Tablet Medium: pH 6.8 phosphate buffer (6.8 g of monobasic po-
System suitability stock solution: 12.5 µg/mL of each of tassium phosphate in 1000 mL of water; adjust with 0.2 N
USP Metformin Related Compound B RS and USP Metformin sodium hydroxide to a pH of 6.8 ± 0.1); 1000 mL
Related Compound C RS in Diluent Apparatus 1: 100 rpm for Tablets labeled to contain 750
System suitability solution: Dilute 0.5 mL of the System mg
suitability stock solution with the Standard solution to 50 mL. Apparatus 2: 100 rpm for Tablets labeled to contain 500
Sample stock solution: Finely powder NLT 10 Tablets. mg
Transfer powder, equivalent to the average Tablet weight, to Times: 1, 3, and 10 h
a homogenization vessel, and accurately add 500 mL of Detector: UV 232 nm
10% acetonitrile solution. Alternately, homogenize and allow Standard solution: USP Metformin Hydrochloride RS in
to soak until the sample is fully homogenized. [NOTE—A sug- Medium
gested homogenization sequence is as follows. Homogenize Sample solution: Pass a portion of the solution under test
the sample using five pulses, each of 5 s, at about 20,000 through a suitable hydrophilic polyethylene filter of 0.45-
rpm, and allow to soak for 2 min. Repeat these steps two µm pore size. Dilute, if necessary, with Medium to a con-
additional times.] centration similar to the Standard solution.
Sample solution: Pass a portion of the Sample stock solution Analysis: Calculate the percentage of C4H11N5 · HCl re-
through a suitable filter of 0.45-µm pore size, discarding the leased at each time point:
first 3 mL of filtrate. Transfer 25 mL of the filtrate to a 200-
mL volumetric flask, and dilute with water to volume. Result = [(AU/AS) × CS × (V − VS) + (C60 × VS) + (C180 × VS) ×
Chromatographic system 100]/L
(See Chromatography 〈621〉, System Suitability.)
Mode: LC AU = absorbance of the Sample solution
Detector: UV 218 nm AS = absorbance of the Standard solution
Column: 3.9-mm × 30-cm; 10-µm packing L1 CS = concentration of the Standard solution (mg/mL)
Column temperature: 30° V = initial volume of Medium in the vessel (mL)
Flow rate: 1 mL/min VS = volume withdrawn from the vessel for previous
Injection size: 10 µL samplings (mL)
Run time: Until after the elution locus of metformin related C60 = concentration of metformin hydrochloride in Me-
compound C dium determined at 1 h (mg/mL)
System suitability C180 = concentration of metformin hydrochloride in Me-
Sample: System suitability solution dium determined at 3 h (mg/mL)
[NOTE—The relative retention times for metformin related L = label claim (mg/Tablet)
compound B, metformin, and metformin related com- Tolerances: The percentages of the labeled amount of
pound C are 0.86, 1.0, and 2.1–2.3, respectively. C4H11N5 · HCl dissolved at the times specified conform to
Metformin related compound C can have a variable reten- Acceptance Table 2.
tion time. The composition of the Mobile phase may be
changed to 1:19, if it elutes at a relative retention time of Time Amount Dissolved, Amount Dissolved,
less than 2.1.] (h) 500-mg Tablet 750-mg Tablet
Suitability requirements
1 20%–40% 22%–42%
Resolution: NLT 1.5 between peaks due to metformin
related compound B and metformin 3 45%–65% 49%–69%
Tailing factor: NLT 0.8 and NMT 2.0 for the metformin 10 NLT 85% NLT 85%
peak

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 Revision Bulletin
2 Metformin Official September 1, 2010

