FIELD: pharmacology.
SUBSTANCE: invention relates to a new crystalline ηmodification of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride (fingolimod hydrochloride), its preparation method and application. This crystalline ηmodification can be used to prepare a pharmaceutical composition as an immunosuppressant for treatment of relapsing-remitting multiple sclerosis. Crystalline ηmodification of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride is characterized by the following set of interplanar distances (d, E) and their corresponding intensities (Irel., %) 25.199 - 100.00%; 12.569 - 4.46%; 8.362 - 8.20%; 7.171 - 3.10%; 6.705 - 1.11%; 5.841 - 5.94%; 4.985 - 2.63%; 4.572 - 4.96%; 4.341 - 9.98%; 4.176 - 8.11%; 4.073 - 4.77%; 3.867 - 4.27%; 3.776 - 2.14%; 3.581 - 3.02%; 3.393 - 3.34%; 3.185 - 1.07%; 3.069 - 2.65%; 3.005 - 1.17%; 2.991 - 1.13%; 2.842 - 1.25%; 2.802 - 1.56%, as well as by a set of endothermic effects on the DSC curve at temperatures (40.7±0.5)°C; (107.6±0.5)°C; (261.5±0.5)°C. A method for production of a crystalline ηmodification of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride includes freezing of an aqueous solution of fingolimod hydrochloride with a concentration of 0.5-8.0 wt %, at 25-100°C, acidified with hydrochloric acid to pH=(5-2), at a cooling rate of at least 60 deg/min and freeze dried. It is desirable to freeze dry the frozen solution of fingolimod hydrochloride at the following temperatures: (-43…-75)°C on the condenser; (-196…+50)°C on the product, and the residual pressure of (9-3)×10-2 Torr in the chamber, for 22-26 hours.
EFFECT: method allows to obtain a pure stable crystalline modification, which is a powder of white or almost white colour, odorless, water soluble, readily soluble in low molecular weight alcohols, dimethylsulfoxide, practically insoluble in acetonitrile.
4 cl, 6 dwg, 4 tbl, 4 ex
