par Rimez, Bart 
;Conté, Jennifer;Lecomte-Norrant, Edith ;Cognet, Patrick;Gourdon, Christophe;Scheid, Benoît
Référence Crystal growth & design, 18, 11, page (6440–6447)
Publication Publié, 2018
;Conté, Jennifer;Lecomte-Norrant, Edith ;Cognet, Patrick;Gourdon, Christophe;Scheid, Benoît Référence Crystal growth & design, 18, 11, page (6440–6447)
Publication Publié, 2018
Article révisé par les pairs
| Résumé : | The development of a continuous flow antisolvent crystallization protocol for a commercial active pharmaceutical ingredient, Brivaracetam, is described. To obtain increased nucleation kinetics of the desired crystalline form, solutions of Brivaracetam/isopropyl acetate are injected into micrometric tubing and mixed with a refrigerated antisolvent hexane. In this way very high supersaturation conditions are induced shortly after mixing. Residence times below 1 s after mixing in short tubular crystallizers are necessary for the desired, but thermodynamically unstable, crystals to grow. Arresting all crystal growth by immediate removal of the antisolvent containing mother liquors by continuous filtration or by casting the product onto filter paper prevents the formation of the thermodynamically stable pseudopolymorph - undesired due to its needle shape and solvated nature. Sufficient solid material output can be generated in order to be implemented in actual processing conditions if combined with suited continuous filtration units. |
