NDA
20-358: WELLBUTRIN® SR tablets
Figures 1-5 APPENDIX III). The linear regression equations (mean % absorbed in vivo versus mean % release in vitro) obtained for the three tablet strengths in the different dissolution media are as follows:
|
Medium |
50
mg |
100
mg |
150
mg |
|
0.1N
HCL |
Whited out |
||
|
pH
4.5* |
|||
|
Water |
|||
|
pH7.5* |
|||
|
Water# |
|||
*(Phosphate
buffer) (y
– mean % absorbed, x = mean % dissolved)
#(Pooled
Data for the three strengths)
Generally,
it was observed that in vitro release was about 10% to 28% greater than
the corresponding in vivo absorption. The slopes of the lines were close to unity when 0.1N HCL,
water, and pH 4.5 phosphate buffer were used as the dissolution medium.
The sponsor used the regression equations in water for the 150 mg SR tablet, along with the lower and upper limit of release specification (for the 1050 mg strength) to predict steady state bupropion plasma concentrations (as 150 mg given Q12h) – Figure 6, APPENDIX III. The predicted plasma concentrations were compared to that observed in the multiple-dose bioequivalency Study No. 206 involving the 150 mg SR tablet. The predicted bupropion concentration for the 150 mg SR tablet obtained in Study No. 206.
COMMENTS:
(To
the Medical Officer)
1)
The
150 mg bupropion HCL sustained release (SR) tablet (highest strength) given
twice daily (q12h) was found to equivalent to the 100 mg WELLBUTRIN® immediate
release (IR) tablet given three times a day (as 6,h, 6h, and 12 h dosings).
2)
Both
the 50 mg and the 100 mg bupropion HCL SR tablets were found to be equivalent
to the 150 mg bupropion HCL SR tablet when administered in equal single oral
doses of 300 mg.
3)
The
effect of food on WELLBUTRIN SR tablets (150 mg, highest strength), does not
appear to be clinically significant.
11
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