Influence of isomerism on recrystallization and cocrystallization induced by CO2 as an antisolvent

Christelle Harscoat-Schiavo (1) , Clémence Neurohr (1) , Sophie Lecomte (1) , Mathieu Marchivie (2) , Pascale Subra-Paternault (1)

1 CBMN - Chimie et Biologie des Membranes et des Nanoobjets
2 ICMCB - Institut de Chimie de la Matière Condensée de Bordeaux

Micronization, polymorphism, and cocrystal formation are well-known strategies to modify the characteristics of pharmaceutical ingredients. In this work, recrystallization induced by compressed CO2 as an antisolvent was investigated as a new way to produce aminosalicylate (ASA) polymorphs and cocrystals. Three ASA isomers were first recrystallized as single species. Isomerism has a particular influence on the product characteristics. The 5-ASA isomer was produced as micrometric spherical crystals with improved flow properties but no change in the crystal lattice was observed. 3-ASA recrystallized as micrometric spheres in a less dense crystal packing than that of the raw compound, and the 4-ASA isomer did not exhibit noticeable changes in the morphology or crystal lattice. Cocrystallization of each isomer with nicotinamide resulted in the production of an ASA:NCTA cocrystal only in the case of 4-ASA.

Domaines: Matériaux

Christelle Harscoat-Schiavo, Clémence Neurohr, Sophie Lecomte, Mathieu Marchivie, Pascale Subra-Paternault. Influence of isomerism on recrystallization and cocrystallization induced by CO2 as an antisolvent. CrystEngComm, 2015, 17 (29), pp.5410-5421. ⟨10.1039/c5ce00753d⟩. ⟨hal-01193299⟩