Scale industrial crystallization

Crystallization from solution often has to overcome serious limitations in bulk diffusion, particularly in large-scale industrial crystallizers. These limitations have been addressed in a number of formats. 

Crystallization, in the early years, was considered more an art than a science. Chapter 18 by Wieckhusen from Novartis outlines an excellent step-by-step tutorial to achieve control in large-scale industrial crystallizations. Blackmond and colleagues from Imperial College, London, UK,... 

In large-scale industrial crystallization processes, the most commonly used classification device is a hydrocyclone. The advantages of the hydrocyclone are its high capacity within a small equipment volume and an easily adjustable cutting size by the control of the feed-flow rate and the ratio of the up-flow to the down-flow. The fluid bed or elutriation leg is another method often used for classification in crystallization processes. With the elutriation leg, the feed or clear solution is fed from the bottom of the elutriation leg. The up-flow velocity is set based on the settling velocity of the cutting size... 

The products from a number of large-scale industrial crystallizers of the forced-circulation and DTB types have been reported (Bennett, 1962) to have... 

A particularly interesting feature of industrial crystallization systems is the relatively wide range of particle sizes encountered. Particle sizes range over several orders of magnitude from the sub micron (nanometers) to several millimetres or more, i.e. from colloidal to coarse . Such particles comprise a large part of the world on a human scale and a great source of industrially generated wealth. 

A tank crystallizer is the simplest type of industrial crystallizing equipment. Crystallization is induced by cooling the mother liquor in tanks, which may be agitated and equipped with cooling coils or jackets. Tank crystallizers are operated batch-wise and are generally used for small-scale production. 

Subtilisins are a family of serine proteases, the most important members of which are subtilisin Carlsberg (from Bacillus licheniformis) and subtilisin BPN (from Bacillus amyloliquefaciens)luoK Both enzymes are alkaline proteases with a pH optimum of 6-9. Because of their industrial importance, both subtilisin Carlsberg and subtilisin BPP have been studied intensively and are produced on a large scale. The crystal structures of both subtilisins have been determined1821. Directed evolution and site-directed mutagenesis and chemical modification of subtilisin were carried out in order to influence the stability, activity and enantioselectivity of the enzyme, in particular in organic solvents11111. As in the case of other enzymes,... 

Scale-Up of Industrial Crystallization Processes—Mission Impossible .311... 

SCALE-UP OF INDUSTRIAL CRYSTALLIZATION PROCESSES—MISSION IMPOSSIBLE ... 

A considerable amount of skepticism naturally is expressed by crystallization practitioners concerning the unbridled nse of parameters generated in well-controlled small-scale equipment to predict performance of industrial-scale crystallizers. Many factors contribute to the nonideal behavior of industrial crystallizers, and not all can be easily explained. 

The "natural" shape or habit of a crystal obtained in the medium from which it is crystallized is of minus) importance in designing an industrial-scale ciystallizer. Crystal habit is also of extrema interest to crystallization thcorisia, Many anicles have been writtno describing variables ther affect natural habit, and)... 

An obvious example is the surface-to-volume ratio, the value of which decreases with scale-up. Subsequently, high cooling rates can only be maintained in large-scale industrial practice if the jacket temperature is decreased substantially. This decrease may critically affect the nucleation rate however, as solution temperatures at and close to the crystallizer wall are also lowered, potentially enhancing primary or secondary nucleation in this region, the decrease may then cause crusting on the vessel walls. 

---