BILASTIN CRYSTALLINE FORMS AND THEIR PRODUCTION METHODS Russian patent published in 2022 - IPC C07D401/04 A61K31/454 A61P37/08 

FIELD: organic chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely to a method for the production of a hydrated crystalline Eta-form of 4-[2-[4-[1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]-1-piperidinyl)ethyl]-α,α-dimethyl-benzenacetic acid (bilastin). The method includes following stages: i) bilastin is dissolved in a mixture of water and acetonitrile at a temperature from 40 to 70°C; ii) a solution obtained at the stage i) is cooled to a temperature from 25 to 50°C; iii) a crystallization germ in the form of a hydrated crystalline Eta-form is introduced into a solution obtained at the stage ii), and the resulting solution is cooled to a temperature from 0 to 30°C for a time period necessary for crystallization; and iv) a crystalline form obtained at the stage iii) is dried at a reduced pressure at a temperature from 25 to 40°C until the water content is from 3.5 to 4% by weight, which is calculated by the Karl-Fischer method. The hydrated crystalline Eta-form of bilastin has an X-ray diffractogram that includes characteristic peaks at 8.4; 9.6; 12.2; 13.2; 15.1 and 19.2±0.2 degrees 2-theta, measured using an X-ray diffractometer with Cu-Kα radiation (1.5418 Å).

EFFECT: method is developed for the production of a hydrated crystalline Eta-form of bilastin with good physical and mechanical properties, such as stability and compressibility that allow for its easy use for the production of pharmaceutical compositions.

2 cl, 32 dwg, 2 tbl, 10 ex