Oscillatory Mixing for Crystallization of High Crystal Perfection Pharmaceuticals

Abstract

In-situ Atomic Force Microscopy and Laser Optical Microscopy studies on a fixed single crystal growth, showed that the change of the direction of solution and its relative velocity with respect to the faces of growing crystal, are critical parameters for the minimization of the interfacial instabilities and, in turn, to the structural quality of a crystal. These findings were applied and tested in oscillatory baffled batch crystallizer (OBBC) precipitation experiments, in which, apart from hydrodynamics, all external conditions such as initial supersaturation, crystallization temperature and power density were kept constant. The physical properties (size distribution, surface characteristics, micro-strain content) of the precipitates were characterized by laser light scattering, scanning electron microscopy (SEM), and powder X-ray diffraction, respectively. The analysis of obtained results shows clearly that particles precipitated in OBBC are of significantly higher quality than those produced in conventional mixing using impeller driven batch crystallizer (IDBC). A computational fluid dynamics (CFD) software package, Fluent 5, was used to model dynamical fluid patterns in IDBC and OBBC. The modelling helped to get better appreciation for being able to precipitate particles of considerably higher perfection in OBBC than in IDBC. Also, it accounts for a high degree of equivalency of hydrodynamic conditions that a particle experiences when it grows in OBBC compared to those of a fixed crystal with interchangeable flow direction.