B - Operations – Transporting – 01 – D
Patent
B - Operations, Transporting
01
D
B01D 9/00 (2006.01) B01D 9/02 (2006.01) B01F 5/02 (2006.01) B01F 11/02 (2006.01) B01F 13/10 (2006.01) B01J 4/00 (2006.01) B01J 19/00 (2006.01) B01J 19/10 (2006.01) B01J 19/18 (2006.01) C30B 7/00 (2006.01) C30B 7/10 (2006.01) B01F 7/00 (2006.01) B01F 13/00 (2006.01)
Patent
CA 2361078
A process is provided for the crystallization of pharmaceutical compounds by colliding a liquid jet stream (12) containing a pharmaceutical compound, such as Z-3-[1-(4-chlorophenyl)-1(4-methylsulfonylphenyl)methylene]-dihydrofuran-2- one or [R-(R*,R*)]-4-[2,4-Difluorophenyl-2-hydroxy-1-methyl-3-(1H-1,2,4- triazol-1-yl)propyl-4-thiazolyl]benzonitrile, and a solvent, such as dimethyl sulfoxide, with another liquid jet stream (14) containing an anti-solvent, such as water, within a crystallizer equipped with a mechanical stirrer (18) and at a velocity sufficient to achieve micromixing of the liquid streams. The micromixing of the liquids is subjected to ultrasonic energy (24) to promote the production of small crystals, 95 % of which have a diameter of less than one micron.
L'invention concerne un procédé de cristallisation de composés pharmaceutiques, ce procédé consistant notamment à faire entrer en collision un jet de liquide (12), qui contient un composé pharmaceutique tel que Z-3-[1-(4-chlorophényl)-1(4-méthylsulfonylphényl)méthylène]-dihydrofuran-2-one, ou [R-(R*,R*)]-4-[2,4-difluorophényl-2-hydroxy-1-méthyl-3-(1H-1,2,4-triazol-1-yl)propyl-4-thiazolyl]benzonitrile, et un solvant, par exemple du sulfoxyde diméthylique, avec un autre jet de liquide (14), lequel renferme un anti-solvant comme l'eau. Cette collision se produit à l'intérieur d'un cristalliseur équipé d'un agitateur mécanique (18), à une vitesse suffisante pour produire un micromélange des deux flux de liquide. Enfin, ce procédé consiste à soumettre ce micromélange de liquides à une énergie ultrasonore (24), afin de favoriser la production de petits cristaux, 95 % d'entre eux présentant un diamètre inférieur à un micromètre.
Kim Soojin
Lindrud Mark D.
Wei Chenkou
Bristol-Myers Squibb Company
Gowling Lafleur Henderson Llp
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