Influence of Agitation and Fluid Shear on Primary Nucleation in Solution

Abstract

The influence of mechanical energy on primary nucleation of butyl paraben has been investigated through 1320 cooling crystallization experiments. The induction time has been measured at different supersaturations, temperatures, and levels of mechanical energy input, in two different flow systems. There is an overall tendency in the experiments that primary nucleation is promoted by increased input of mechanical energy. In small vials agitated by magnetic stir bars, the induction time was found to decrease with increasing agitation power input raised to 0.2 in the low agitation region. However, further increase in agitation leads to an increase again in the induction time. In a concentric cylinder apparatus of Taylor−Couette flow type, the induction time is inversely related to the shear rate. By fitting the parameters of the classical nucleation theory to experimental data, it is shown that the results can be explained as an influence on the pre-exponential factor. The treatment behind the pre-exponential factor is extended to account for the contribution of forced convection in a solution exposed to agitation and fluid shear. However, the analysis cannot verify that increased rate of mass transfer can explain the results. Alternative mechanisms are discussed based on a comprehensive review of the relevant literature. Shear-induced molecular alignment and in particular agitation-enhanced cluster aggregation are mechanisms that appear to deserve further attention. ■ INTRODUCTIONCrystallization processes are of significant importance to our society in industrial production of metallurgic and polymeric materials, and of inorganic and organic compounds; in the formation of shells and bone structures in nature; and in diseases such as the appearance of kidney stones and precipitates of amyloid proteins. In the industrial production of pharmaceutical compounds, crystallization is repeatedly used to separate and purify intermediates and is of major importance for the purification of the final product. Primary nucleation denotes the formation of a new particle in the solution, having a size sufficient for it to be thermodynamically stable at the prevailing conditions. Crystal nucleation has a governing influence on product properties and robustness of the process but is the mechanism of crystallization that is the least understood. This leads to significant problems in the design, operation, and control of industrial processes. Nucleation behavior is known to be unreliable and case sensitive. Because of this, industrial processes are developed by trial and error, and they often lack sufficient robustness. Sometimes lack of reproducibility requires rework or even disposal of the batch. The slow development of the fundamental understanding of primary nucleation is due to the nanoscale size range, the very strong nonlinear dependence on the supersaturation, and the significant stochastic component.The earliest evidence on the effect of mechanical stimulus on primary nucleation can be traced to the beginning of the 20th cent...

Influence of Agitation and Fluid Shear on Nucleation of m-Hydroxybenzoic Acid Polymorphs

“…Similar precautions to ensure reproducibility within the stochastic variability were undertaken as for the vial experiments. It was shown in a previous study 3 that the time required to effect 95% of the total temperature change under conditions similar to those of the present work is less than 6 min, and in 9 min the target temperature has been reached to within ±0.2°C.…”

“…For the Taylor−Couette experiments, average and maximum shear rates are calculated in our previous study. 3 Treating the agitation in the vials as if the stir bar is suspended from a rotating shaft, the energy transferred by the stir bar and the average shear rate in the vial experiments have been calculated in the previous study. 3 A rough estimate of the maximum fluid shear rate in the vial experiments is 150N, as for a turbine-stirred tank.…”

“…The Taylor−Couette flow system used, described in detail elsewhere, 3 is shown in Figure 4b. The setup features a sealed, cylindrical glass shell (diameter 50 mm, height 150 mm) with a rotating inner cylinder.…”

“…Although the vial experiments can be performed in large numbers, the flow conditions are complex and poorly controlled; the fluid dynamic conditions and shear rates are very nonuniform and the shearing conditions between the stir bar and the bottom of the vial are difficult to characterize. To study a case of simpler fluid dynamics, an apparatus with two concentric cylinders, called a Taylor−Couette flow system, has also been used, 3 allowing the generation of a more uniform shear stress in the solution. In each setup, the induction time for nucleation and the polymorphic outcome has been investigated at different levels of supersaturation, temperature and agitation/shear.…”

Influence of Agitation on Primary Nucleation in Stirred Tank Crystallizers

“…3 An important issue in scaling up of crystallization processes or introduction of changes to processing conditions involves the effect of altered agitation conditions on nucleation. In a previous contribution, 4 the literature on the influence of agitation and fluid shear on primary nucleation was reviewed in an attempt to summarize the development since the earliest publications on the subject in the beginning of the 20 th century. With few exceptions very little systematic work has been done, and the overall knowledge of the underlying principles and mechanisms is poor.…”