FIELD: chemistry.
SUBSTANCE: invention relates to a novel salt nanosize weakly crystalline modification 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide (nilotinib) hydrochloride monohydrate. Nilotinib is used as an anti leucaemia cytostatic drug during therapy of cancerous diseases. The nanosize weakly crystalline modification is characterised by the following set of interplanar distances (d, E) and respective intensities (Iot, %) 14.70-27.8%; 12.94-19.4%; 11.43-22.2%; 7.474-26.4; 6.480-25.0%; 6.217-26.4%; 6.040-52.8%; 5.134-19.4%; 4.824-16.7%; 4.489-25.0%; 4.367-25.0%; 4.156-30.6%; 4.092-30.6%; 3.738-30.6%; 3.656-34.7%; 3.528-41.7%; 3.468-44.4%; 3.165-52.8%; 3.053-36.1%; 2.999-100%; 2.869-22.2%; 2.823-69.4%; 2.653-33.3%; 2.524-22.2%; 2.383-22.2%; 2.348-22.2%; 2.203-20.8%; 2.151-22.2%; 2.020-19.4%; 1.932-22.2%; 1.849-26.4%; 1.841-25.0%; 1.763-22.2%, three endothermic effects equal to (97.3±0.4) J/g at temperature of (92.6±0.5)°C, (54.5±0.4) J/g at temperature of (173.7±0.5)°C, (215.6±0.4) J/g at temperature of (273.4±0.5)°C, particle size of less than 150 nm, specific surface area of more than 30 m2/g and powder density in free filling of less than 0.024 g/cm3. A method of producing the modification includes preparing an aqueous solution of 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide hydrochloride monohydrate at 25-100°C, which is then frozen at a rate of not less than 60 degrees/minute, followed by removing the solvent by freeze-drying for 22-27 hours. The invention also relates to a pharmaceutical composition.
EFFECT: disclosed modification is 15-20 times more soluble than the existing modification A, which means it can be absorbed into the body over a shorter period and has high activity.
3 cl, 8 dwg, 1 tbl, 5 ex