Test 2: If the product complies with this test, the labeling Test 3: If the product complies with this test, the labeling
indicates that it meets USP Dissolution Test 2. indicates that it meets USP Dissolution Test 3.
Medium: Prepare as directed for Test 1; 1000 mL Medium, Apparatus 1, Apparatus 2, and Analysis: Pro-
Apparatus 2: 100 rpm ceed as directed in Test 1.
Times: 1, 2, 6, and 10 h Times: 1, 2, 5, and 12 h for Tablets labeled to contain 500
Detector: UV 232 nm mg; and 1, 3, and 10 h for Tablets labeled to contain 750
Standard solution: USP Metformin Hydrochloride RS in mg
Medium Detector: UV 232 nm
Sample solution: Pass a portion of the solution under test Standard solution: USP Metformin Hydrochloride RS in
through a suitable polyethylene filter of 0.45-µm pore size. Medium
Dilute, if necessary, with Medium to a concentration that is Sample solution: Pass a portion of the solution under test
similar to the Standard solution. through a suitable hydrophilic polyethylene filter of 0.45-
Analysis: Calculate, in mg/mL, the content of C4H11N5 · µm pore size. Dilute, if necessary, with Medium to a con-
HCl, Ct, in Medium at each time point, t: centration similar to the Standard solution.
Analysis: Calculate the percentage of C4H11N5 · HCl re-
Result = (AU × CS × DU)/AS leased at each time point:
AU = absorbance of the Sample solution •Result = {[(AU/AS) × CS × (V − VS) + (C60 × VS) + (C120 × VS)
CS = concentration of metformin hydrochloride in the + (C300 × VS) + (C720 × VS)] × 100}/L•(RB 2-Nov-2009)
Standard solution (mg/mL)
DU = dilution factor of the solution under test AU =
absorbance of the Sample solution
AS = absorbance of the Standard solution AS =
absorbance of the Standard solution
Calculate the percentage of C4H11N5 · HCl dissolved at each CS =
concentration of the Standard solution (mg/mL)
time point by the following formulas. V =
initial volume of Medium in the vessel (mL)
Percentage dissolved at the first time point (1 h): VS =
volume withdrawn from the vessel for previous
samplings (mL)
Result = (C1 × V × 100)/L C60 = concentration of metformin hydrochloride in Me-
dium determined at 1 h (mg/mL)
C1 = content of metformin hydrochloride in Medium C120 = concentration of metformin hydrochloride in Me-
at the first time interval (mg/mL) dium determined at 2 h (mg/mL)
V = volume of Medium, 1000 mL C300 = concentration of metformin hydrochloride in Me-
L = label claim (mg/Tablet) dium determined at 5 h (mg/mL)
Percentage dissolved at the second time point (2 h): •C720 = concentration of metformin hydrochloride in Me-
dium determined at 12 h (mg/mL)•(RB 2-Nov-2009)
Result = [C2 × (V − SV1) + C1 × SV1 × 100]/L L = label claim (mg/Tablet)
Tolerances: The percentages of the labeled amount of
C2 = content of metformin hydrochloride in Medium C4H11N5 · HCl dissolved at the times specified conform to
at the second time interval (mg/mL) Acceptance Table 2.
V = volume of Medium, 1000 mL
SV1 = volume of the sample withdrawn at 1 h (mL)
C1 = content of metformin hydrochloride in Medium For Tablets Labeled to Contain 500 mg
at 1 h (mg/mL) Time
L = label claim (mg/Tablet) (h) Amount Dissolved
Percentage dissolved at the nth time point: 1 20%–40%
Result = {Cn × [V − (n − 1)VS] + (C1 + C2 + … + Cn−1) × VS × 2 35%–55%
100}/L 5 60%–80%
12 NLT 85%
Cn = content of metformin hydrochloride in Medium
at the nth time interval (mg/mL)
V = volume of Medium, 1000 mL For Tablets Labeled to Contain 750 mg
n = time interval of interest
VS = volume of sample withdrawn at each time inter- Time
val (mL) (h) Amount Dissolved
C = as C1, C2, C3, … Cn–1, the content of metformin 1 22%–42%
hydrochloride in Medium at each time interval 3 49%–69%
(mg/mL) 10 NLT 85%
L = label claim (mg/Tablet)
Tolerances: The percentages of the labeled amount of Test 4: If the product complies with this test, the labeling
C4H11N5 · HCl dissolved at the times specified conform to indicates that it meets USP Dissolution Test 4.
Acceptance Table 2. Medium: Prepare as directed for Test 1; 1000 mL
Apparatus 2: 100 rpm
Time Times: 1, 3, 6, and 10 h
(h) Amount Dissolved Detector: UV 250 nm (shoulder)
1 20%–40%
Standard solution: USP Metformin Hydrochloride RS in
Medium
2 35%–55% Sample solution: Pass a portion of the solution under test
6 65%–85% through a ▲suitable filter of 0.45-µm pore size.▲USP33 Dilute,
10 NLT 85% if necessary, with Medium to a concentration similar to the
Standard solution.

