METHOD FOR PRODUCING LARGE-SIZED ISOXAZOLINE PARTICLES Russian patent published in 2023 - IPC C07D261/04 B01D9/00 B01D21/28 A61K31/42 A61P33/00 

FIELD: pharmaceuticals.

SUBSTANCE: group of inventions relates to methods for obtaining particles of an isoxazoline compound, where the isoxazoline compound is a compound of formula (I) where R¹ = halogen; n = 2; R² = C₁-C₃ haloalkyl; T = ring structure: 6-membered, which is substituted with one radical Y; Y=methyl; Q = X-NR³R⁴; X=CO; R³ = haloethylaminocarbonylethyl, R⁴ = hydrogen; or a salt thereof, wherein one embodiment of the method comprises the following: a) dissolving an isoxazoline compound in a solvent in a crystallizer, the solubility of the isoxazoline compound in a solvent being temperature dependent to obtain a batch of solution of the isoxazoline compound; b) initiating crystallization by i) cooling the crystallizer to supersaturation, or ii) vibrating the crystallizer, or iii) adding an isoxazoline compound seed to the crystallizer, or iv) a combination of two or more of the above; c) removing a part of the batch, heating the removed part until the particles of the isoxazoline compound are completely dissolved in the solvent and returning the resulting solution of the isoxazoline compound to the crystallizer; where the return rate is equal to the removal rate and ranges from 0.25 to 0.75 batch volume per hour; and where the batch volume is the volume of the isoxazoline compound solution obtained at step a); and d) cooling the crystallizer to obtain particles of an isoxazoline compound with an average thickness measured by scanning electron microscopy (SEM) of more than 10 μm and a volume-weighted average median diameter (d50) measured with an apparatus using the static light scattering method, in the range from 75 to 120 microns, and where the median particle diameter (d50) decreases by not more than 40% when quantitatively determining mechanical elasticity by determining the particle size distribution by increasing the dispersion pressure from 1 to 3 bar (from 100 to 300 kPa); in which the solvent is isopropanol; and in which the mold in step b is heated to a temperature above 60°C.

EFFECT: group of inventions provides for the development of a method of obtaining large particles of an isoxazoline compound.

22 cl, 17 dwg, 2 tbl, 5 ex