Process to prepare treprostinil, the active ingredient in Remodulin®
This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil.
1. A pharmaceutical batch consisting of treprostinil or a salt thereof and impurities resulting from (a) alkylating a benzindene triol, (b) hydrolyzing the product of step (a) to form a solution comprising treprostinil, (c) containing the solution comprising treprostinil from step (b) with a base to form a salt of treprostinil, (d) isolating the salt of treprostinil, and (e) optionally reacting the salt of treprostinil with an acid to form treprostinil, and
wherein the pharmaceutical batch contains at least 2.9 g of treprostinil or its salt.
2. The pharmaceutical batch of claim 1 , which has been dried under vacuum.
3. A pharmaceutical product comprising a therapeutically effective amount of treprostinil from a pharmaceutical batch as claimed in claim 1 .
4. A pharmaceutical product comprising a therapeutically effective amount of a salt treprostinil from a pharmaceutical batch as claimed in claim 1 .
5. The product of claim 4 , wherein the salt is the diethanolamine salt of treprostinil.
6. A method of preparing a pharmaceutical product from a pharmaceutical batch as claimed in claim 1 , comprising storing a pharmaceutical batch of a salt of treprostinil as claimed in claim 1 at ambient temperature, and preparing a pharmaceutical product from the pharmaceutical batch after storage.
7. A method as claimed in claim 6 , wherein the salt of treprostinil is a diethanolamine salt.
8. A method of preparing a pharmaceutical batch as claimed in claim 1 , comprising (a) alkylating a benzindene triol, (b) hydrolyzing the product of step (a) to form a solution comprising treprostinil, (c) contacting the solution comprising treprostinil from step (b) with a base to form a salt of treprostinil, (d) isolating the salt of treprostinil, and (e) optionally reacting the salt of treprostinil with an acid to form treprostinil.
9. A method as claimed in claim 8 , wherein the salt of treprostinil is a diethanolamine salt.