2010 The United States Pharmacopeial Convention All Rights Reserved.

Revision Bulletin
Official September 1, 2010 Metformin 3

Analysis: Calculate, in mg/mL, the content of C4H11N5 · CS = concentration of the Standard solution (mg/mL)
HCl, Ct, in Medium at each time point, t, by the formulas V = initial volume of Medium in the vessel (mL)
specified in Test 2. VS = volume withdrawn from the vessel for previous
Tolerances: The percentages of the labeled amount of samplings (mL)
C4H11N5 · HCl dissolved at the times specified conform to C60 = concentration of metformin hydrochloride in Me-
Acceptance Table 2. dium determined at 1 h (mg/mL)
C180 = concentration of metformin hydrochloride in Me-
Time dium determined at 3 h (mg/mL)
(h) Amount Dissolved C600 = concentration of metformin hydrochloride in Me-
dium determined at 10 h (mg/mL)
1 20%–40%
L = label claim (mg/Tablet)
3 45%–65% Tolerances: The percentages of the labeled amount of
6 65%–85% C4H11N5 · HCl dissolved at the times specified conform to
10 NLT 85% Acceptance Table 2.
Test 5: If the product complies with this test, the labeling
Time Amount Dissolved, Amount Dissolved,
indicates that it meets USP Dissolution Test 5.
(h) 500-mg Tablet 750-mg Tablet
Medium: pH 6.8 phosphate buffer (6.8 g of monobasic po-
tassium phosphate in 1000 mL of water; adjust with 0.2 N 1 20%–40% 20%–40%
sodium hydroxide to a pH of 6.8 ± 0.1); 900 mL, deaerated 3 45%–65% 45%–65%
Apparatus 1: 100 rpm, with the vertical holder described 10 NLT 85% NLT 85%
in Figure 1 and Figure 2
Times: 2, 8, and 16 h Test 7: If the product complies with this test, the labeling
Detector: UV 250 nm indicates that it meets USP Dissolution Test 7.
Standard solution: USP Metformin Hydrochloride RS in Medium: Prepare as directed in Test 1; 1000 mL
Medium Apparatus 1: 100 rpm for Tablets labeled to contain 750
Sample solution: Pass a portion of the solution under test mg
through a ▲suitable filter of 0.45-µm pore size.▲USP33 Dilute, Apparatus 2: 50 rpm, with USP sinker, for Tablets labeled
if necessary, with Medium to a concentration similar to the to contain 500 mg
Standard solution. Times: 1, 3, and 10 h
Analysis: Place a vertical sample holder into each basket Detector: UV 232 nm
(see Figures 1 and 2). Place 1 Tablet inside the sample Standard solution: USP Metformin Hydrochloride RS in
holder, making sure that the Tablets are vertical at the bot- Medium
tom of the baskets. Sample solution: Pass a portion of the solution under test
Calculate, in mg/mL, the content of C4H11N5 · HCl, Ct, in through a suitable filter of 0.45-µm pore size. Dilute, if nec-
Medium at each time point, t, by the formulas specified in essary, with Medium to a concentration similar to the Stan-
Test 2. dard solution.
Tolerances: The percentages of the labeled amount of Analysis: Calculate the percentage of C4H11N5 · HCl re-
C4H11N5 · HCl dissolved at the times specified conform to leased at each time point:
Acceptance Table 2.
Result = {[(AU/AS) × CS × (V − VS) + (C60 × VS) + (C180 × VS) +
(C600 × VS)] × 100}/L
Time Amount Dissolved, Amount Dissolved,
(h) 500-mg Tablet 1000-mg Tablet AU = absorbance of the Sample solution
2 NMT 30% NMT 30% AS = absorbance of the Standard solution
8 60%–85% 65%–90% CS = concentration of the Standard solution (mg/mL)
16 NLT 90% NLT 90% V = initial volume of Medium in the vessel (mL)
VS = volume withdrawn from the vessel for previous
Test 6: If the product complies with this test, the labeling samplings (mL)
indicates that it meets USP Dissolution Test 6. C60 = concentration of metformin hydrochloride in Me-
Medium: pH 6.8 phosphate buffer (6.8 g of monobasic po- dium determined at 1 h (mg/mL)
tassium phosphate in 1000 mL of water; adjust with 0.2 N C180 = concentration of metformin hydrochloride in Me-
sodium hydroxide to a pH of 6.8 ± 0.05); 1000 mL, dium determined at 3 h (mg/mL)
deaerated C600 = concentration of metformin hydrochloride in Me-
Apparatus 2: 100 rpm, with USP sinker, if necessary dium determined at 10 h (mg/mL)
Detector: UV 233 nm L = label claim (mg/Tablet)
Standard solution: USP Metformin Hydrochloride RS in Tolerances: The percentages of the labeled amount of
Medium C4H11N5 · HCl dissolved at the times specified conform to
Sample solution: Pass a portion of the solution under test Acceptance Table 2.
through a suitable hydrophilic polyethylene filter of 0.45-
µm pore size. Dilute, if necessary, with Medium to a con- Time Amount Dissolved, Amount Dissolved,
centration similar to the Standard solution. (h) 500-mg Tablet 750-mg Tablet
Analysis: Calculate the percentage of C4H11N5 · HCl re- 1 20%–40% 20%–40%
leased at each time point:
3 45%–65% 40%–60%
Result = {[(AU/AS) × CS × (V − VS) + (C60 × VS) + (C180 × VS) + 10 NLT 85% NLT 80%
(C600 × VS)] × 100}/L
Test 8: If the product complies with this test, the labeling
AU = absorbance of the Sample solution indicates that it meets USP Dissolution Test 8.
AS = absorbance of the Standard solution

