FIELD: pharmaceuticals.
SUBSTANCE: crystalline polymorphic form of 6-fluoro-9-methyl-9H-β -carboline of Formula (I), wherein the crystalline polymorph has an X-ray powder diffraction pattern containing peaks at 2-theta angles of 11.3, 17.1, 17.6, 18.0, 22.5, 23.2 and 29.4 degrees with deviation± 0.2 degrees. The invention also relates to a pharmaceutical composition for the treatment and/or prevention of hearing impairment, dizziness or vestibular disorder, containing a crystalline polymorphic form of 6-fluoro-9-methyl-9H-β -carboline according to the invention together with at least one pharmaceutically acceptable carrier, excipient, and/or diluent. Crystalline polymorphic form of 6-fluoro-9-methyl-9H-β-carboline of Formula (I) is prepared by A1) providing 6-fluoro-9-methyl-9H-β-carboline of Formula (I); B1) dissolution of 6-fluoro-9-methyl-9H-β-carboline in a mixture of a polar solvent and a non-polar solvent; or dissolving 6-fluoro-9-methyl-9H-β-carboline first in a polar solvent and adding a non-polar solvent to the resulting solution 6-fluoro-9-methyl-9H-β-carboline in a polar solvent, where the polar solvent is dichloromethane, acetone, isopropanol or a mixture thereof, or a mixture with water, and the non-polar solvent is methyl tert-butyl ether, n-heptane, cyclohexane or a mixture thereof, and the ratio of polar solvent and non-polar solvent is in the range from 1:2 to 1:10; and concentration of 6-fluoro-9-methyl-9H-β-carboline in a mixture of polar solvent and non-polar solvent is in the range from 50 mm to 200 mm; C1) heating a solution or suspension of 6-fluoro-9-methyl-9H-β-carboline to temperatures ranging from 40°C up to 100°C; D1) stirring the resulting solution for 10 minutes at the same temperature; E1) cooling the resulting solution to a temperature in the range from -10°C to +30°C to obtain the crystalline polymorphic form 6-fluoro-9-methyl-9H-β-carboline; and F) isolating crystalline polymorphic form B 6-fluoro-9-methyl-9H-β -carboline of Formula (I).
(I)
EFFECT: stable crystalline form of 6-fluoro-9-methyl-9H-β-carboline, for the treatment and/or prevention of hearing impairment, dizziness or vestibular disorders.
14 cl, 16 dwg, 6 tbl, 9 ex
