Crystallization by oscillatory and conventional mixing at constant power density

Abstract

The influence of mixing on crystallization processes has long been recognized. 1,2 The significance of mixing in crystallization is attributed to its role in the development and distribution of supersaturation, as well as the shear forces associated with the velocity field imposed by the impeller motion. These aspects of mixing are paramount to the quality of the precipitates (particles), often characterized by their crystal size distribution (CSD), surface characteristics, chemical purity, and crystalline imperfections (defect contents).Impeller driven stirred vessel has always been the prevalent choice in industrial crystallization for the production of pharmaceutics and specialty chemicals. However, in recent years, there has been an increasing interest in oscillatory flow mixing (OFM) as an attractive alternative mixing method, where intense eddy mixing is achieved in a baffled column by fluid oscillations. The attractiveness of this method lies in its performance enhancements over the conventional impeller-driven stirred vessel. This has been reported for processes such as heat-and mass-transfer, 3, 4 gas-liquid mixing, 5 and solid-liquid suspension. 6 However, a comparatively little attention has been paid to studies of this type of mixing on a possible improvement of the quality of precipitated particles, particularly in crystallization of low output high added-value products, such as pharmaceuticals, dyestuffs, catalysts and proteins.This article reports, for the first time, on the feasibility of OFM to improve the quality of pharmaceutical particles. For this purpose, paracetamol (4-acetaminophenol, 99ϩ%, Merck) was used as a model system.Experiments were conducted in parallel using a specially designed oscillatory baffled batch crystallizer (OBBC) ( Figure 1a) and classical impeller driven batch crystallizer (IDBC) (Figure 1b). The experiments were performed in both crystallizers under the same conditions of residence time ( r ϭ 30 min), temperature of crystallization (T ϭ 20°C), initial supersaturation (20 -50%), volume (500 mL) and power density (1.5 kW/m 3 ), but at distinctly different hydrodynamic environment. Paracetamol solution was prepared using the method previously described. 7 In each experiment, the solution was cooled down to a desired supersaturation before the agitation was initiated. The constant power density applied to both crystallizers was used as the reference criteria in these comparative studies. As we shall see later, this criteria is quite informative, because under the same conditions of residence time, temperature, initial supersaturation and volume of the two crystallizers, it enables us to assess the effectiveness of both mixing methods, in terms of quality of precipitated particles, for a given power input.The power density of IDBC was estimated by the PowerReynolds numbers correlation, which is common for most impeller driven systems; 8 while the power density of OBBC was estimated by the eddy acoustic model suitable for oscillations with frequencies and amplitudes in th...

Precipitation of hydroxyapatite at 37 °C in a meso oscillatory flow reactor operated in batch at constant power density

“…6,7 OFRs have been proved to result into significant enhancement in processes such as mass transfer, 8 particle mixing, and separation. 9 The basic concept of an OFR is the application of periodic fluid oscillations to a cylindrical column containing evenly spaced orifice baffles.…”

Oscillatory Flow Reactors (OFRs) for Continuous Manufacturing and Crystallization

“…Various crystal systems have been investigated in batch OBC platforms including paracetamol, 86,207,208 LGA 209-211 and sodium chlorate. 101,212,213 These studies (largely cooling crystallization) have included the effects of strain and shear on crystal suspensions and it is evident that the hydrodynamic environment of oscillatory mixing offers significant advantages, see Figure 15.…”

Development and characterisation of a cascade of moving baffle oscillatory crystallisers (CMBOC)

“…15,16 Crystal product quality can be particularly sensitive to the shear rate distribution during crystallisation. 17,18 Chew et al, 18 investigated the shear rate distribution and flow patterns in a stirred tank and in a moving baffle oscillatory crystalliser (MBOC) using computational fluid dynamics (CFD). They showed that in an MBOC, particles spend most of their time in the high shear regions whilst in the STC/MSMPR particles reside mainly in regions of low shear.…”