Drug release 
724
—
TEST 1—
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Times:
1, 4, and 8 hours.
Procedure—
Determine the amount of C
13H
18ClNO·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 298 nm, using a 1.0-cm cell, 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 Bupropion Hydrochloride RS in the same
Medium.
Tolerances—
The percentages of the labeled amount of C
13H
18ClNO·HCl dissolved at the times specified conform to
Acceptance Table 1 724.
| Time (hours) |
 Amount dissolved |
| 1 |
between 25% and 45% |
| 4 |
between 60% and 85% |
| 8 |
not less than 80% |
TEST 2—
If the product complies with this test, the labeling indicates that it meets USP
Drug Release Test 2.
Medium:
0.1 N hydrochloric acid, pH 1.5; 900 mL.
Apparatus 1:
50 rpm.
Times:
1, 2, 4, and 6 hours.
Determine the percentages of the labeled amount of C13H18ClNO·HCl dissolved by employing the following method.
Buffer solution—
Dissolve 3.45 g of monobasic sodium phosphate monohydrate in 996 mL of water, add 4.0 mL of triethylamine, and mix. Adjust with phosphoric acid to a pH of 2.80 ± 0.05.
Mobile phase—
Prepare a filtered and degassed mixture of
Buffer solution and methanol (65:35). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard solution—
Dissolve an accurately weighed quantity of
USP Bupropion Hydrochloride RS in
Medium, and dilute quantitatively, and stepwise if necessary, with
Medium to obtain a solution having a known concentration similar to the one expected in the
Test solution.
Test solution—
Use portions of the solution under test, and pass through a 0.45-µm nylon filter.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 298-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the
Standard solution, and record the peak responses as directed for
Procedure: the column efficiency is not less than 2000 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of bupropion hydrochloride dissolved at each time point.
Tolerances—
The percentages of the labeled amount of C
13H
18ClNO·HCl dissolved at the times specified conform to
Acceptance Table 1 724.
| Time (hours) |
Amount dissolved |
| 1 |
between 25% and 50% |
| 2 |
between 40% and 65% |
| 4 |
between 65% and 90% |
| 6 |
not less than 80% |
TEST 3—
If the product complies with this test, the labeling indicates that it meets USP
Drug Release Test 3.
Medium, Apparatus, and Procedure—
Proceed as directed for Test 1, except to use the wavelength at about 250 nm.
Times:
1, 2, 4, and 6 hours.
Tolerances—
The percentages of the labeled amount of C
13H
18ClNO·HCl dissolved at the times specified conform to
Acceptance Table 1 724.
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 55% |
| 2 |
between 50% and 75% |
| 4 |
between 70% and 90% |
| 6 |
not less than 80% |
Dissolution 711—
TEST 1—
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Times:
1, 4, and 8 hours.
Procedure—
Determine the amount of C
13H
18ClNO·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 298 nm, using a 1.0-cm cell, 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 Bupropion Hydrochloride RS in the same
Medium.
Tolerances—
The percentages of the labeled amount of C
13H
18ClNO·HCl dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 25% and 45% |
| 4 |
between 60% and 85% |
| 8 |
not less than 80% |
TEST 2—
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 2.
Medium:
0.1 N hydrochloric acid, pH 1.5; 900 mL.
Apparatus 1:
50 rpm.
Times:
1, 2, 4, and 6 hours.
Determine the percentages of the labeled amount of C13H18ClNO·HCl dissolved by employing the following method.
Buffer solution—
Dissolve 3.45 g of sodium phosphate monobasic monohydrate in 996 mL of water, add 4.0 mL of triethylamine, and mix. Adjust with phosphoric acid to a pH of 2.80 ± 0.05.
Mobile phase—
Prepare a filtered and degassed mixture of
Buffer solution and methanol (65:35). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard solution—
Dissolve an accurately weighed quantity of
USP Bupropion Hydrochloride RS in
Medium, and dilute quantitatively, and stepwise if necessary, with
Medium to obtain a solution having a known concentration similar to the one expected in the
Test solution.
