Bupropion Hydrochloride Prolonged-release Tablets
Bupropion Hydrochloride Sustained-release Tablets; Bupropion Hydrochloride Extended-release Tablets
“Bupropion Hydrochloride Prolonged-release Tablets manufactured by different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable, as the dissolution profile of the products of different manufacture may not be the same”
Bupropion Hydrochloride Prolonged-release Tablets contains not less than 90.0 per cent and not more than 110.0 per cent of the labeled amount of bupropion hydrochloride, C13H18ClNO,HCl.
Usual strengths. 100 mg; 150 mg; 300 mg.
Identification
- Determine by infrared absorption spectophotometry (2.4.6). Compare the spectrum with that obtained withbupropion hydrochloride RSor with the reference spectrum of bupropion hydrochloride.
- In the Assay, the principal peak in the chromatogram obtained with the test solution (a) or (b) corresponds to the peak in the chromatogram obtained with reference solution (g).
Tests
Dissolution (2.5.2). Complies with the test stated under Tablets.
Related substances. Determine by liquid chromatography (2.4.14).
Solvent mixture (a). a mixture of 20 volumes of methanol and 80 volumes of 0.001 M hydrochloric acid.
Solvent mixture (b). a mixture of a 80 volumes of buffer solution prepared by dissolving 100 g of anhydrous disodium hydrogen phosphate in 1000 ml of water. Add 50 ml of orthophosphoric acid, ultrasound and mix. Adjust the pH 3.0 with orthophosphoric acid and 20 volumes of methanol.
Test solution(a). Disperse a quantity of the powder tablets, containing 300 mg of Bupropion Hydrochloride in 100.0 ml of methanol with the aid of ultrasound and centrifuge at 20000 rpm for about 3 minutes. Filter, discarding the first few ml of filtrate. Dilute 10.0 ml of this solution to 50.0 ml with 0.001M hydrochloric acid.
NOTE —Alternatively,the sample can be prepared as follows.
Test solution (b). Weigh and powder 20 tablets. Weigh a quantity of powder containing 300 mg of Bupropion Hydrochloride in 75 ml of solvent mixture (b).Stir for 30 minutes and ultrasound for 15 minutes and dilute to 100.0 ml with the same solvent and centrifuge, use the supernatant. Dilute 10.0 ml of this solution to 50.0 ml with solvent mixture (b).
Reference solution (a). A 0.002 per cent w/v solution of bupropion hydrochloride C RS [1-(3-chlorophenyl)-2-hydroxypropan-1-one], bupropion hydrochloride F RS [1-(3-chlorophenyl)-1-hydroxypropan-2-one] and 0.0012 per cent w/v solution of 3-chlorobenzoic acid RS in methanol.
Reference solution (b). Dilute 10.0 ml of reference solution (a) to 100.0 ml with solvent mixture (a).
Reference solution (c). 0.0012 per cent w/v solution of 3-chlorobenzoic acid RS in methanol.
Reference solution (d). Dilute 10.0 ml of reference solution (c) to 100.0 ml with solvent mixture (a).
Reference solution (e). 0.00012 per cent w/v solution of bupropion hydrochloride RS in the solvent mixture (a).
Chromatographic system
– a stainless steel column 10 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (3.5 µm),
– column temperature: 40°,
– mobile phase: A. a mixture of 10 volumes of acetonitrile, 0.04 volume of trifluoroacetic acid and 90 volumes of water,
- a mixture of 95 volumes of acetonitrile, 0.03 volume of trifluoroacetic acid and 5 volumes of water,
– a gradient programme using the conditions given below,
– flow rate: 1.5 ml per minute,
– spectrophotometer set at 226 ± 2 nm so that the relative response factor requirement is met.
