Bupropion Hydrochloride Extended-Release Tablets
» Bupropion Hydrochloride Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of bupropion hydrochloride (C13H18ClNO·HCl).
Packaging and storage— Preserve in well-closed containers.
Labeling— When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
Identification—
A: Infrared Absorption 197K
Test specimen— Crush 1 Tablet using a mortar and pestle. Prepare an approximate 1% (w/w) dispersion of the sample in potassium bromide: the Test specimen shows strong bands at about 1690, 1560, and 1240 cm–1 and a weaker band at about 740 cm–1 similar to the reference preparation.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
for products labeled for dosing every 12 hours—
test 1
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Times: 1, 4, and 8 hours.
Procedure— Determine the amount of C13H18ClNO·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 C13H18ClNO·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 (prepared by transferring about 50 mL of concentrated hydrochloric acid to 6000 mL of water, adding about 18 g of sodium hydroxide, mixing, and adjusting with either diluted sodium hydroxide or hydrochloric acid to a pH of 1.5 ± 0.05); 900 mL, deaerated.
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 C13H18ClNO·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 C13H18ClNO·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%
test 5— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Medium and Procedure— Proceed as directed for Test 1.
Apparatus— Proceed as directed for Test 1, except to use a 0.5-cm cell.
Times: 1, 3, and 6 hours.
Tolerances— The percentages of the labeled amount of C13H18ClNO·HCl dissolved at the times specified conform to Acceptance Table 2.
Time (hours) Amount dissolved
1 between 35% and 55%
3 between 65% and 85%
6 not less than 80%
for products labeled for dosing every 24 hours—
test 4 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium: 0.1 N hydrochloric acid; 900 mL, deaerated.
Apparatus 1: 75 rpm.
Time: 2, 4, 8, and 16 hours.
Procedure— Determine the amount of C13H18ClNO·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 252 nm, using a 1.0-mm 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 C13H18ClNO·HCl dissolved at the times specified conform to Acceptance Table 2.
Time (hours) Amount dissolved
2 not more than 20%
4 between 20% and 45%
8 between 65% and 90%
16 not less than 80%
test 6 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.
Medium and Apparatus: Proceed as directed for Test 4.
Times: 1, 2, 4, 8, and 12 hours.
Procedure— Determine the amount of C13H18ClNO·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 C13H18ClNO·HCl dissolved at the times specified conform to Acceptance Table 2.
Time (hours) Amount dissolved
1 between 15% and 35%
2 between 25% and 50%
4 between 40% and 65%
8 between 65% and 90%
12 not less than 80%
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 Dissolution, except to use a 0.5-cm cell, taking into account the extent of dilution.
Related compounds—
Solution A, Solution B, Mobile phase, System suitability solution 1, System suitability solution 2, and Chromatographic system Proceed as directed in the Assay.
Standard solution— Use the Standard preparation, prepared as directed in the Assay.
Test solution— Use the Assay preparation.
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
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 (C13H18ClNO·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.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Senior Scientist
1-301-816-8330
(MDPP05) Monograph Development-Psychiatrics and Psychoactives
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
711 Margareth R.C. Marques, Ph.D.
Senior Scientist
1-301-816-8106
(BPC05) Biopharmaceutics05
USP32–NF27 Page 1723
Pharmacopeial Forum: Volume No. 34(3) Page 570
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.