Test solution—
Use portions of the solution under test, and pass through a 0.45-µm nylon filter.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 298-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the
Standard solution, and record the peak responses as directed for
Procedure: the column efficiency is not less than 2000 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of bupropion hydrochloride dissolved at each time point.
Tolerances—
The percentages of the labeled amount of C
13H
18ClNO·HCl dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 25% and 50% |
| 2 |
between 40% and 65% |
| 4 |
between 65% and 90% |
| 6 |
not less than 80% |
TEST 3—
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 3.
Medium, Apparatus, and Procedure—
Proceed as directed for Test 1, except using the wavelength of about 250 nm.
Times:
1, 2, 4, and 6 hours.
Tolerances:
The percentages of the labeled amount of C
13H
18ClNO·HCl dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 55% |
| 2 |
between 50% and 75% |
| 4 |
between 70% and 90% |
| 6 |
not less than 80% |
(Official April 1, 2006)
Uniformity of dosage units 905:
meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Standard solution—
Dissolve an accurately weighed quantity of
USP Bupropion Hydrochloride RS in water to obtain a solution having a known concentration of about 0.33 mg of bupropion hydrochloride per mL.
Test solution—
Transfer 1 Tablet to a suitable homogenizer vessel containing an accurately measured volume of water to obtain a concentration of about 0.33 mg of bupropion hydrochloride per mL. Immediately homogenize the sample using single 30-second pulses each at 5000, 10,000, and 15,000 rpm, and follow by two pulses each at 20,000 rpm. After the homogenate has settled, mix at 5000 rpm for an additional 30 seconds. Pass a portion of the solution through a nylon filter having a 0.45-µm porosity, discarding the first 4 mL of the filtrate.
Procedure—
Proceed as directed in the test for Drug release, except to use a 0.5-cm cell, taking into account the extent of dilution.
Change to read:
Related compounds—
Solution A, Solution B, Mobile phase, System suitability solution 1, System suitability solution 2, 
and Chromatographic systemUSP29 —
Proceed as directed in the
Assay.
Standard solution—
Use the
Standard preparation, prepared as directed in the
Assay.USP29
Test solution—
Use the Assay preparation.
USP29
Procedure—
Separately inject equal volumes (about 5 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks.
Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
100(C/D)F(ri / rS)
in which
C is the concentration, in mg per mL, of bupropion hydrochloride in the
Standard solution; F is the relative response factor for each impurity (see the accompanying table);
D is the concentration, in mg per mL, of bupropion hydrochloride in the
Test solution, based on the number of Tablets taken, the labeled quantity per Tablet, and the extent of dilution;
ri is the peak response for each impurity obtained from the
Test solution; and
rS is the peak response for bupropion hydrochloride obtained from the
Standard solution. See the accompanying table for limits of individual impurities based upon Tablet strength.
|
|
|
Limit (%) |
| Compound |
Relative
Retention Time |
F |
100 mg or less |
150 mg or
greater |
| 2-Amino-1-(3-chlorophenyl)-1-propanone |
about 0.38 |
0.80 |
0.3 |
0.3 |
(3S,5S,6S)-6-(3-Chlorophenyl)-6-hydroxy-5-methyl-3-
thiomorpholine carboxylic acid |
about 0.56 |
0.86 |
1.0 |
1.5 |
(3S,5R,6R)-6-(3-Chlorophenyl)-6-hydroxy-5-methyl-3-
thiomorpholine carboxylic acid |
about 0.78 |
0.88 |
0.5 |
0.4 |
| Bupropion |
1.0 |
— |
— |
— |
| Bupropion related compound F |
about 1.71 |
0.55 |
1.2 |
2.3 |
| Bupropion related compound C |
about 1.75 |
0.59 |
0.3 |
0.3 |
| m-Chlorobenzoic acid |
about 1.80 |
0.24 |
0.3 |
0.3 |
| Bupropion related compound E |
about 2.25 |
1.00 |
0.4 |
0.4 |
| Any unspecified impurity |
— |
1.00 |
0.2 |
0.2 |
| Total impurities |
— |
— |
3.2 |
3.3 |
USP29
Assay—
Solution A—
Prepare a filtered and degassed mixture of water, acetonitrile, and trifluoroacetic acid (90:10:0.04).