[ Note- The peak responses of the compounds of interest are very sensitive tochange in the detection wavelength],
– injection volume: 5 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 90 10
3.4 87 13
10.0 15 85
10.1 0 100
13.0 0 100
13.2 90 10
19.0 90 10
Name Relative Correction
retention time factor
Bupropion amine1 0.38 0.83
S,S,S-Thiomorpholine derivative2 0.56 0.90
S,R,R-Thiomorpholine derivative3 0.78 0.90
Bupropion 1.0 ---
Bupropion related compound F 1.71 0.55
Bupropion related compound C 1.75 0.58
3-Chlorobenzoic acid 1.80 ---
Bupropion dione derivative4 2.25 1.0
Unknown impurity --- 1.0
12-Amino-1-(3-chlorophenyl)-1-propanone,
2(3S,5S,6S)-6-(3-Chlorophenyl)-6-hydroxy-5-methyl-3-thiomorpholine carboxylic acid,
3(3S,5R,6R)-6-(3-Chlorophenyl)-6-hydroxy-5-methyl-3-thiomorpholine carboxylic acid,
41-(3-chlorophenyl) propane-1,2-dione.
Inject reference solution (b), (d) and (e). The test is not valid unless the resolution between the peaks due to bupropion hydrochloride related compound F and bupropion hydrochloride related compound C is not less than 1.3 and peak due to bupropion hydrochloride related compound C and 3-chlorobenzoic acid is not less than 1.3 in the chromatogram obtained with reference solution (b) and relative standard deviation for replicate injections is not more than 10.0 per cent in the chromatogram obtained with reference solution (e).
For 100 mg or less —
Inject reference solution (c), (e) and the test solution (a) or (b). In the chromatogram obtained with the test solution (a) or (b), the area of the peak due to bupropion amine is not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.3 per cent), the area of the peak due to S,S,S-thiomorpholine derivative is not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (1.0 per cent), the area of the peak due to S,R,R-thiomorpholine derivative is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.5 per cent), the area of the peak due to bupropion related compound F is not more than 6.0 times the area of the principal peak in the chromatogram obtained with reference solution (e) (1.2 per cent), the area of the peak due to bupropion related compound C is not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.3 per cent), the area of the peak due to 3- chlorobenzoic acid is not more than 0.15 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.3 per cent), the area of the peak due to bupropion dione derivative is not more than 2.0 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.4 per cent). The area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (e) (0.2 per cent). The sum of areas of all the secondary peaks is not more than 16 times the area of the principal peak in the chromatogram obtained with reference solution (e) (3.2 per cent).
For 150 mg or more —
Inject reference solution (c), (e) and the test solution (a) or (b). In the chromatogram obtained with the test solution (a) or (b), the area of the peak due to bupropion amine is not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.3 per cent), the area of the peak due to S,S,S-thiomorpholine derivative is not more than 7.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (1.5 per cent), the area of the peak due to S,R,R-thiomorpholine derivative is not more than 2.0 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.4 per cent), the area of the peak due to bupropion related compound F is not more than 11.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (2.3 per cent), the area of the peak due to bupropion related compound C is not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.3 per cent), the area of the peak due to 3- chlorobenzoic acid is not more than 0.15 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.3 per cent), the area of the peak due to bupropion dione derivative is not more than 2.0 times the area of the principal peak in the chromatogram obtained with reference solution (e) (0.4 per cent). The area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (e) (0.2 per cent). The sum of areas of all the secondary peaks is not more than 16.5 times the area of the principal peak in the chromatogram obtained with reference solution (e) (3.3 per cent).
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2.4.14).
Solvent mixture (a), mobile phase (a) and (b), test solution (a) or test solution (b) describe under related substances.
Reference solution (f). A 0.002 per cent w/v solution of bupropion hydrochloride C RS [1-(3-chlorophenyl)-2-hydroxypropan-1-one] and 0.02 per cent w/v solution ofbupropion hydrochloride F RS [1-(3-chlorophenyl)-1-hydroxypropan-2-one] in methanol. Dilute 10.0 ml of this solution to 100.0 ml with solvent mixture (a).
Reference solution (g). A 0.06 per cent w/v solution of bupropion hydrochloride RS in the solvent mixture (a).
Inject reference solution (f) and (g). The test is not valid unless the resolution between the peaks due to bupropion hydrochloride related compound F and bupropion hydrochloride related compound C is not less than 1.3 in the chromatogram obtained with reference solution (f). The tailing factor is not more than 1.9 and the relative standard deviation for replicate injections is not more than 1.5 per cent in the chromatogram obtained with reference solution (g).
Inject reference solution (g) and the test solution (a) or (b).
Calculate the content of C13H18ClNO,HCl in the tablets.
Storage. Store protected from light, moisture and at controlled room temperature.