Patent Application
20080044462
Bupropion base can be prepared as described in U.S. Pat. Nos. 6,280,763, 6,312,716 and 6,582,737. In one embodiment, 1.2 g bupropion HCl is dissolved in 20 ml of distilled water to which 0.1 N NaOH is added until the pH is about 12. The mixture is extracted with 20 ml of diethyl ether followed by centrifugation. The ether phase containing the bupropion base is separated and the remaining aqueous phase is extracted three times with 80 ml diethyl ether. The ether phases are combined and dried (removal of residual water) over 15 g anhydrous K2CO3, filtered, and the ether is removed via evaporation. The bupropion base is stored under nitrogen gas in a tight bottle in the dark.
The modified procedure of bupropion base preparation is conducted under an inert atmosphere. In this procedure, concentrated ammonium hydroxide solution is used to convert bupropion HCl into bupropion base, the base is extracted three times with diethyl ether and the combined ether phases are dried over sodium sulfate. The solvent is removed under slightly reduced pressure at a water bath temperature of 30° C. The bupropion base is stored under nitrogen gas in a tight bottle in the dark.
Several potential stabilizers of bupropion base were evaluated for their ability to prevent discoloration of bupropion-containing patch prototypes. Patch prototype discoloration was used as an indicator of bupropion base stability. The following stabilizers at 0.003% (w/w) were examined: BHA, Vitamin A palmitate, Ascorbyl palmitate, and Vitamin E succinate. Sodium metabisulfite was examined at 0.001% (w/w). The patch prototypes underwent a three step drying process under the following conditions: 15minutes at 25° C., 15 minutes at 40° C. and 15 minutes at 80° C. The bupropion-containing matrices were sealed into pouches and stored for 72 hours at 60° C. in the oven.
Upon the completion of stability study, the pouches were opened and densitometric reflection color measurements were performed using a Techkon CP 230 color measurement system. It was found that while the placebo matrix was completely colorless, even freshly prepared bupropion base containing matrices showed a slight yellow color. The intensity of the color was 4-5 fold higher than that of placebo after 72 hours at 60° C. for all samples tested.
Bupropion base solution in diethyl ether is prepared as described in Example 1. An equimolar solution of stearic acid in diethyl ether will be added dropwise over about 3 hours to a magnetically stirred solution of bupropion base. The mixture will be stirred overnight at ambient temperature. The solvent will be removed under slightly reduced pressure at a water bath temperature of 30° C. The bupropion stearate will be stored in a tight bottle in the dark. The structure of this material will be confirmed by 1H NMR (CDCl3), mass spectrometry, elemental analysis and this layer chromatography (TLC).
This application claims the benefit of the priority of U.S. provisional application 60/789,635, filed Apr. 6, 2006.
| Number | Date | Country | |
|---|---|---|---|
| 60789635 | Apr 2006 | US |