Solution B—
Prepare a filtered and degassed mixture of acetonitrile, water, and trifluoroacetic acid (95:5:0.03).
Mobile phase—
Use variable mixtures of
Solution A and
Solution B as directed for
Chromatographic system. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
System suitability solution 1—
Prepare separate solutions containing accurately weighed quantities of
USP Bupropion Hydrochloride Related Compound C RS and USP Bupropion Hydrochloride Related Compound F RS in methanol to obtain solutions having concentrations of about 0.20 mg per mL. Transfer accurately measured volumes of these solutions to a suitable flask, and dilute with a mixture of 0.001 N hydrochloric acid and methanol (80:20) to obtain a solution having a concentration of about 0.0018 mg of
USP Bupropion Hydrochloride Related Compound C RS per mL and 0.018 mg of USP Bupropion Hydrochloride Related Compound F RS per mL.
System suitability solution 2—
Prepare a solution containing an accurately weighed quantity of m-chlorobenzoic acid to obtain a solution having a concentration of about 0.09 mg per mL. Dilute an accurately measured volume of this solution with a mixture of 0.001 N hydrochloric acid and methanol (80:20) to obtain a solution having a concentration of about 0.0018 mg of m-chlorobenzoic acid per mL.
Standard preparation—
Dissolve an accurately weighed quantity of
USP Bupropion Hydrochloride RS in a mixture of 0.001 N hydrochloric acid and methanol (80:20) to obtain a solution having a known concentration of about 0.6 mg of bupropion hydrochloride per mL.
Assay preparation—
Transfer a number of Tablets to a suitable homogenizer vessel containing an accurately measured volume of methanol to obtain a concentration of about 3.0 mg of bupropion hydrochloride per mL. Immediately homogenize the sample for 30 seconds at 20,000 rpm. Allow to extract for 3 minutes, and follow by two additional 10-second pulses, each at 20,000 rpm, pausing 3 minutes between these pulses to ensure complete extraction. Pass a portion of the solution through a nylon filter having a 0.45-µm porosity, discarding the first 2 to 4 mL of the filtrate. Pipet 10.0 mL of the filtrate into a 50-mL volumetric flask, and add about 25 mL of 0.001 N hydrochloric acid. Allow to cool to room temperature, and dilute with 0.001 N hydrochloric acid to volume.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 226-nm detector and a 4.6-mm × 10-cm column that contains 3.5-µm packing L1. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.
Time
(minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
| 0 |
90 |
10 |
equilibration |
| 0–3.4 |
90®87 |
10®13 |
linear gradient |
| 3.4–10.0 |
87®15 |
13®85 |
linear gradient |
| 10.0–10.1 |
15®0 |
85®100 |
linear gradient |
| 10.1–13.0 |
0 |
100 |
isocratic |
| 13.0–13.2 |
0®90 |
100®10 |
linear gradient |
| 13.2–19.0 |
90 |
10 |
isocratic |
Chromatograph
System suitability solution 1, System suitability solution 2, and the
Standard preparation, and record the peak areas as directed for
Procedure: the resolution,
R, between bupropion hydrochloride related compound C and bupropion hydrochloride related compound F is not less than 1.5; the relative response factor for
System suitability solution 2 is between 0.22 and 0.26 when calculated using the peak obtained in the
Standard preparation; the tailing factor is not more than 1.9; and the relative standard deviation for replicate injections of the
Standard preparation is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 5 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the amount, in mg, of bupropion hydrochloride (C
13H
18ClNO·HCl) in the portion of Tablets taken by the formula:
(TC/D)(rU / rS)
in which
T is the labeled quantity, in mg, of bupropion hydrochloride in the Tablet;
C is the concentration, in mg per mL, of
USP Bupropion Hydrochloride RS in the
Standard preparation; D is the concentration, in mg per mL, of bupropion hydrochloride in the
Assay preparation, based upon the labeled quantity per Tablet and the extent of dilution; and
rU and
rS are the peak responses for bupropion hydrochloride obtained from the
Assay preparation and the
Standard preparation, respectively.
