Acetate salt of buprenorphine and methods for preparing buprenorphine
The present disclosure provides acetate salts of buprenorphine, and its anhydrates, solvates, hydrates, and crystalline forms thereof, where the acetate salts of buprenorphine are essentially free of impurities. The disclosure further provides method of preparing the acetate salts, buprenorphine free base prepared from the acetate salts, other salts prepared from the free base, and pharmaceutical compositions thereof essentially free of impurities.
1. A buprenorphine free base composition, comprising at least about 98 wt % buprenorphine free base and 0.10 wt % or less of a compound of formula (12)
and 0.10 wt % or less of a compound of formula (13)
2. The buprenorphine free base composition of claim 1 , comprising at least about 99.5 wt % buprenorphine free base.
3. The buprenorphine free base composition of claim 1 , wherein the amount of the compound of formula (13) is about 0.05 wt % or less of the buprenorphine free base composition.
4. The buprenorphine free base composition of claim 3 , wherein the amount of the compound of formula (12) is about 0.08 wt % or less of the buprenorphine free base composition.
5. The buprenorphine free base composition of claim 3 , wherein the amount of the compound of formula (12) is between about 0.05 wt % and about 0.10 wt % of the buprenorphine free base composition.
6. The buprenorphine free base composition of claim 3 , wherein the amount of the compound of formula (12) is between about 0.05 wt % and about 0.08 wt % of the buprenorphine free base composition.
7. The buprenorphine free base composition of claim 6 , wherein the compound of formula (13) is not detected by HPLC analysis.
8. A pharmaceutical composition comprising the buprenorphine free base composition of claim 1 and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is formulated for oral administration.
10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is formulated as a tablet, a capsule, a gelcap, a caplet, a lozenge, an aqueous or oily solution, a suspension, a granule, a powder, an emulsion, a syrup, a quick dissolving tablet, a quick dissolving strip, or an elixir.
11. A transdermal patch comprising the pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprising the buprenorphine free base composition and the pharmaceutically acceptable carrier is contained in a reservoir or a matrix.
12. A buprenorphine free base composition, comprising buprenorphine free base and a total amount of impurities of about 0.25 wt % or less, wherein the buprenorphine free base composition comprises 0.10 wt % or less of a compound of formula (12):
and 0.10 wt % or less of a compound of formula (13):
13. The buprenorphine free base composition of claim 12 , wherein the amount of the compound of formula (13) is about 0.05 wt % or less of the buprenorphine free base composition.
14. The buprenorphine free base composition of claim 13 , wherein the amount of the compound of formula (12) is between about 0.05 wt % and about 0.08 wt % of the buprenorphine free base composition.
15. The buprenorphine free base composition of claim 14 , wherein the total amount of impurities is between about 0.05 wt % and about 0.15 wt %.
16. The buprenorphine free base composition of claim 14 , wherein the compound of formula (13) is not detected by HPLC analysis.
17. A pharmaceutical composition comprising the buprenorphine free base composition of claim 12 and a pharmaceutically acceptable carrier.
18. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is formulated for oral administration.
19. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is formulated as a tablet, a capsule, a gelcap, a caplet, a lozenge, an aqueous or oily solution, a suspension, a granule, a powder, an emulsion, a syrup, a quick dissolving tablet, a quick dissolving strip, or an elixir.
20. A transdermal patch comprising the pharmaceutical composition of claim 17 , wherein the pharmaceutical composition comprising the buprenorphine free base composition and the pharmaceutically acceptable carrier is contained in a reservoir or a matrix.