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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volume withdrawn from the vessel for previous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.
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
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:
Figure 1
Figure 2