FIELD: chemistry.
SUBSTANCE: invention relates to a nanoamorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione, a method for production thereof and use in pharmaceutical compositions, which can be used for treating immunological and/or oncological diseases. Amorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione is characterized by average particle size of 63.85±10 nm, glass transition temperature of 122.9±7 °C, crystallisation at temperature of 172.6±5 °C with specific thermal effect of 85.77±9 J/g and melting at temperature of 267.5±5 °C with specific heat effect of 149.8±15 J/g under conditions of differential scanning calorimetry at heating rate of 10 °C/min. Method of producing amorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione involves the following steps: loading (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione into a melt consisting of 40 or 20 g of D-fructose, 15 or 7.5 glactose monohydrate and 40 or 20 g urea at 55 °C; stirring at temperature of 55 °C; adding the obtained melt into water cooled to +7 °C; mixing; filtering the precipitate; preparation of suspension in water; stirring at temperature of 20 °C for about 1 hour; filtration; washing the precipitate with water on filter; drying to constant weight under vacuum at temperature of + 40 °C. Used at stage of loading into melt (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione is obtained by reduction of 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione with gray cast iron in the form of a chipped fraction in 50 % aqueous ethanol in the presence of hydrochloric acid.
EFFECT: amorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione is intended for treating immunological or oncological diseases.
6 cl, 10 dwg, 11 ex
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