METHOD OF PRODUCING BORTEZOMIB LYOPHILIZATE AND A PHARMACEUTICAL COMPOSITION CONTAINING BORTEZOMIB IN FORM OF A STABLE LYOPHILIZED PRODUCT OBTAINED BY SAID METHOD Russian patent published in 2019 - IPC A61K9/19 A61K31/4965 A61K31/69 A61K47/26 A61P35/00 

FIELD: technological processes.

SUBSTANCE: invention relates to a method for producing bortezomib lyophilizate. Method involves the following steps: a) preliminary multiple recrystallisation of the bortezomib substance in methylene chloride, or methanol, or acetone, or ethyl acetate by dissolving the bortezomib substance in one of said solvents at ratio of 1:3 to 1:20 for about 15 minutes up to about 30 minutes at room temperature and after recrystallisation, subsequent evaporation of the obtained solution to dryness after complete dissolution of the bortezomib substance on the rotary evaporator under vacuum; b) preparing an aqueous solution of mannitol until complete dissolution thereof with concentration thereof in solution of 10–20 mg/ml for 0.5–5.0 h and maintaining pH from 4.0 to 5.0; c) preparing an aqueous solution of bortezomib in the aqueous solution of mannitol obtained in step (b), by dissolution of bortezomib substance in water solution of mannitol at 15–30 °C until complete dissolution thereof for less than 60 minutes to obtain a solution with a bortezomib concentration of 1.0–2.5 mg/ml at pH 5.0 to 6.5 and in an inert gas of nitrogen or argon; d) sterilizing filtration of solution from step (c) using filtration under vacuum or filtration under pressure of 0.1–0.6 MPa and dosing it into flasks; e) carrying out the product lyophilic drying from steps (d) in the lyophilic drying chamber in several steps; f) filling the lyophilic drying chamber with an inert gas, stopping the bottles and capping them. Pharmaceutical composition is also presented.

EFFECT: method according to the invention ensures production of a stable and highly purified end product – bortezomib lyophilizate, as well as monitoring of all stages of the process and conditions of their implementation.

5 cl, 1 tbl, 4 ex