2010 The United States Pharmacopeial Convention All Rights Reserved.

 Revision Bulletin
4 Metformin Official September 1, 2010

Medium: Prepare as directed in Test 1; 1000 mL AU =

absorbance of the Sample solution
Apparatus 1: 100 rpm for Tablets labeled to contain 750 AS =
absorbance of the Standard solution
mg CS =
concentration of the Standard solution (mg/mL)
Apparatus 2: 100 rpm, with sinker, for Tablets labeled to V =
initial volume of Medium in the vessel (mL)
contain 500 mg VS =
volume withdrawn from the vessel for previous
Times: 1, 2, 6, and 10 h samplings (mL)
Detector: UV 232 nm C1 = concentration of metformin hydrochloride in Me-
Standard solution: USP Metformin Hydrochloride RS in dium determined at the first time point
Medium (mg/mL)
Sample solution: Pass a portion of the solution under test C2 = concentration of metformin hydrochloride in Me-
through a suitable filter of 0.45-µm pore size. Dilute, if nec- dium determined at the second time point
essary, with Medium to a concentration similar to the Stan- (mg/mL)
dard solution. C3 = concentration of metformin hydrochloride in Me-
Analysis: Calculate the percentage of C4H11N5 · HCl re- dium determined at the third time point
leased at each time point: (mg/mL)
C4 = concentration of metformin hydrochloride in Me-
Result = {[(AU/AS) × CS × (V − VS) + (C60 × VS) + (C120 × VS) + dium determined at the fourth time point
(C360 × VS) + (C600 × VS)] × 100}/L (mg/mL)
L = label claim (mg/Tablet)
AU = absorbance of the Sample solution Tolerances: The percentages of the labeled amount of
AS = absorbance of the Standard solution C4H11N5 · HCl dissolved at the times specified conform to
CS = concentration of the Standard solution (mg/mL) Acceptance Table 2.
V = initial volume of Medium in the vessel (mL)
VS = volume withdrawn from the vessel for previous
For Tablets Labeled to Contain 500 mg
samplings (mL)
C60 = concentration of metformin hydrochloride in Me- Time
dium determined at 1 h (mg/mL) (h) Amount Dissolved
C120 = concentration of metformin hydrochloride in Me- 1 20%–40%
dium determined at 2 h (mg/mL) 5 45%–65%
C360 = concentration of metformin hydrochloride in Me-
12 70%–90%
dium determined at 6 h (mg/mL)
C600 = concentration of metformin hydrochloride in Me- 20 NLT 85%
dium determined at 10 h (mg/mL)
L = label claim (mg/Tablet)
Tolerances: The percentages of the labeled amount of For Tablets Labeled to Contain 750 mg
C4H11N5 · HCl dissolved at the times specified conform to Time
