STABLE CRYSTALLINE MONOHYDRATE OF EPIRUBICIN HYDROCHLORIDE AND METHOD FOR PRODUCTION THEREOF Russian patent published in 2019 - IPC C07C29/78 C07H15/252 C07H1/00 

FIELD: medicine; pharmaceutical industry.

SUBSTANCE: present invention relates to crystalline epirubicin hydrochloride monohydrate applicable in medicine and pharmaceutics, characterized by: (i) water content in range of 2.7 % to 3.5 % (wt./wt.); (ii) a powder X-ray diffraction pattern comprising peaks at average diffraction angles (2Θ) 5.1°, 9.1°, 13.6°, 22.1°, 22.5° and 24.0° (each ± 0.2°); and (iii) in a method of producing, comprising: (a) adding at least a first solvent and at least a second solvent to epirubicin hydrochloride, wherein the first solvent is selected from a group consisting of 1-butanol, 2-butanol, isobutanol, tert-butanol and mixtures thereof; second solvent is selected from a group consisting of 1-propanol, isopropanol, ethanol and mixtures thereof; and volume ratio of first solvent to second solvent is in range from 1:1 to 2:1 (in vol. %); (b) bringing the water content in the solution obtained in step (a) to an amount in range of 8 % to 11 % (wt./wt.); (c) heating solution obtained at step (b) to temperature of 70 °C to 90 °C to ensure crystallisation; and (d) purifying crystals obtained in step (c); wherein the obtained crystalline epirubicin hydrochloride monohydrate is in form of particles which: (e) have an average diameter in range of 20 mcm to 50 mcm; (f) have particle size distribution, characterized in that at least 60 % and, in particular, at least 80 % of particles have size in the range of the following type: average diameter ± 20 %; and (g) contain residual solvents in amount of less than 0.5 % (wt./wt.).

EFFECT: disclosed is a novel crystalline monohydrate of epirubicin hydrochloride, characterized by improved thermal stability.

10 cl, 13 dwg, 5 tbl, 8 ex