Crystallization of Eflucimibe Drug in a Solvent Mixture: Effects of Process Conditions on Polymorphism

Autor:	Jean M. Autret, Sébastien Teychené, Béatrice Biscans
Rok vydání:	2004
Předmět:	Eflucimibe Chemistry Nucleation Analytical chemistry General Chemistry Condensed Matter Physics law.invention Crystallography Differential scanning calorimetry Polymorphism (materials science) law Metastability General Materials Science Solubility Crystallization Powder diffraction
Zdroj:	Crystal Growth & Design. 4:971-977
ISSN:	1528-7505 1528-7483
DOI:	10.1021/cg0341961
Popis:	Nucleation and metastability of the eflucimibe (S)-2',3',5'-trimethyl-4'-hydroxy-dodecylthiophenyl-acetanilide, a new acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) inhibitor, have been investigated according to a polythermal method. Eflucimibe exhibits two polymorphs, A and B, which crystallize simultaneously (concomitant polymorphs). The focus of this study was on the effect of the cooling rate, the initial concentration, and the seeds on metastability and polymorphism of eflucimibe. For nonseeded crystallization, it was found that the metastable zone width is large (primary nucleation) and fulfills well the linear relation between log ΔT max and log(dT/dt). In addition, the X-ray powder diffraction and differential scanning calorimetry analyses of the powder obtained show that the desired polymorph (pure A form) is difficult to obtain. On the contrary, for seeded experiments, the metastable zone width is significantly reduced (secondary nucleation) and the occurrence of polymorphism is controlled by seeding with the desired polymorph.
Databáze:	OpenAIRE
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