Acceptance Table 2. (h) Amount Dissolved
1 20%–45%
Time Amount Dissolved, Amount Dissolved, 4 45%–70%
(h) 500-mg Tablet 750-mg Tablet
10 70%–95%
1 20%–40% 20%–40%
24 NLT 85%
2 30%–50% 35%–55%
6 65%–85% 75%–95% •Test 10: If the product complies with this test, the labeling
10 NLT 85% NLT 85% indicates that it meets USP Dissolution Test 10.
Medium: 0.05 M phosphate buffer (prepared by dissolving
Test 9: If the product complies with this test, the labeling 6.8 g of potassium dihydrogen phosphate in 250 mL of
indicates that it meets USP Dissolution Test 9. water, adding 77 mL of 0.2 N sodium hydroxide and 500
Medium: 0.05 M phosphate buffer, pH 6.8; 1000 mL mL of water, adjusting with 2 N sodium hydroxide or 2 N
•Apparatus 1: 100 rpm, for Tablets labeled to contain hydrochloric acid to a pH 6.8, and diluting with water to
750 mg• (RB 1-Mar-2010) 1000 mL), pH 6.8; 1000 mL
Apparatus 2: 100 rpm, •for Tablets labeled to contain 500 Apparatus 1: 100 rpm for Tablets labeled to contain 750
mg•(RB 1-Mar-2010) mg
Times: 1, 5, 12, and 20 h for Tablets labeled to contain Apparatus 2: 100 rpm for Tablets labeled to contain 500
500 mg; and 1, 4, 10, and 24 h for Tablets labeled to mg
contain 750 mg Times: 1, 3, and 10 h
Standard solution: 0.5 mg/mL of USP Metformin Hydro- Standard solution: L/100,000 mg/mL of USP Metformin
chloride RS in Medium Hydrochloride RS in Medium, where L is the Tablet label
Sample solution: Pass a portion of the solution under test claim in mg. This solution is stable for 72 h at room
through a suitable filter of 0.45-µm pore size. temperature.
Detector: UV 232 nm Sample solution: At the times specified, withdraw 10 mL
Path length: 0.01 cm, flow cell of the solution under test and replace with 10 mL of Me-
Blank: Medium dium previously equilibrated at 37.0 ± 0.5°. Centrifuge at
Analysis: Calculate the percentage of C4H11N5 · HCl re- 2500 rpm for 10 min. Dilute a portion of the supernatant
leased at each time point: with Medium to obtain a theoretical concentration of L/
100,000 mg/mL, where L is the Tablet label claim in mg.
Result = [(AU/AS) × CS × (V − VS) + (C1 × VS) + (C2 × VS) + (C3
× VS) + (C4 × VS)] × 100/L

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Revision Bulletin
Official September 1, 2010 Metformin 5

Detector: UV 233 nm At 1 h:
Path length: 1 cm
Blank: Medium Result = Q1
Analysis: Calculate the concentration (mg/mL) of
metformin hydrochloride (Ci) at each time point: At 3 h:

