Process for the preparation of polymorph form b of treprostinil diethanolamine salt

• Main Authors: KARDOS, ZSUZSANNA, RITZ, IMOLA, HORTOBAGYI, IREN, VARGA, ZOLTAN, JUHASZ, IMRE, LASZLOFI, ISTVAN
• Format: Patent
• Language: Chinese; English
• Published: 11.12.2023
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY

The invention relates to a robust and reproducible process for the preparation of polymorph form B of treprostinil diethanolamine salt, comprising the following steps: a. treprostinil is dissolved in methanol, b. to the solution of step a) diethanolamine or its methanol solution is added, c. the reaction mixture of step b) is agitated till dissolution, d. when salt formation is completed in step c), first portion of an aprotic solvent is added to the solution, e. the solution of step d) is filtered to remove insoluble impurities, f. the filtrate of step e) is seeded with polymorph form B of treprostinil diethanolamine salt, g. to the crystal suspension obtained in step f) a second portion of the aprotic solvent is added, h. the suspension of step g) is agitated until crystallisation is completed, i. the crystals are separated, washed and dried.