Ci = (AU/AS) × CS Result = Q3 + [(Q1 × 10)/V]

AU = absorbance of the Sample solution At 10 h:

AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL) Result = Q10 + {[(Q1 × 10)/V] + [(Q3 × 10)/V]}
Calculate the cumulative percentage of metformin hydro-
chloride dissolved (Qi) at each time point (i): AU = absorbance of the Sample solution
At i = 1: AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL)
Q1 = (C1 × V/L) × 100 L = label claim (mg/Tablet)
V = volume of Medium, 1000 mL
At i = 3: D = dilution factor of the Sample solution
Tolerances: The percentages of the labeled amount of
Q3 = [C3(V − VS) + (C1 × VS)] × 100/L C4H11N5 · HCl dissolved at the times specified conform to
Acceptance Table 2.
At i = 10:
Time
Q10 = [C10(V − 2VS) + (C1 + C3)VS] × 100/L (h) Amount Dissolved
V = initial volume of Medium, 1000 mL 1 25%–45%
VS = sampling volume, 10 mL 3 50%–70%
L = label claim (mg/Tablet) 10 NLT 80%
Tolerances: The percentages of the labeled amount of
C4H11N5 · HCl dissolved at the times specified conform to • (RB 1-Sep-2010)
Acceptance Table 2. • UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the requirements
IMPURITIES
Time Organic Impurities
(h) Amount Dissolved • PROCEDURE
1 25%–45% Mobile phase, Sample solution, and Chromatographic
3 50%–70% system: Prepare as directed in the Assay.
10 NLT 85% Analysis: From the chromatogram of the Sample solution
obtained in the Assay, calculate the percentage of each im-
• (RB 2-Nov-2009) purity in the portion of Tablets taken:
• Test 11: If the product complies with this test, the labeling
indicates that it meets USP Dissolution Test 11. Result = (rU/rT) × 100
Medium: pH 6.8 phosphate buffer; 1000 mL
Apparatus 1: 100 rpm for Tablets labeled to contain 750 rU = peak response for each impurity
mg rT = sum of all the peak responses
Apparatus 2: 100 rpm for Tablets labeled to contain 500 Acceptance criteria
mg Individual impurities: NMT 0.1%
Times: 1, 3, and 10 h Total impurities: NMT 0.6%
Standard solution: 7.5 µg/mL of USP Metformin Hydro- [NOTE—Disregard any peak less than 0.05%, and disre-
chloride RS in Medium gard any peak observed in the blank.]
Sample solution: At the times specified, withdraw 10 mL
of the solution under test, and pass it through a suitable ADDITIONAL REQUIREMENTS
filter of 0.45-µm pore size, discarding the first 3 mL. Dilute • PACKAGING AND STORAGE: Preserve in well-closed, light-resis-
3.0 mL of the filtrate with Medium to 200 mL. For Tablets tant containers, and store at controlled room temperature.
labeled to contain 750 mg, dilute 2.0 mL of the filtrate • LABELING: When more than one dissolution test is given, the
with Medium to 200 mL. Replace the volume of Medium labeling states the Dissolution Test used only if Test 1 is not
taken with the same volume of Medium preheated at 37.0 used.
± 0.5°. • USP REFERENCE STANDARDS 〈11〉
Detector: UV 232 nm USP Metformin Hydrochloride RS
Path length: 1 cm USP Metformin Related Compound B RS
Blank: Medium USP Metformin Related Compound C RS
Calculate the percentage of metformin hydrochloride dis-
solved at each time point:
Qi = (AU/AS) × (CS/L) × V × D × 100

2010 The United States Pharmacopeial Convention All Rights Reserved.

 Revision Bulletin
6 Metformin Official September 1, 2010

Figure 1

2010 The United States Pharmacopeial Convention All Rights Reserved.

Revision Bulletin
Official September 1, 2010 Metformin 7

Figure 2

2010 The United States Pharmacopeial Convention All Rights Reserved.